A Strategy for Synthesis of Nanosheets Consisting of Alternating Spinel Li4Ti5O12 and Rutile TiO2 Lamellas for High-Rate Anodes of Lithium-Ion Batteries.
Ultrathin dual phase nanosheets consisting of alternating spinel Li4Ti5O12 (LTO) and rutile TiO2 (RT) lamellas are synthesized through a facile and scalable hydrothermal method, and the formation mechanism is explored. The thickness of constituent lamellas can be controlled exactly by adjusting the mole ratio of Li:Ti in the original reactants. Alternating insertion of the RT lamellas significantly improves the electrochemical performance of LTO nanosheets, especially at high charge/discharge rates. As anodes in lithium-ion batteries (LIBs), the dual phase nanosheet electrode with the optimized phase ratio can deliver stable discharge capacities of 178.5, 154.9, 148.4, 142.3, 138.2, and 131.4 mA h g-1 at current densities of 1, 10, 20, 30, 40, and 50 C, respectively. Meanwhile, they inherit the excellent cyclic stability of pure spinel LTO and exhibit a capacity retention of 93.1% even after 500 cycles at 50 C. Our results indicate that the alternating nanoscaled lamella structure is a good alternative to facilitate the transfer of both the Li ions and electrons into the spinel LTO, giving rise to an excellent cyclability and fast rate performance. Therefore, the newly prepared carbon-free LTO-RT nanosheets with high safety provide a new opportunity to develop high-power anodes for LIBs.


Variability of Symbiodinium Communities in Waters, Sediments, and Corals of Thermally Distinct Reef Pools in American Samoa.
Reef-building corals host assemblages of symbiotic algae (Symbiodinium spp.) whose diversity and abundance may fluctuate under different conditions, potentially facilitating acclimatization to environmental change. The composition of free-living Symbiodinium in reef waters and sediments may also be environmentally labile and may influence symbiotic assemblages by mediating supply and dispersal. The magnitude and spatial scales of environmental influence over Symbiodinium composition in different reef habitat compartments are, however, not well understood. We used pyrosequencing to compare Symbiodinium in sediments, water, and ten coral species between two backreef pools in American Samoa with contrasting thermal environments. We found distinct compartmental assemblages of clades A, C, D, F, and/or G Symbiodinium types, with strong differences between pools in water, sediments, and two coral species. In the pool with higher and more variable temperatures, abundance of various clade A and C types differed compared to the other pool, while abundance of D types was lower in sediments but higher in water and in Pavona venosa, revealing an altered habitat distribution and potential linkages among compartments. The lack of between-pool effects in other coral species was due to either low overall variability (in the case of Porites) or high within-pool variability. Symbiodinium communities in water and sediment also showed within-pool structure, indicating that environmental influences may operate over multiple, small spatial scales. This work suggests that Symbiodinium composition is highly labile in reef waters, sediments, and some corals, but the underlying drivers and functional consequences of this plasticity require further testing with high spatial resolution biological and environmental sampling.


Giving voice to emerging science and theory for lesbian, gay, and bisexual people of color.
Lesbian, gay, and bisexual (LGB) people of color may experience multiple layers of oppression, as they often not only contend with the negative societal reactions to their sexual orientation but also may experience racial prejudice, limited economic resources, and limited acceptance within their own cultural community. Despite the range of psychosocial issues that may be encountered by this population, and the need to understand factors that promote resiliency and well-being, the empirical psychological literature has virtually ignored LGB people of color. This article provides general background regarding the empirical research needs and concerns regarding LGB people of color and introduces the articles included in this special issue. Recommendations for increasing research with LGB people of color are offered.


Characterization of the in vivo dynamics of medullary CD4+CD8- thymocyte development.
Our previous studies have defined a differentiation program followed by the newly generated single-positive (SP) thymocytes before their emigration to the periphery. In the present study, we further characterize the development of CD4SP cells in the thymic medulla using mainly intrathymic adoptive transfer assays. By analyzing the differentiation kinetics of the donor cells, which were shown to home correctly to the medullary region following adoptive transfer, we established the precursor-progeny relationship among the four subsets of CD4SP thymocytes (SP1-SP4) and demonstrated that the progression from SP1 to SP4 was unidirectional and largely synchronized. Notably, while the phenotypic maturation from SP1 to SP4 was achieved in 2-3 days, a small fraction of donor cells could be retained in the thymus for a longer period, during which they further matured in function. BrdU incorporation indicated that cell expansion occurred at multiple stages except SP1. Nevertheless, CFSE labeling revealed that only a limited number of cells actually divided during their stay in the medulla. As to the thymic emigration, there was a clear bias toward cells with increasing maturity, but no distinction was found between dividing and nondividing thymocytes. Collectively, these data not only provide solid evidence for a highly ordered differentiation program for CD4SP thymocytes, but they also illustrate several important features associated with the developmental process.


Racial density and the socioeconomic, demographic and health context in Brazilian cities in 2000 and 2010.
Racial density has not yet been explored in studies of racial inequalities in Brazil. Thisstudy identified categories of racial density in Brazilian cities and described the living and health context in these categories in 2000 and 2010, when demographic censuses were conducted. Ecological study which used skin color or race information from the last two censuses to calculate racial density (the ratio of people aggregated to the same racial group) of the Brazilian cities each year. Four categories of racial density (Brown; Mixed-race, predominantly black; White/Caucasian; and Mixed-race, predominantly white). Socioeconomic, demographic and health indicators were described to each category. The categories of racial density captured important inequalities throughout the census and also indicated the continuance of worse living and health conditions in the cities composed by Browns and mixed-race people, predominantly Black; better conditions were indicated in cities where White/Caucasians are predominant. The cities, composed mainly of Browns and mixed-race people, predominantly Black, presented younger age structure, worse human development indexes, greater social vulnerability, income concentration, infant and premature mortality (<65 years) and lower life expectancy in both censuses, as compared to other cities. Similarly to other countries, the racial density reflected inequalities in the Brazilian living and health context as well as a time lag among the cities. The categories of racial density may contribute to social epidemiology and race relations studies in Brazil.


Sinus barotrauma in divers.
Sinus barotrauma is a common occupational disease of divers, with the incidence of descent barotrauma approximately double that of ascent. Pain chronologically associated with the change of pressure is the most dominant symptom and is seen in 92% of the cases presented for treatment. The majority complain of a frontal distribution of pain, with ethmoidal and maxillary being much less significant. Epistaxis is the second commonest symptom, and may be the sole symptom in some ascent cases. A history of recent or past sinus barotrauma or upper respiratory tract pathology is very common. Clinical examination supports the evidence of upper respiratory tract pathology in many cases. The radiological signs of abnormality were present in over three quarters of the cases examined. Of these the maxillary sinus was affected in most cases, the frontal in approximately one quarter and the ethmoidal in less than a fifth. The pathology was more commonly that of mucosal thickening, but in 12% of cases there was a fluid level. It is noted that although symptoms were predominantly frontal, x-ray changes were most often present in the maxillary sinuses.


Super-Alarms with Diagnosis Proficiency Used as an Additional Layer of Protection Applied to an Oil Transport System.
In automated plants, particularly in the petrochemical, energy, and chemical industries, the combined management of all of the incidents that can produce a catastrophic accident is required. In order to do this, an alarm management methodology can be formulated as a discrete event sequence recognition problem, in which time patterns are used to identify the safe condition of the process, especially in the start-up and shutdown stages. In this paper, a new layer of protection (a Super-Alarm), based on the diagnostic stage to industrial processes is presented. The alarms and actions of the standard operating procedures are considered to be discrete events involved in sequences; the diagnostic stage corresponds to the recognition of the situation when these sequences occur. This provides operators with pertinent information about the normal or abnormal situations induced by the flow of the alarms. Chronicles Based Alarm Management (CBAM) is the methodology used in this document to build the chronicles that will permit us to generate the Super-Alarms; in addition, a case study of the petrochemical sector using CBAM is presented in order to build one chronicle that represents the scenario of an abnormal start-up of an oil transport system. Finally, the scenario's validation for this case is performed, showing the way in which, a Super-Alarm is generated.


RhoA protein expression in primary breast cancers and matched lymphocytes is associated with progression of the disease.
RhoA protein is over-expressed in breast cancer and other solid tumors and has been used in tumor biopsies as a quantitative tumor marker for progression, stage and prognosis in molecular detection strategies. Measuring protein markers in plasma or blood cells is preferred to tumor biopsies as it represents a minimally invasive, repeatable measurement that can be followed over time. In this study we evaluated the hypothesis that quantitative RhoA protein expression in circulatory lymphocytes is identically associated with the same tumor clinico-pathological features found in biopsies. RhoA protein levels were analyzed by Western blotting in circulating lymphocytes isolated from 52 consecutive patients with breast cancer and in 34 paired breast tumor biopsies from the same case study, and compared with the following clinico-pathological features of the patients: histological grade, tumor size, steroid receptor status, lymphonode status, proliferative activity and prognosis [Nottingham Prognostic Index (NPI)]. We observed that the level of circulatory, peripheral lymphocyte RhoA expression reflected that found in the matched biopsy of the same patient. Furthermore, similarly to previous reports regarding breast cancer tissue biopsies, the level of RhoA protein expression in both biopsies and in circulatory lymphocytes was positively associated with tumor size, grade, proliferative activity of the tumor biopsy and NPI, while there was no significant association of RhoA protein expression with either estrogen- or progesterone-receptor expression. Our study demonstrated that the association of lymphocyte RhoA protein expression with classical clinico-pathological parameters closely corresponded with that observed for RhoA protein expression in the tumor biopsies. We propose that measurement of RhoA expression in the circulatory lymphocytes of breast cancer patients can be used to predict breast cancer occurrence, progression and prognosis and may prove valuable in the management of cancer patients.


Safety and efficacy of laparoscopic cholecystectomy using monopolar electrocautery in the porcine model.
Recent reports suggest that laparoscopic laser cholecystectomy may become the preferred therapy for symptomatic cholelithiasis. To assess the efficacy and safety of this technique, using monopolar electrocautery instead of laser for the gallbladder dissection, laparoscopic cholecystectomy was performed on 11 pigs. Under general anesthesia, a pneumoperitoneum was established, and four sheaths were placed into the abdomen for introduction of instruments. Using video laparoscopic guidance, the cystic duct and artery were isolated, clipped, and divided. Monopolar electrocautery was used to dissect the gallbladder from its fossa. Five animals were sacrificed immediately, without visible evidence of injury to the bile ducts, liver, or intestine. The remaining six pigs were allowed to recover. One animal died 10 days postoperatively due to adhesive small bowel obstruction. The remainder survived in good health until sacrifice at 1 month. Histologic examination of the gallbladder bed and liver revealed no evidence of ongoing local hepatocyte destruction or chronic cholestasis. Cholangiography demonstrated the bile ducts to be intact. Mean (+/- SEM) total serum bilirubin (TB), alkaline phosphatase (AP), and glutamic oxalacetic transaminase (SGOT) at the time of sacrifice were similar to nonoperated swine (n = 10): TB, 0.12 +/- 0.02 versus 0.11 +/- 0.01 mg/dl; AP, 175 +/- 23 versus 162 +/- 10 IU/L; SGOT, 37 +/- 4 versus 55 +/- 7 IU/L, respectively (p > 0.05). We conclude that laparoscopic cholecystectomy can be performed using monopolar electrocautery without significant acute injury to the liver, bile ducts, or surrounding viscera. Furthermore, the porcine model can be utilized by surgeons to attain competence in this technique prior to instituting clinical application in humans.


Reverse transcriptase loop-mediated isothermal amplification assay for infectious hematopoietic necrosis virus in Oncorhynchus keta.
A reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay was developed for detecting infectious hematopoietic necrosis virus (IHNV) from chum salmon Oncorhynchus keta in South Korea with high specificity, sensitivity and rapidity. A set of 6 IHNV-specific primers was designed, based on the G-protein sequence of IHNV (PRT strain), recognizing 8 distinct sequences of the target RNA. The assay was optimized to detect IHNV at 63 degrees C for 30 min. The limit of detection was 0.01 fg of RNA extracted from IHNV-infected CHSE-214 cells, compared with 1.0 fg for nested RT-PCR. The applicability of this RT-LAMP assay was further tested by comparison with nested RT-PCR using field samples. Of 473 samples tested, 191 samples (40.38%) were IHNV-positive by RT-LAMP, whereas 162 samples (34.25%) were IHNV-positive by nested RT-PCR. These results indicate that, because of its high sensitivity and rapidity, the RT-LAMP assay is useful for early diagnosis of IHN.


Multiple hPOT1-TPP1 cooperatively unfold contiguous telomeric G-quadruplexes proceeding from 3' toward 5', a feature due to a 3'-end binding preference and to structuring of telomeric DNA.
Telomeres are DNA repeated sequences that associate with shelterin proteins and protect the ends of eukaryotic chromosomes. Human telomeres are composed of 5'TTAGGG repeats and ends with a 3' single-stranded tail, called G-overhang, that can be specifically bound by the shelterin protein hPOT1 (human Protection of Telomeres 1). In vitro studies have shown that the telomeric G-strand can fold into stable contiguous G-quadruplexes (G4). In the present study we investigated how hPOT1, in complex with its shelterin partner TPP1, binds to telomeric sequences structured into contiguous G4 in potassium solutions. We observed that binding of multiple hPOT1-TPP1 preferentially proceeds from 3' toward 5'. We explain this directionality in terms of two factors: (i) the preference of hPOT1-TPP1 for the binding site situated at the 3' end of a telomeric sequence and (ii) the cooperative binding displayed by hPOT1-TPP1 in potassium. By comparing binding in K+ and in Li+, we demonstrate that this cooperative behaviour does not stem from protein-protein interactions, but from structuring of the telomeric DNA substrate into contiguous G4 in potassium. Our study suggests that POT1-TPP1, in physiological conditions, might preferentially cover the telomeric G-overhang starting from the 3'-end and proceeding toward 5'.


Seasonal variation in the occurrence of late adverse skin reactions to iodine-based contrast media.
To study the possible seasonal effect in the occurrence of late adverse skin reactions to iodine-based contrast media (CM). Data on 4,875 adult patients followed for late adverse reactions after i.v. injections of iohexol or iopamidol, or intra-arterial injection of ioxaglate were retrospectively investigated with respect to the amount of global radiation vs. the occurrence of reactions. The information on these reactions was collected from questionnaires that were filled out by the patients (out-patients) or by nurses (in-patients). The follow-up time was 24 h. Fifty-two of 4,875 patients (1.07%) had experienced a late skin reaction (urticaria or rash); this number exceeds the reports on spontaneous occurrence of such reactions by a factor of 300. Most of the reactions in a known location occurred on sun-exposed areas of the body. A 2-month peak in the incidence of reactions (May to June) included 35% of all events (p<0.025) and a 3-month peak (April to June) 46% of all events (p<0.01). There was a significant rank correlation (r = 0.613, p<0.05) between the frequency of reactions and the mean amount of global radiation. This study demonstrates a seasonal variation in skin reactions after intravascular injection of iodine-based CM. The possible photosensitising effect of these drugs should be further studied.


Neighbourhood of domicile and hospital admissions in Auckland: is there a relationship?
The relationship between the health and equity index of socioeconomic status/need and hospital admission rates has been investigated. The index is based on an area's population characteristics, and has previously been used for determining service provision and to describe an area's health need. This study demonstrates a strong positive correlation (r = 0.88, 95% confidence intervals 0.75 to 0.94) between the index and standardised hospital admission rates in the Auckland urban area. This association validates the index as a proxy for morbidity, in as much as hospital admission rates measure morbidity, and supports suggestions for its use to alter interregional and intraregional resource allocation.


How to present a curriculum vitae.
At times, as for example when candlelight flickers on bottle and glasses, it is not unpleasant to look into a pair of warm and friendly eyes and respond to the words "Tell me about yourself." Completing a curriculum vitae (CV), however, is a less attractive proposition, especially when applying for an appointment. Even those who are fond of talking about themselves can find it difficult. Some find it embarrassing. Some, judging from the poorly presented data which frequently accompany applications even for senior posts, are unaware of the important part the CV plays in the selection process.


High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor.
Accurate optical reporting of electrical activity in genetically defined neuronal populations is a long-standing goal in neuroscience. We developed Accelerated Sensor of Action Potentials 1 (ASAP1), a voltage sensor design in which a circularly permuted green fluorescent protein is inserted in an extracellular loop of a voltage-sensing domain, rendering fluorescence responsive to membrane potential. ASAP1 demonstrated on and off kinetics of ∼ 2 ms, reliably detected single action potentials and subthreshold potential changes, and tracked trains of action potential waveforms up to 200 Hz in single trials. With a favorable combination of brightness, dynamic range and speed, ASAP1 enables continuous monitoring of membrane potential in neurons at kilohertz frame rates using standard epifluorescence microscopy.


Therapeutic liver repopulation for phenylketonuria.
Problems with long-term dietary compliance in phenylketonuria (PKU) necessitate the development of alternative treatment approaches. Therapeutic liver repopulation with phenylalanine hydroxylase (PAH)-expressing cells following hepatocyte or haematopoietic stem cell transplantation has been investigated as a possible novel treatment approach for PKU. Successful therapeutic liver repopulation requires both a stimulus for liver regeneration at the time of cell transplantation and a selective growth advantage for the PAH+ donor cells. Unfortunately, wild-type PAH+ hepatocytes do not enjoy any growth advantage over PAH- cells. Successful correction of hyperphenylalaninemia following therapeutic liver repopulation has been accomplished only in an animal model that yields a selective advantage for the donor cells. Haematopoietic stem cell (HSC)-mediated therapeutic liver repopulation has not been reported in any hyperphenylalaninemic system, and the success of HSC-mediated liver repopulation for PKU may be limited by the slow kinetics of this approach. If therapeutic liver repopulation is to be employed successfully in humans with PKU, an effective method of providing a selective growth advantage for the donor cells must be developed. If this can be achieved, liver repopulation with 10-20% wild-type hepatocytes will likely completely normalize Phe clearance in individuals with PKU.


Characterization of antibody 444 using chromatographically purified enantiomers of juvenile hormones I, II, and III: implications for radioimmunoassays.
Optically pure (> 99.5%) enantiomers of insect juvenile hormones (JH) I, II, and III were obtained by injection of racemic mixtures onto a chiral HPLC column using hexane:2-propanol (99.5:0.5) as the mobile phase. The enantiomers of JH III were the best resolved (R = 4.26), followed by those of JH II (R = 2.29) and JH I (R = 1.47). These purified natural and unnatural enantiomers were used to further characterize an antiserum (444) developed for JH radioimmunoassays (RIAs). Based on ED50 values generated using optically pure [methyl-3H]-10R,11S-JH II as a tracer, the natural isomers of JH I, JH II, and JH III were 30, 87, and 36 times more immunoreactive, respectively, than the unnatural isomers. When compared with the racemates, the natural isomers were approximately twice as immunoreactive. In competitive displacement studies where the natural enantiomers of the three JHs were compared, immunoreactivities were in the order JH II > JH I > JH III (ED50 = 109, 198, and 300, respectively). Availability of pure natural enantiomers of JH, both as tracers and competitors, should improve the sensitivity and accuracy of JH titer determinations made by RIA and facilitate various enzyme, binding protein, and receptor studies.


Characterization of a specific antiserum for mammalian collagenase from several species: immunolocalization of collagenase in rabbit chondrocytes and uterus.
A specific antiserum to rabbit bone collagenase was raised in a sheep and shown to react with collagenase from several mammalian species. This antiserum was used to demonstrate that only active collagenase binds to and can be immunolocalized on collagen fibrils and, by indirect immunofluorescence, the secretion of latent collagenase by stimulated rabbit chondrocytes and cells of the post-partum involuting rabbit uterus. The ionophore monensin was used to demonstrate intracellular accumulation of collagenase in the Golgi apparatus of both stimulated chondrocytes and involuting uterine cells. Collagenase was not detectable in either normal cartilage or non-gravid uterus. These results are discussed in relation to other studies of collagenase immunolocalization reported in the literature.


LIFE BEEF CARBON: a common framework for quantifying grass and corn based beef farms' carbon footprints.
Europe's roadmap to a low-carbon economy aims to cut greenhouse gas (GHG) emissions 80% below 1990 levels by 2050. Beef production is an important source of GHG emissions and is expected to increase as the world population grows. LIFE BEEF CARBON is a voluntary European initiative that aims to reduce GHG emissions per unit of beef (carbon footprint) by 15% over a 10-year period on 2172 farms in four large beef-producing countries. Changes in farms beef carbon footprint are normally estimated via simulation modelling, but the methods current models apply differ. Thus, our initial goal was to develop a common modelling framework to estimate beef farms carbon footprint. The framework was developed for a diverse set of Western Europe farms located in Ireland, Spain, Italy and France. Whole farm and life cycle assessment (LCA) models were selected to quantify emissions for the different production contexts and harmonized. Carbon Audit was chosen for Ireland, Bovid-CO2 for Spain and CAP'2ER for France and Italy. All models were tested using 20 case study farms, that is, 5 per country and quantified GHG emissions associated with on-farm live weight gain. The comparison showed the ranking of beef systems gross carbon footprint was consistent across the three models. Suckler to weaning or store systems generally had the highest carbon footprint followed by suckler to beef systems and fattening beef systems. When applied to the same farm, Carbon Audit's footprint estimates were slightly lower than CAP'2ER, but marginally higher than Bovid-CO2. These differences occurred because the models were adapted to a specific region's production circumstances, which meant their emission factors for key sources; that is, methane from enteric fermentation and GHG emissions from concentrates were less accurate when used outside their target region. Thus, for the common modelling framework, region-specific LCA models were chosen to estimate beef carbon footprints instead of a single generic model. Additionally, the Carbon Audit and Bovid-CO2 models were updated to include carbon removal by soil and other environmental metrics included in CAP'2ER, for example, acidification. This allows all models to assess the effect carbon mitigation strategies have on other potential pollutants. Several options were identified to reduce beef farms carbon footprint, for example, improving genetic merit. These options were assessed for beef systems, and a mitigation plan was created by each nation. The cumulative mitigation effect of the LIFE BEEF CARBON plan was estimated to exceed the projects reduction target (-15%).


Neglected Anterior Dislocation of the Elbow Joint: Case Report of a Rare Injury.
We present an unusual case of five months old neglected anterior dislocation of the right elbow joint in a 19-year old man. The patient had been initially treated by a traditional bone setter, but the elbow remained unreduced. He presented to us with pain, deformity and limited range of motion of his right elbow joint. Radiographs revealed an unreduced anterior dislocation of the right elbow joint. We describe the problems encountered during open reduction and rehabilitation and result one year after the operation with the patient having a stable elbow and a functional range of motion.


Risk of Infective Endocarditis in Patients with End Stage Renal Disease.
Endocarditis is a serious complication in patients treated with RRT. The study aimed to examine incidence and risk factors of endocarditis in patients with ESRD. The Danish National Registry on Regular Dialysis and Transplantation contains data on all Danish patients receiving renal replacement (hemodialysis, peritoneal dialysis, or kidney transplantation) for ESRD. Incidence of endocarditis was estimated for each RRT modality. Independent risk factors of endocarditis were identified in multivariable Cox regression models. From January 1st, 1996 to December 31st, 2012, 10,612 patients (mean age 63 years, 36% female) initiated RRT (7233 hemodialysis, 3056 peritoneal dialysis, 323 pre-emptive kidney transplantation). Endocarditis developed in 267 (2.5%); of these 31 (12%) underwent valve surgery. The overall incidence of endocarditis was 627 per 100,000 person-years in patients receiving RRT. Incidence was higher in patients receiving hemodialysis compared with those receiving peritoneal dialysis or kidney transplantation (1092 per 100,000 person-years, 212 per 100,000 person-years, and 85 per 100,000 person-years, respectively). Adjusted hazard ratios for endocarditis in patients receiving hemodialysis were 5.46 (95% confidence interval [95% CI], 3.28 to 9.10) and 0.41 (95% CI, 0.18 to 0.91) for kidney-transplanted recipients, respectively, as compared with patients in peritoneal dialysis. The incidence of endocarditis in hemodialysis recipients with central venous catheters was more than two-fold higher as compared with those with arteriovenous fistulas. Overall mortality, subsequent to endocarditis, was 22% in-hospital and 51% at 1 year. The first 6 months in RRT, aortic valve disease, and previous endocarditis were identified as significant risk factors of endocarditis. Patients receiving RRT have a high incidence of endocarditis, in particular during hemodialysis treatment using central venous catheters. The first 6 months in RRT, aortic valve disease, and previous endocarditis are significant risk factors for developing endocarditis.


Effects of propranolol on symptom and endocrine responses to pentagastrin.
Intravenous injections of CCK-B agonists, such as pentagastrin, produce symptoms of panic and potent activation of the human hypothalamic-pituitary-adrenal (HPA) axis. It is unclear whether these psychological and endocrine effects are mediated by similar or independent processes. Independence is supported by prior evidence that beta-adrenergic receptor blockade attenuates cardiovascular and symptom but not vasopressin responses to CCK-4. To further explore associations between somatic, emotional and endocrine responses to CCK-B agents, and potential beta-adrenergic mediating mechanisms, symptom and endocrine responses to pentagastrin were examined after propranolol pre-treatment. Cardiovascular, symptom, and endocrine (ACTH, cortisol, epinephrine) responses to pentagastrin were measured in 16 healthy adult subjects randomly assigned to receive propranolol or placebo pre-treatment. Propranolol significantly blocked the normal cardiac acceleration produced by pentagastrin, but did not reduce panic symptom or anxiety effects. It delayed and perhaps enhanced the cortisol response. No relationship between HPA and symptom responses following pentagastrin could be detected, though pre-pentagastrin cortisol was inversely related to post-injection panic symptom intensity. Endocrine, cardiovascular and symptom responses to pentagastrin appear to be separately mediated, as they did not change in concert in response to propranolol pre-treatment, nor were they correlated with one another. The results are consistent with the presence of inhibitory beta-adrenergic mediation of the HPA axis in humans. They support the hypothesis that the HPA response to pentagastrin is not secondary to the psychological stress of its side effects.


Local and Landscape Constraints on Coffee Leafhopper (Hemiptera: Cicadellidae) Diversity.
The intensification of agriculture drives many ecological and environmental consequences including impacts on crop pest populations and communities. These changes are manifested at multiple scales including small-scale management practices and changes to the composition of land-use types in the surrounding landscape. In this study, we sought to examine the influence of local and landscape-scale agricultural factors on a leafhopper herbivore community in Mexican coffee plantations. We sampled leafhopper (Hemiptera: Cicadellidae) diversity in 38 sites from 9 coffee plantations of the Soconusco region of Chiapas, Mexico. While local management factors such as coffee density, branches per coffee bush, tree species, and density were not important in explaining leafhopper abundance and richness, shade management at the landscape level and elevation significantly affected leafhoppers. Specifically, the percentage of low-shade coffee in the landscape (1,000-m radius surrounding sites) increased total leafhopper abundance. In addition, Shannon's diversity of leafhoppers was increased with coffee density. Our results show that abundance and diversity of leafhoppers are greater in simplified landscapes, thereby suggesting that these landscapes will have higher pest pressure and may be more at-risk for diseases vectored by these species in an economically important crop.


A Real-Time Mobile Intervention to Reduce Sedentary Behavior Before and After Cancer Surgery: Usability and Feasibility Study.
Sedentary behavior (SB) is common after cancer surgery and may negatively affect recovery and quality of life, but postoperative symptoms such as pain can be a significant barrier to patients achieving recommended physical activity levels. We conducted a single-arm pilot trial evaluating the usability and acceptability of a real-time mobile intervention that detects prolonged SB in the perioperative period and delivers prompts to walk that are tailored to daily self-reported symptom burden. The aim of this study is to develop and test a mobile technology-supported intervention to reduce SB before and after cancer surgery, and to evaluate the usability and feasibility of the intervention. A total of 15 patients scheduled for abdominal cancer surgery consented to the study, which involved using a Fitbit smartwatch with a companion smartphone app across the perioperative period (from a minimum of 2 weeks before surgery to 30 days postdischarge). Participants received prompts to walk after any SB that exceeded a prespecified threshold, which varied from day to day based on patient-reported symptom severity. Participants also completed weekly semistructured interviews to collect information on usability, acceptability, and experience using the app and smartphone; in addition, smartwatch logs were examined to assess participant study compliance. Of eligible patients approached, 79% (15/19) agreed to participate. Attrition was low (1/15, 7%) and due to poor health and prolonged hospitalization. Participants rated (0-100) the smartphone and smartwatch apps as very easy (mean 92.3 and 93.2, respectively) and pleasant to use (mean 93.0 and 93.2, respectively). Overall satisfaction with the whole system was 89.9, and the mean System Usability Scale score was 83.8 out of 100. Overall compliance with symptom reporting was 51% (469/927 days), decreasing significantly from before surgery (264/364, 73%) to inpatient recovery (32/143, 22%) and postdischarge (173/420, 41%). Overall Fitbit compliance was 70% (653/927 days) but also declined from before surgery (330/364, 91%) to inpatient (51/143, 36%) and postdischarge (272/420, 65%). Perioperative patients with cancer were willing to use a smartwatch- and smartphone-based real-time intervention to reduce SB, and they rated the apps as very easy and pleasant to use. Compliance with the intervention declined significantly after surgery. The effects of the intervention on postoperative activity patterns, recovery, and quality of life will be evaluated in an ongoing randomized trial.


Sustaining corporate class consciousness across the new liquid managerial elite in Britain.
This article asks: how is class consciousness and cohesiveness amongst the UK business elite maintained in the twenty-first century? Elite studies traditionally sought to account for the construction and circulation of dominant ideology through exclusive education systems, institutional board interlocks and club memberships. The problem is that business elite membership of all these institutions has been steady declining in recent decades. Contemporary corporate elites now appear more mobile and fragmented in an age of globalization. However, class cohesion amongst business leaders appears as strong as ever after decades of neoliberal policy hegemony. So, how are such ideas, norms and values circulated and maintained? This study tried to answer this question drawing on a set of 30 semi-structured interviews with top UK CEOs and a demographic audit of current FTSE 100 CEOs. The findings suggest that three additional means of achieving business elite coherence have become more significant: professional business education, semi-formal but regular meeting sites, and specialist business media.


Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease.
The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, motor neurons, and muscle fibers. Direct stimulation of sympathetic neurons led to activation of muscle postsynaptic β2-adrenoreceptor (ADRB2), cAMP production, and import of the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PPARGC1A) into myonuclei. Electrophysiological and morphological deficits of neuromuscular junctions upon sympathectomy and in myasthenic mice were rescued by sympathicomimetic treatment. In conclusion, this study identifies the neuromuscular junction as a target of the sympathetic nervous system and shows that sympathetic input is crucial for synapse maintenance and function.


Insights into NK cell biology from human genetics and disease associations.
Rare human primary immunodeficiency disorders with extreme susceptibility to infections in infancy have provided important insights into immune function. Increasingly, however, primary immunodeficiencies are also recognized as a cause of other more common, often discrete, infectious susceptibilities. In a wider context, loss-of-function mutations in immune genes may also cause disorders of immune regulation and predispose to cancer. Here, we review the associations between human diseases and mutations in genetic elements affecting natural killer (NK) cell development and function. Although many such genetic aberrations significantly reduce NK cell numbers or severely impair NK cell responses, inferences regarding the role of NK cells in disease are confounded by the fact that most mutations also affect the development or function of other cell types. Still, data suggest an important role for NK cells in diseases ranging from classical immunodeficiency syndromes with susceptibility to viruses and other intracellular pathogens to cancer, autoimmunity, and hypersensitivity reactions.


Comparison of peanut meal and soybean meal as protein supplements for laying hens.
Peanut protein is severely limiting in threonine and has been used to create threonine deficiency in animals. The availability of purified threonine at low cost raises the possibility of economically using peanut meal (PNM) and threonine combinations in poultry diets. An experiment was conducted to compare corn and PNM based diets to corn and soybean meal (SBM) based diets at three protein levels (16, 18.5, and 21%) in diets for 22-to-34-wk-old commercial Leghorns. Birds were housed two per cage with four cages per replicate and six replicates per treatment. Feed consumption, egg production, and feed per dozen eggs were almost identical for PNM (93.8 g/hen per d, 92.2 eggs per 100 hens/d, and 1.22 kg/dozen) and SBM (93.7 g/hen per d, 92.2 eggs per 100 hens/d, and 1.22 kg/dozen). Dietary protein level had no consistent effect on any of these parameters but did significantly improve body weight gains and egg weights (1.2 to 2.5 g/egg). PNM-fed hens laid slightly smaller eggs during the first 6 wk (P<0.05), but there were no egg size differences during the last 6 wk of the experiment (P>0.14). PNM-fed hens laid eggs with better interior quality at 26 and 30 wk of age. After 2 wk of storage, Haugh units remained better for eggs from hens fed PNM than SBM when kept refrigerated (4 degrees C; P<0.05) or at room temperature (20 degrees C; P<0.10). Egg specific gravity was slightly lower for hens fed PNM. It is concluded that PNM is an excellent ingredient for laying hen diets.


Effect of intravenous contrast material on the integrity of the blood-brain barrier: experimental study.
Increasingly large doses of contrast medium have been advocated for enhanced computed tomography. It is assumed that such large intravenous doses, which increase the osmolality of the blood, do not affect the blood-brain barrier in the same way as intracarotid injections of the same solutions. Using a qualitative marker, Evans blue dye, and a quantitative marker, 99mTc-pertechnetate, a study was performed in rabbits to assess the effect of intravenous sodium iothalamate (Conray-420) at a dose of 8 ml/kg on the integrity of the blood-brain barrier. No qualitative or quantitative evidence of disruption of the blood-brain barrier was demonstrated. Since histologic examination was not done, morphologic changes cannot be excluded.


Rehabilitation modality and onset differentially influence whisker sensory hypersensitivity after diffuse traumatic brain injury in the rat.
As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI.


Death by necrosis. Uncontrollable catastrophe, or is there order behind the chaos?
Cells suffer necrotic death when exposed to extreme environmental conditions, adverse and excessive stimuli, or when deleterious mutations are encoded in their genetic material. Unlike apoptosis, which involves a highly regulated and elaborate network of biochemical events and cascades, necrosis has been considered generally to be a chaotic decadence process that effects the inexorable demise of cells otherwise not destined to die. This grim prospect is now slowly being overturned, mostly by exciting new findings in two simple model organisms, Caenorhabditis elegans and Drosophila melanogaster. Despite the wide spectrum of necrosis-initiating conditions, evidence is accumulating that execution of necrotic or neurodegenerative cell death may be carried out by a finite common set of mechanisms.


[Neuropathology of progressive multifocal leukoencephalopathy].
Progressive multifocal leukoencephalopathy (PML) is caused by opportunistic infection of JC virus which belongs to Papovavirus, and presents with progressive demyelinating lesion in the central nervous system. PML was originally reported as a rare complication of hematologic disorders, but later greatly increased in number in association with acquired immunodeficeincy syndrome (AIDS). Original neuropathological features of PML consist of demyelination lacking inflammatory reaction or necrosis, accompanying oligodendroglial nuclear inclusions in the periphery of demyelination. The lesion is preferentially localized to gray-white junction of the cerebral hemisphere and manifests as characteristic demyelinating lesion, called scallopping. Detection of JC virus is essential for the final diagnosis of PML and is achieved via immunohistochemical detection of JC virus with antibodies raised against their components, ultrastructural demonstration of virions characteristic of JC virus, or detection with in-situ hybridization of the genome of JC virus. JC virus can replicate only in oligodendroglial cells, but astrocytes are frequently infected by the virus. The resume of immunological function through therapeutic intervention develops new pathology in PML, exhibiting severe inflammatory reaction with edema and necrosis. This new pathological feature is called immune reconstruction syndrome and clinically presents with severe progression in symptoms of the central nervous system. Nevertheless, treatment of PML is directed for the elimination of the viruses by host immune system. The modification of the above immune reconstruction syndrome is essential for successful outcome of such therapeutic trial.


Insect resistance of transgenic tobacco plants expressing delta-endotoxin gene of Bacillus thuringiensis.
The initiative B.thuringiensis delta-endotoxin (Bt toxin) gene clones TH12 and TH48 contain two different classes of homologous genes, the 5.3 kb class and 6.6 kb class, respectively. Bt toxin genes of both classes, modified at the 5'-end and truncated at the 3'-end, can still be expressed to produce the insecticidal, truncated toxin proteins in E. coli. The modified Bt toxin genes were inserted into the plant binary expression vector pBin 437 (a derivative plasmid of pBin 19) and were transferred into tobacco by Ti plasmid-mediated gene transfer system. Southern blot and DNA slot blot analysis indicate that the Bt toxin genes have been integrated into tobacco genome at a copy number of 1 to 5. Northern blot analysis of polyA+ RNAs from progeny of the transgenic plants revealed that Bt toxin genes of both 5.3 kb and 6.6 kb classes were expressed in transgenic plants, though the transcripts were degraded to RNAs of lower molecular weights. In insecticidal test, 5 plants from the progeny of 5.3 kb class gene-transformed SR1 tobacco plants and 3 plants from those of 6.6 kb class gene-transformed plants were found to be toxic to the testing larvea of H.assulta. In comparison with the control, mortality of the insects fed on transgenic plants reached 40-50% and the growth of the survived insects was remarkably inhibited. These results indicate that the modified Bt genes of the 5.3 kb and 6.6 kb classes were expressed in transgenic plants and could confer on the transgenic plants a new character of insect resistance.


Sustained Reduction in Bloodstream Infections in Infants at a Large Tertiary Care Neonatal Intensive Care Unit.
Bloodstream infections (BSI) cause significant morbidity and mortality among hospitalized infants. Reduction of BSIs has emerged as an important patient safety goal. Implementation of central line insertion bundles, standardized line care protocols, and health care provider education programs have reduced BSI in NICUs around the country. The ability of large tertiary care centers to decrease nosocomial infections, including BSI, has been demonstrated. However, long-term BSI reductions in infants are not well documented. We sought to demonstrate that a low incidence of BSI can be maintained over time in a tertiary care NICU. Baseline BSI incidence for infants admitted to the NICU was 5.15 and 6.08 episodes per 1000 infant-days in 2005 and 2006, respectively. After protocol implementation, the incidence of BSI decreased to 2.14/1000 infant-days and 2.44/1000 infant-days in 2008 and 2009, respectively. Yearly incidence remained low over the next 4 years and decreased even further to 0.20 to 0.45 infections per 1000 infant-days. This represents a 92% decrease in BSI over a period of more than 5 years. Implementation of a nursing-led comprehensive infection control initiative can effectively produce and maintain a reduction in the incidence of BSI in infants at a large tertiary care NICU. Additional research is needed to effectively expand prevention of central line-associated BSIs to BSIs of all etiologies.


Stenosis in antiphospholipid syndrome: a new finding with clinical implications.
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a variety of clinical manifestations. Recent studies suggest arterial stenosis is involved in APS. Furthermore, arterial stenosis may be a relevant and treatable cause for hypertension, renal, CNS and gastrointestinal manifestations of APS. Our objective was to overview the published data regarding arterial stenosis in APS--the clinical presentation, diagnosis, suggested therapies and the possible mechanisms. We searched PUBMED (1951-2006) reference lists for the role of arterial stenosis in APS. APS patients might present with arterial stenosis. Its recognition has important diagnostic and therapeutic implications. Articles suggest that anticoagulation treatment with INR above three may reverse the artery stenosis and achieve subsequent clinical improvement. Currently, there are no specific guidelines for the management of APS patients with arterial stenosis. The exact mechanism of arterial stenosis in APS patients remains unclear.


Disturbance of circadian gene expression in hepatocellular carcinoma.
Circadian rhythm plays an important role in the regulation of digestive system. The human circadian rhythm is controlled by at least nine circadian genes. The aims of this study are to understand the expression of the circadian genes between hepatocellular carcinoma tissues and nontumor tissues, and to explore the possible mechanism(s) contributing to the difference. We analyzed differential expression of the 9 circadian genes in 46 hepatocellular carcinoma and paired noncancerous tissues by real-time quantitative RT-PCR and immunohistochemical detection. We also tested the possible regulatory mechanism(s) by direct sequencing and methylation PCR analysis. Our results showed that decreased expression levels of PER1, PER2, PER3, CRY2, and TIM in hepatocellular carcinomas were observed. Decreased-expression of these genes was not caused by genetic mutations, but by several factors, such as promoter methylation, overexpression of EZH2 or other factors. The down expression of more circadian genes may result in disturbance of cell cycle, and it is correlated with the tumor size. Downregulation of circadian genes results in disturbance of circadian rhythm in hepatocellular carcinoma which may disrupt the control of the central pacemaker and benefit selective survival of cancerous cells and promote carcinogenesis.


Successful restoration of a tropical shallow eutrophic lake: Strong bottom-up but weak top-down effects recorded.
Fish manipulation has been used to restore lakes in the temperate zone. Often strong short-term cascading effects have been obtained, but the long term-perspectives are less clear. Fish manipulation methods are far less advanced for warm lakes, and it is debatable whether it is, in fact, possible to create a trophic cascade in warm lakes due to the dominance and high densities of fast-reproducing omnivorous fish. However, removal of benthic feeding fish also reduce disturbance of the sediment, which not only affects the nutrient level but also the concentration of suspended organic and inorganic matter with enhanced water clarity and potentially better growth conditions for submerged macrophytes. We conducted a biomanipulation experiment in one of the basins in Chinese Huizhou West Lake that have remained highly turbid after extensive nutrient loading reduction. Another basin was used as control (control-treatment pairing design). Removal of a substantial amount of plankti-benthivorous fish was followed by planting of submerged macrophytes and stocking of piscivorous fish. We found strong and relatively long-lasting effects of the restoration initiative in the form of substantial improvements in water clarity and major reductions in nutrient concentrations, particularly total phosphorus, phytoplankton and turbidity, while only minor effects were detected for crustacean zooplankton grazers occurring in low densities before as well as after the restoration. Our results add importantly to the existing knowledge of restoration of warm lakes and are strongly relevant, not least in Asia where natural lakes frequently are used extensively for fish production, often involving massive stocking of benthivorous fish. With a growing economy and development of more efficient fish production systems, the interest in restoring lakes is increasing world-wide. We found convincing evidence that fish removal and piscivores stocking combined with transplantation of submerged macrophytes may have significant effects on water clarity in warm shallow lakes even if the zooplankton grazing potential remains low, the latter most likely as a result of high predation on the zooplankton.


Induction of endotoxin tolerance by pathogenic Neisseria is correlated with the inflammatory potential of lipooligosaccharides and regulated by microRNA-146a.
In this article, we report that retreatment of human monocytic THP-1 cells and primary monocytes with pathogenic Neisseria or with purified lipooligosaccharides (LOS) after previous exposure to LOS induced immune tolerance, as evidenced by reduced TNF-α and IL-1β cytokine expression. LOS that we have previously shown to vary in their potential to activate TLR4 signaling, which was correlated with differences in levels of lipid A phosphorylation, had similarly variable ability to induce tolerance. Efficacy for induction of tolerance was proportional to the level of lipid A phosphorylation, as LOS from meningococcal strain 89I with the highest degree of phosphorylation was the most tolerogenic following retreatment with LOS or whole bacteria, compared with LOS from gonococcal strains 1291 and GC56 with reduced levels of phosphorylation. Hydrogen fluoride treatment of 89I LOS to remove phosphates rendered the LOS nontolerogenic. Tolerance induced by the more highly inflammatory meningococcal LOS was correlated with significantly greater downregulation of p38 activation, greater induction of the expression of A20 and of microRNA-146a, and greater reductions in IL-1R-associated kinase 1 and TRAF6 levels following LOS retreatment of cells. The role of miR-146a in regulation of induction of TNF-α was confirmed by transfecting cells with an inhibitor and a mimic of miR-146a. Our results provide a mechanistic framework for understanding the variable pathophysiology of meningococcal and gonococcal infections given that after an initial exposure, greater upregulation of microRNA-146a by more highly inflammatory LOS conversely leads to the suppression of immune responses, which would be expected to facilitate bacterial survival and dissemination.


A theory of working memory without consciousness or sustained activity.
Working memory and conscious perception are thought to share similar brain mechanisms, yet recent reports of non-conscious working memory challenge this view. Combining visual masking with magnetoencephalography, we investigate the reality of non-conscious working memory and dissect its neural mechanisms. In a spatial delayed-response task, participants reported the location of a subjectively unseen target above chance-level after several seconds. Conscious perception and conscious working memory were characterized by similar signatures: a sustained desynchronization in the alpha/beta band over frontal cortex, and a decodable representation of target location in posterior sensors. During non-conscious working memory, such activity vanished. Our findings contradict models that identify working memory with sustained neural firing, but are compatible with recent proposals of 'activity-silent' working memory. We present a theoretical framework and simulations showing how slowly decaying synaptic changes allow cell assemblies to go dormant during the delay, yet be retrieved above chance-level after several seconds.


No difference in return to play rates between different elite sports after primary autograft ACL reconstruction.
To demonstrate return to play (RTP) rates, the level of RTP and time taken to RTP in different sports after anterior cruciate ligament reconstruction (ACL-R) and compare the differences between football and rugby. The secondary aims were to compare the differences in intra articular injuries and their treatments and reoperation rates between these sports. A retrospective review of a consecutive series of all primary ACL-R undertaken by the senior author between 2005 and 2019 was undertaken. Patients were included if they were elite athletes and were a minimum of 2 year post-primary autograft ACL-R. The outcomes measured were RTP (defined as participation in a professional match or in national/international-level competition in amateur sports), time to RTP after surgery and RTP level (Tegner score). Three hundred and ninety-four elite athletes, with 420 ACL-Rs were included. 235 (55.9%) were in footballers and 125 (29.8%) were in rugby players. 399 (95.0%) of all elite athletes returned to competition at an average of 10.3 months after ACL-R. 386 (90.2% played at the same or higher level post-surgery. Although there was no difference in RTP rates between different sports, rugby players RTP significantly faster than footballers (9.6 vs 10.6 months, (p = 0.027). Footballers were more likely to rupture their ACL during jumping/landing manoeuvres and to receive a PT graft than rugby players. There were no other significant differences between football and rugby players regarding patient characteristics, intraoperative findings, re-rupture and re-operation rates. Over 95% of all elite athletes RTP after primary ACL-R with 90% able to play at the same level. Rugby players RTP significantly faster than footballers. Level IV.


[Comparative evaluation of 2 plans of study for the career of surgeon: a theoretical-conceptual approach].
The authors describe a specific experiment concerning the degree of medical doctor and surgeon in the Zaragoza National School of Professional Studies of the National Autonomous University of Mexico (UNEP-Zaragoza). The experiment was prompted by the concurrence at a certain point of two study programs: the traditional one, which had been in use for a number of years, and a recently introduced modular program. The analysis reported in this paper was made by the prospective self-evaluation method devised in PAHO's Manpower Development Program in 1986. Results indicated that the modular program brings medical education closer to the ideal standard of the physician that Mexico's health services need, more consistently and conclusively than the traditional subject-oriented program. The modular program was rated more highly in 65.9% of the 41 indicators used. UNEP-Zaragoza is conducting two more research projects to validate the forecasts produced by the self-evaluation method. The results will be published in coming issues of this quarterly.


Bradykinesia akinesia inco-ordination test (BRAIN TEST): an objective computerised assessment of upper limb motor function.
A simple and rapid computerised keyboard test, based on the alternating finger tapping test, has been developed to quantify upper limb motor function. The test generates several variables: (1) kinesia score: the number of keystrokes in 60 seconds; (2) akinesia time: cumulative time that keys are depressed; (3) dysmetria score: a weighted index calculated using the number of incorrectly hit keys corrected for speed; (4) incoordination score: a measure of rhythmicity which corresponds to the variance of the time interval between keystrokes. The BRAIN TEST(Copyright ) was assessed on 35 patients with idiopathic Parkinson's disease, 12 patients with cerebellar dysfunction, and 27 normal control subjects. The mean kinesia scores of patients with Parkinson's disease or cerebellar dysfunction were significantly slower than normal controls (Parkinson's disease=107 (SD 28) keys/min v cerebellar dysfunction=86+/- (SD 28) v normal controls=182 (SD 26), p<0.001) and correlated with the UPDRS (r =-0.69, p<0.001). The akinesia time is very insensitive and was only abnormal in patients with severe parkinsonism. The median dysmetria (cerebellar dysfunction=13.8 v Parkinson's disease=6.1 v normal controls=4.2, p=0.002) and inco-ordination scores (cerebellar dysfunction=5.12 v Parkinson's disease=0.84 v normal controls=0.15, p=0.002) were significantly higher in patients with cerebellar dysfunction, in whom the dysmetria score correlated with a cerebellar disease rating scale (r=0.64, p=0.02). The BRAIN TEST(Copyright ) provides a simple, rapid, and objective assessment of upper limb motor function. It assesses speed, accuracy, and rhythmicity of upper limb movements regardless of their physiological basis. The results of the test correlate well with clinical rating scales in Parkinson's disease and cerebellar dysfunction. The BRAIN test will be useful in clinical studies. It can be downloaded from the Internet ().


High-grade endometrial stromal sarcoma displaying immunohistochemical expression of BCOR-A report of two cases of a novel tumor entity.
Several defining molecular alterations have recently been identified underlying high-grade endometrial stromal sarcomas, such as YWHAE: NUTM2A/B fusions, ZC3H7B: BCOR fusions, and BCOR internal tandem duplication (ITD). BCOR is a useful immunohistochemical marker for identifying these tumors. A 37-year-old lady was presented with a 10-cm-sized tumor in the pouch of Douglas, involving the vaginal vault, bilateral adnexa, and peritoneum. A 53-year-old lady with a prior hysterectomy was presented with a 12-cm-sized tumor in the vault with abdominal deposits. Histopathological examination of both tumors revealed atypical cells comprising oval to spindle-shaped nuclei, a variable amount of myxoid stroma, and mitotic figures exceeding 10/10 high power fields. Immunohistochemically, the former tumor was diffusely positive for CD10, and the second tumor displayed patchy staining. Both tumors were positive for BCOR. Estrogen receptor (ER) showed variable staining in both tumors. By fluorescence in-situ hybridization (FISH), both tumors lacked YWHAE gene rearrangement. Both tumors had an aggressive clinical course, including extensive involvement This constitutes the first report of BCOR-positive high-grade sarcomas involving the female genital tract from our subcontinent. BCOR is a useful immunostain for identifying these relatively aggressive tumors. The differential diagnoses and the prognosis of these ultra-rare tumors are discussed herewith.


Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model.
Overexpression studies have shown that the small heat shock proteins (sHSP) protect the myocardium from ischemia-reperfusion (I/R)-induced damage. However, gene deletion studies are necessary to demonstrate whether sHSPs are required for protection. The genes for alphaB-crystallin (alphaBC) and HSPB2, two sHSPs that are expressed in high levels in the heart, are in close proximity to one another; as a result, both genes were disrupted in a recently generated knockout (KO) mouse line. The alphaBC/HSPB2 KO mouse line is currently the only model that features disruption of sHSPs normally expressed in the heart. Accordingly, we examined the cardiac morphology, function, and response to I/R-induced stress in alphaBC-HSPB2 KO mice. Initial gross, light microscopic and echocardiographic characterization showed that the morphological and functional properties of hearts from adult KO mice were indistinguishable from age-matched wild-type (WT) mice. Electron microscopy showed that, compared with WT mouse hearts, KO mouse heart sarcomeres were relatively normal. Isolated perfused KO mouse hearts displayed normal contractility; however, when compared with WT, after I/R, KO mouse hearts exhibited a twofold reduction in contractile recovery, as well as increased necrosis and apoptosis. Additionally, when compared with WT, KO mouse hearts exhibited 43% less reduced glutathione, which is known to protect from I/R-induced damage. Thus, whereas neither alphaBC nor HSPB2 is essential for myocardial development and function under nonstressful conditions, one or both are required for maximal functional recovery and protection from I/R-induced necrosis and apoptosis.


Improving Quality of Care in Primary Health-Care Facilities in Rural Nigeria: Successes and Challenges.
Nigeria has a high population density but a weak health-care system. To improve the quality of care, 3 organizations carried out a quality improvement pilot intervention at the primary health-care level in selected rural areas. To assess the change in quality of care in primary health-care facilities in rural Nigeria following the provision of technical governance support and to document the successes and challenges encountered. A total of 6 states were selected across the 6 geopolitical zones of the country. However, assessments were carried out in 40 facilities in only 5 states. Selection was based on location, coverage, and minimum services offered. The facilities were divided randomly into 2 groups. The treatment group received quality-of-care assessment, continuous feedback, and improvement support, whereas the control group received quality assessment and no other support. Data were collected using the SafeCare Healthcare Standards and managed on the SafeCare Data Management System-AfriDB. Eight core areas were assessed at baseline and end line, and compliance to quality health-care standards was compared. Outcomes from 40 facilities were accepted and analyzed. Overall scores increased in the treatment facilities compared to the control facilities, with strong evidence of improvement (t = 5.28, P = .0004) and 11% average improvement, but no clear pattern of improvement emerged in the control group. The study demonstrated governance support and active community involvement offered potential for quality improvement in primary health-care facilities.


CLIF, a novel cycle-like factor, regulates the circadian oscillation of plasminogen activator inhibitor-1 gene expression.
The onset of myocardial infarction occurs frequently in the early morning, and it may partly result from circadian variation of fibrinolytic activity. Plasminogen activator inhibitor-1 activity shows a circadian oscillation and may account for the morning onset of myocardial infarction. However, the molecular mechanisms regulating this circadian oscillation remain unknown. Recent evidence indicates that basic helix-loop-helix (bHLH)/PAS domain transcription factors play a crucial role in controlling the biological clock that controls circadian rhythm. We isolated a novel bHLH/PAS protein, cycle-like factor (CLIF) from human umbilical vein endothelial cells. CLIF shares high homology with Drosophila CYCLE, one of the essential transcriptional regulators of circadian rhythm. CLIF is expressed in endothelial cells and neurons in the brain, including the suprachiasmatic nucleus, the center of the circadian clock. In endothelial cells, CLIF forms a heterodimer with CLOCK and up-regulates the PAI-1 gene through E-box sites. Furthermore, Period2 and Cryptochrome1, whose expression show a circadian oscillation in peripheral tissues, inhibit the PAI-1 promoter activation by the CLOCK:CLIF heterodimer. These results suggest that CLIF regulates the circadian oscillation of PAI-1 gene expression in endothelial cells. In addition, the results potentially provide a molecular basis for the morning onset of myocardial infarction.


Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in Parkinson's disease and its model: neurotrophic implication in nigrostriatal neurons.
Epidermal growth factor (EGF) is a member of a structurally related family containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that exerts neurotrophic activity on midbrain dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease (PD), we measured the protein content of EGF, TGFalpha, and HB-EGF in post-mortem brains of patients with Parkinson's disease and age-matched control subjects. Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal cortex and the striatum of patients. In contrast, HB-EGF and TGFalpha levels were not significantly altered in either region. The expression of EGF receptors (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the striatum of the PD model were markedly reduced on the lesioned side, compared with the control hemisphere. Subchronic supplement of EGF in the striatum of the PD model locally prevented the dopaminergic neurodegeration as measured by tyrosine hydroxylase immunoreactivity. These findings suggest that the neurotrophic activity of EGF is maintained by afferent signals of midbrain dopaminergic neurons and is impaired in patients with Parkinson's disease.


Effects of a 5-h hilly running on ankle plantar and dorsal flexor force and fatigability.
This study aimed to examine the effects of a 5-h hilly run on ankle plantar (PF) and dorsal flexor (DF) force and fatigability. It was hypothesised that DF fatigue/fatigability would be greater than PF fatigue/fatigability. Eight male trail long distance runners (42.5 ± 5.9 years) were tested for ankle PF and DF maximal voluntary isokinetic contraction strength and fatigue resistance tests (percent decrement score), maximal voluntary and electrically evoked isometric contraction strength before and after the run. Maximal EMG root mean square (RMS(max)) and mean power frequency (MPF) values of the tibialis anterior (TA), gastrocnemius lateralis (GL) and soleus (SOL) EMG activity were calculated. The peak torque of the potentiated high- and low-frequency doublets and the ratio of paired stimulation peak torques at 10 Hz over 100 Hz (Db10:100) were analysed for PF. Maximal voluntary isometric contraction strength of PF decreased from pre- to post-run (-17.0 ± 6.2%; P < 0.05), but no significant decrease was evident for DF (-7.9 ± 6.2%). Maximal voluntary isokinetic contraction strength and fatigue resistance remained unchanged for both PF and DF. RMS(max) SOL during maximal voluntary isometric contraction and RMS(max) TA during maximal voluntary isokinetic contraction were decreased (P < 0.05) after the run. For MPF, a significant decrease for TA (P < 0.05) was found and the ratio Db10:100 decreased for PF (-6.5 ± 6.0%; P < 0.05). In conclusion, significant isometric strength loss was only detected for PF after a 5-h hilly run and was partly due to low-frequency fatigue. This study contradicted the hypothesis that neuromuscular alterations due to prolonged hilly running are predominant for DF.


Carbon metabolism snapshot by ddPCR during the early step of Candida albicans phagocytosis by macrophages.
During Candida macrophage interactions, phagocytosed yeast cells feed in order to grow, develop hyphae and escape. Through numerous proteomic and transcriptomic studies, two metabolic phases have been described. A shift to a starvation mode is generally identified as early as one-hour post phagocytosis, followed by a glycolytic growth mode after C. albicans escaped from the macrophage. Healthy macrophages contain low amounts of glucose. To determine if this carbon source was sensed and metabolized by the pathogen, we explored the transcription level of a delimited set of key genes expressed in C. albicans cells during phagocytosis by macrophages, at an early stage of the interaction. This analysis was performed using a technical digital droplet PCR approach to quantify reliably the expression of carbon metabolic genes after 30 min of phagocytosis. Our data confirm the technique of digital droplet PCR for the detection of C. albicans transcripts using cells recovered after a short period of phagocytosis. At this stage, carbon metabolism is clearly oriented towards the use of alternative sources. However, the activation of high-affinity glucose transport system suggests that the low amount of glucose initially present in the macrophages is detected by the pathogen.


Ultra-fast hybrid CPU-GPU multiple scatter simulation for 3-D PET.
Scatter correction is very important in 3-D PET reconstruction due to a large scatter contribution in measurements. Currently, one of the most popular methods is the so-called single scatter simulation (SSS), which considers single Compton scattering contributions from many randomly distributed scatter points. The SSS enables a fast calculation of scattering with a relatively high accuracy; however, the accuracy of SSS is dependent on the accuracy of tail fitting to find a correct scaling factor, which is often difficult in low photon count measurements. To overcome this drawback as well as to improve accuracy of scatter estimation by incorporating multiple scattering contribution, we propose a multiple scatter simulation (MSS) based on a simplified Monte Carlo (MC) simulation that considers photon migration and interactions due to photoelectric absorption and Compton scattering. Unlike the SSS, the MSS calculates a scaling factor by comparing simulated prompt data with the measured data in the whole volume, which enables a more robust estimation of a scaling factor. Even though the proposed MSS is based on MC, a significant acceleration of the computational time is possible by using a virtual detector array with a larger pitch by exploiting that the scatter distribution varies slowly in spatial domain. Furthermore, our MSS implementation is nicely fit to a parallel implementation using graphic processor unit (GPU). In particular, we exploit a hybrid CPU-GPU technique using the open multiprocessing and the compute unified device architecture, which results in 128.3 times faster than using a single CPU. Overall, the computational time of MSS is 9.4 s for a high-resolution research tomograph (HRRT) system. The performance of the proposed MSS is validated through actual experiments using an HRRT.


Vimo - Visual Analysis of Neuronal Connectivity Motifs.
Recent advances in high-resolution connectomics provide researchers with access to accurate petascale reconstructions of neuronal circuits and brain networks for the first time. Neuroscientists are analyzing these networks to better understand information processing in the brain. In particular, scientists are interested in identifying specific small network motifs, i.e., repeating subgraphs of the larger brain network that are believed to be neuronal building blocks. Although such motifs are typically small (e.g., 2 - 6 neurons), the vast data sizes and intricate data complexity present significant challenges to the search and analysis process. To analyze these motifs, it is crucial to review instances of a motif in the brain network and then map the graph structure to detailed 3D reconstructions of the involved neurons and synapses. We present Vimo, an interactive visual approach to analyze neuronal motifs and motif chains in large brain networks. Experts can sketch network motifs intuitively in a visual interface and specify structural properties of the involved neurons and synapses to query large connectomics datasets. Motif instances (MIs) can be explored in high-resolution 3D renderings. To simplify the analysis of MIs, we designed a continuous focus&context metaphor inspired by visual abstractions. This allows users to transition from a highly-detailed rendering of the anatomical structure to views that emphasize the underlying motif structure and synaptic connectivity. Furthermore, Vimo supports the identification of motif chains where a motif is used repeatedly (e.g., 2 - 4 times) to form a larger network structure. We evaluate Vimo in a user study and an in-depth case study with seven domain experts on motifs in a large connectome of the fruit fly, including more than 21,000 neurons and 20 million synapses. We find that Vimo enables hypothesis generation and confirmation through fast analysis iterations and connectivity highlighting.


As, Hg, and Se flue gas sampling in a coal-fired power plant and their fate during coal combustion.
As, Hg, and Se are the most volatile elements in the flue gas from a coal-fired power plant. Significant amounts of these elements cause an undesired direct gaseous emission, which leads to a serious environmental health risk. The main focus of this study is to evaluate the possibility of simultaneous sampling of these volatile elements using an accurate official method for Hg (the most volatile element). A study of As, Hg, and Se emissions from a 1400 MW coal-fired power plant equipped with electrostatic precipitators (ESPs) was carried out for the combustion of a mixture of two types of coal. Simultaneous sampling of coal, bottom ash, fly ash, flue gas, and particles associated with the gas phase has been performed. Flue gas has been sampled by the Ontario Hydro Method Sampling Train, an ASTM method for Hg speciation. This sampling method was tested for As and Se sampling. As and Se determinations have been performed by HG-AAS, and Hg has been determined by CV-AAS. The results were used to examine the following: overall mass balances, relative distribution of these elements in the coal-fired power plant; As, Hg, and Se concentrations in coal and combustion residues; and predominant oxidation state for Hg in flue gas. The mass balances obtained for As, Hg, and Se were satisfactory in all cases; nevertheless, relative enrichment values in fly ash for As and Se were low; therefore, we concluded that As sampling in flue gas can be conducted by application of the Ontario Hydro Method; nevertheless Se released in the gas phase is not completely collected by this sampling train. Application of this sampling method allowed for performance of Hg speciation. The results indicated that Hg(II) was the predominant species in flue gas. It has also been proved that 24%, more than 99.8%, and 90% for As, Hg, and Se in the stack emissions, respectively, were in the gaseous phase.


TAR syndrome and esophagial atresia: a concomitant or variant condition?
Thrombocytopenia with absent radii (TAR) is rare cause of neonatal thrombocytopenia. TAR syndrome and esophageal atresia with tracheoesophageal fistula has been reported in only two cases in literature. Our case was the first in literature with unilateral TAR syndrome and bilateral absence of thumbs accompanying EA.


Wafer-scale Fabrication of Non-Polar Mesoporous GaN Distributed Bragg Reflectors via Electrochemical Porosification.
Distributed Bragg reflectors (DBRs) are essential components for the development of optoelectronic devices. For many device applications, it is highly desirable to achieve not only high reflectivity and low absorption, but also good conductivity to allow effective electrical injection of charges. Here, we demonstrate the wafer-scale fabrication of highly reflective and conductive non-polar gallium nitride (GaN) DBRs, consisting of perfectly lattice-matched non-polar (11-20) GaN and mesoporous GaN layers that are obtained by a facile one-step electrochemical etching method without any extra processing steps. The GaN/mesoporous GaN DBRs exhibit high peak reflectivities (>96%) across the entire visible spectrum and wide spectral stop-band widths (full-width at half-maximum >80 nm), while preserving the material quality and showing good electrical conductivity. Such mesoporous GaN DBRs thus provide a promising and scalable platform for high performance GaN-based optoelectronic, photonic, and quantum photonic devices.


Toward an optimal distribution of b values for intravoxel incoherent motion imaging.
The intravoxel incoherent motion (IVIM) theory provides a framework for the separation of perfusion and diffusion effects in diffusion-weighted imaging (DWI). To measure the three free IVIM parameters, DWIs with several diffusion weightings b must be acquired. To date, the used b value distributions are chosen heuristically and vary greatly among researchers. In this work, optimal b value distributions for the three parameter fit are determined using Monte-Carlo simulations for the measurement of a low, medium and high IVIM perfusion regime. The first 16 b values of a b value distribution, which was optimized to be appropriate for all three regimes, are {0, 40, 1000, 240, 10, 750, 90, 390, 170, 10, 620, 210, 100, 0, 530 and 970} in units of seconds per square meter. This distribution performed well for all organs and outperformed a distribution frequently used in the literature. In case of limited acquisition time, the b values should be chosen in the given order, but at least 10 b values should be used for current clinical settings. The overall parameter estimation quality depends strongly and nonlinearly on the signal-to-noise ratio (SNR): it is essential that the SNR is considerably higher than a critical SNR. This critical SNR is about 8 for medium and high IVIM perfusion and 50 for the low IVIM perfusion regime. Initial in vivo IVIM measurements were performed in the abdomen and were in keeping with the numerically simulated results.


Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients.
Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia. Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10-20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days). Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 μg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 μg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies. Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.


An interactive web-based Pseudomonas aeruginosa genome database: discovery of new genes, pathways and structures.
Using the complete genome sequence of Pseudomonas: aeruginosa PAO1, sequenced by the Pseudomonas: Genome Project (ftp://ftp.pseudomonas. com/data/pacontigs.121599), a genome database (http://pseudomonas. bit.uq.edu.au/) has been developed containing information on more than 95% of all ORFs in Pseudomonas: aeruginosa. The database is searchable by a variety of means, including gene name, position, keyword, sequence similarity and Pfam domain. Automated and manual annotation, nucleotide and peptide sequences, Pfam and SMART domains (where available), Medline and GenBank links and a scrollable, graphical representation of the surrounding genomic landscape are available for each ORF. Using the database has revealed, among other things, that P. aeruginosa contains four chemotaxis systems, two novel general secretion pathways, at least three loci encoding F17-like thin fimbriae, six novel filamentous haemagglutinin-like genes, a number of unusual composite genetic loci related to vgr/RHS: elements in Escherichia coli, a number of fix-like genes encoding a micro-oxic respiration system, novel biosynthetic pathways and 38 genes containing domains of unknown function (DUF1/DUF2). It is anticipated that this database will be a useful bioinformatic tool for the Pseudomonas: community that will continue to evolve.


Trophoblast alterations in the placental bed in relation to physiological changes in spiral arteries.
Ninety-three placental bed biopsies containing a segment of a spiral artery at the level of the decidual-myometrial junction (53 with and 40 without physiological changes) were histologically investigated for depth of trophoblastic penetration of the uterine wall, formation of trophoblastic multinucleated giant cells and the enzyme histochemical characteristics of the interstitial (stromal) and vascular (intramural) trophoblast. The depth of trophoblastic penetration was not related to the presence or absence of the physiological changes. Conversely, in the absence of physiological changes, a significant accumulation of multinucleated giant cells at the decidual-myometrial junction was found before 36 weeks of gestation. The enzyme histochemical characteristics of the placental bed trophoblast suggest a stromal migration of trophoblast to the proximal (decidual-myometrial) part of the spiral artery whereas the distal part might be invaded by intraluminal (upstream) invasion. The hypothesis is put forward that in the absence of physiological changes a disturbed stromal migration is caused by intrinsic (trophoblastic) or extrinsic (interstitial of vascular) factors expressed by the augmentation of the multinucleated cells at the decidual-myometrial junction.


A comparison between the patella and the calcaneus using ultrasound velocity and attenuation as predictors of bone mineral density.
The bone mineral density (BMD), ultrasound velocity (UV) and attenuation were examined in sixteen matched sets of human patellae and calcanei. For the sixteen calcanei, BMD was strongly correlated with all ultrasound parameters. Calcaneal UV appeared to be inferior to attenuation in the ability to predict BMD. For the sixteen patellae, the average UV was found to be greater in the superior/inferior direction than in the anterior/posterior and medial/lateral directions. It was found that patella BMD was significantly correlated with each of three directional ultrasound velocities. The relationship between BMD and ultrasound attenuation parameters was not significant in the patella. A comparative study of the two different bone sets demonstrated that the BMDs of the patella and calcaneus were significantly correlated with each other. Ultrasound velocity of calcaneus, measured in the medial/lateral direction, was not significantly associated with any of three directional ultrasound velocities in the patella. Similarly, ultrasound attenuation parameters of calcaneus were not significantly correlated with those of patella. The present study also demonstrated evidence that when predicting BMDs at their respective sites using ultrasound, the calcaneus appeared to be superior to the patella.


Central nervous system injury and neurobiobehavioral function in children with brain tumors: a review of the literature.
Children with brain tumors present a complex set of factors when considering treatment decisions, including type and location of tumor and age of the child. Two-thirds of children will survive, but historically have had poorer neurocognitive and quality-of-life outcomes when compared with survivors of other childhood cancers. Delaying or forgoing cranial radiation completely is thought to lead to improved neurobiobehavioral outcomes, but there is still relatively little research in this area. The objectives of this study were to review and consolidate what is known about the effects of cranial radiation and chemotherapy on normal brain tissue and to synthesize that information relative to neurobiobehavioral findings in children with brain tumors. A literature search using PubMed and PsycINFO from 2000 to 2011 was done using a variety of terms related to childhood brain tumor treatment and outcome. A total of 70 articles were reviewed, and 40 were chosen for inclusion in the review based on most relevance to this population. Both cranial radiation and certain chemotherapy agents cause damage to or loss of healthy neurons, as well as a decrease in the number of progenitor cells of the hippocampus. However, in general, children treated with chemotherapy alone appear to have less of a neurobiobehavioral impact than those treated with cranial radiation. The trend toward delaying or postponing cranial radiation when possible may improve overall neurocognitive and quality-of-life outcomes. Nurses require knowledge of these issues when discussing treatment with families and with caring for long-term survivors.


Effects of butylated hydroxyanisole on the metabolism of benzo(a)pyrene by mouse lung microsomes.
Butylated hydroxyanisole (BHA) is a commonly used food additive with demonstrated inhibitory action against chemical carcinogenesis in animals. In order to elucidate the mechanism of the anticarcinogenic action, the effects of BHA on benzo(a)pyrene (BP) metabolism were studied with lung microsomes from female mice. BHA treatment (0.5% in the diet for 7 days) inhibited BP metabolism and altered the ratios among different metabolites as analyzed by high-performance liquid chromatography. The treatment reduced the metabolic formation of 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene, but not the production of 3-hydroxybenzo(a)pyrene and trans-4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene. Since the gross microsomal cytochrome P-450 content was not significantly affected by the treatment, the change of regioselectivity in BP metabolism was probably due to the alteration of cytochrome P-450 isozyme composition by dietary BHA. General and regioselective inhibition of BP metabolism was also observed when BHA was added to the lung microsomal incubation mixture. The formation of 9,10-dihydroxy-9,10-dihydrobenzo(a)pyrene and 9-hydroxybenzo-(a)pyrene was inhibited more severely than that of trans-4,5-dihydroxy-4,5-dihydrobenzo(a)pyrene and trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, but the production of 3-hydroxy-benzo(a)pyrene was not inhibited. Dietary BHA treatment also decreased the microsomal metabolism of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to n-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene and r-7,t-8-dihydroxy-c-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Considering that the former diol-epoxide is a suspected ultimate carcinogen, the observed inhibitions of BP metabolism in the formation of diol-epoxides may be closely related to the anticarcinogenic action of BHA.


[Concentration and distribution of glycogen in the brain following experimental cranio-cerebral injuries].
The amount and distribution of glycogen in the brain tissue in closed craniocerebral injury were studied by electron microscopy. It is shown that 24 hours after the injury the number of glycogen granules in different areas of the brain, and especially in its stem, increases sharply. The glycogen granules are found in the cytoplasm of the neurones and their processes, in the synapses, and in the cytoplasm of the glial cells. The amount of glycogen reduced when the animals were given injections of agents stimulating the central nervous system (phenamine). In contrast, inhibition of the function of the central nervous system by injection of urethane and barbital caused an increase in the glycogen content. Under such conditions, the glycogen particles were predominantly localized in the processes of the perivascular astrocytes. The change in the glycogen content is associated with the effect of the craniocerebral injury and the different functions of the central nervous system on the activity of the enzyme gamma-amylase which is concerned with the hydrolysis of glycogen and the ultimate formation of glucose, the most important energy substrate of the brain.


Modifications to Ivor Lewis esophagectomy.
The surgical approach to esophagectomy is variable. A number of factors are considered when determining the optimal approach to esophagectomy: location and extent of disease, fibrosis, additional patient factors and surgeon preference. One of the disadvantages to some approaches is the need for a change in position, which increases operative time. Also, because typically the abdomen is initially explored, patients may later be deemed unresectable at thoracotomy. We describe time saving modifications to the standard Ivor Lewis esophagectomy that eliminate the need for repositioning and facilitate a stapled end-to-end anastomosis.


HMG CoA reductase inhibitor accelerates aging effect on diaphragm mitochondrial respiratory function in rats.
We examined effects of pravastatin on age-related changes in mitochondrial function in rats. Decline in the activity of complex I of the mitochondrial electron transport chain was observed in diaphragm and psoai major in rats aged 35 and 55 weeks, and that of complex IV in rats aged 55 weeks. Pravastatin accelerated significantly age-related decline in the activity of complex I of diaphragm mitochondria, though pravastatin did not show significant effect on normally observed age-associated decline in the activities of complex IV of psoai major and diaphragm mitochondria. Aging effect on mitochondrial respiratory function was not observed on heart muscle and liver in rats up to 55 weeks old, and pravastatin did not effect significantly heart and liver mitochondrial respiratory function. From these results, careful clinical examination on respiratory muscle function should be necessary in patients treated with pravastatin particularly in elderly patients.


Bidirectional influences of anxiety and depression in young children.
Anxiety and depression tend to co-occur in children. Studies indicate that higher levels of anxiety are associated with subsequent higher levels of depression, while depression may inhibit subsequent anxiety. It is important to increase our understanding of the temporal sequencing of these disorders and, particularly, to determine if suppression effects account for the inhibitory association. In addition, further information about these relationships in young children is needed. Participants were a diverse (20.4 % Hispanic, 16.7 % African American; 49.1 % boys) community sample of 796 children with data available at ages 4, 5, and 6-7 years. Anxiety and depression symptoms were assessed using the Child Symptom Inventory and symptom count measures from the Diagnostic Interview Schedule for Children-Parent Scale -Young Child version. The results indicated: (a) anxiety and depression were relatively stable over time; (b) anxiety at age 4 and 5 was a significant positive predictor of subsequent depression; (c) while an inhibitory effect of depression on subsequent anxiety was found, that inhibitory effect was due to negative suppression, and higher levels of depression were actually associated with subsequent anxiety; (e) consistent with a significant suppression effect, when depression was included as a predictor, the association between anxiety at ages 4 and 5 and anxiety one year later increases in magnitude. Both anxiety and depression are associated with higher levels of one another in the subsequent year. Implications for prevention are discussed.


Neuromuscular function in healthy occlusion.
This study aimed to measure neuromuscular function for the masticatory muscles under a range of occlusal conditions in healthy, dentate adults. Forty-one subjects conducted maximum voluntary clenches under nine different occlusal loading conditions encompassing bilateral posterior teeth contacts with the mandible in different positions, anterior teeth contacts and unilateral posterior teeth contacts. Surface electromyography was recorded bilaterally from the anterior temporalis, superficial masseter, sternocleidomastoid, anterior digastric and trapezius muscles. Clench condition had a significant effect on muscle function (P = 0.0000) with the maximum function obtained for occlusions with bilateral posterior contacts and the mandible in a stable centric position. The remaining contact points and moving the mandible to a protruded position, whilst keeping posterior contacts, resulted in significantly lower muscle activities. Clench condition also had a significant effect on the per cent overlap, anterior-posterior and torque coefficients (P = 0.0000-0.0024), which describe the degree of symmetry in these muscle activities. Bilateral posterior contact conditions had significantly greater symmetry in muscle activities than anterior contact conditions. Activity in the sternocleidomastoid, anterior digastric and trapezius was consistently low for all clench conditions, i.e. <20% of the maximum voluntary contraction level. In conclusion, during maximum voluntary clenches in a healthy population, maximum masticatory muscle activity requires bilateral posterior contacts and the mandible to be in a stable centric position, whilst with anterior teeth contacts, both the muscle activity and the degree of symmetry in muscle activity are significantly reduced.