Physician-Pharmacist collaboration in a pay for performance healthcare environment.
Healthcare is becoming more complex and costly in both European (Slovak) and American models. Healthcare in the United States (U.S.) is undergoing a particularly dramatic change. Physician and hospital reimbursement are becoming less procedure focused and increasingly outcome focused. Efforts at Mercy Hospital have shown promise in terms of collaborative team based care improving performance on glucose control outcome metrics, linked to reimbursement. Our performance on the Centers for Medicare and Medicaid Services (CMS) post-operative glucose control metric for cardiac surgery patients increased from a 63.6% pass rate to a 95.1% pass rate after implementing interventions involving physician-pharmacist team based care.Having a multidisciplinary team that is able to adapt quickly to changing expectations in the healthcare environment has aided our institution. As healthcare becomes increasingly saturated with technology, data and quality metrics, collaborative efforts resulting in increased quality and physician efficiency are desirable. Multidisciplinary collaboration (including physician-pharmacist collaboration) appears to be a viable route to improved performance in an outcome based healthcare system (Fig. 2, Ref. 12).


Traffic Sign Detection System for Locating Road Intersections and Roundabouts: The Chilean Case.
This paper presents a traffic sign detection method for signs close to road intersections and roundabouts, such as stop and yield (give way) signs. The proposed method relies on statistical templates built using color information for both segmentation and classification. The segmentation method uses the RGB-normalized (ErEgEb) color space for ROIs (Regions of Interest) generation based on a chromaticity filter, where templates at 10 scales are applied to the entire image. Templates consider the mean and standard deviation of normalized color of the traffic signs to build thresholding intervals where the expected color should lie for a given sign. The classification stage employs the information of the statistical templates over YCbCr and ErEgEb color spaces, for which the background has been previously removed by using a probability function that models the probability that the pixel corresponds to a sign given its chromaticity values. This work includes an analysis of the detection rate as a function of the distance between the vehicle and the sign. Such information is useful to validate the robustness of the approach and is often not included in the existing literature. The detection rates, as a function of distance, are compared to those of the well-known Viola-Jones method. The results show that for distances less than 48 m, the proposed method achieves a detection rate of 87.5 % and 95.4 % for yield and stop signs, respectively. For distances less than 30 m, the detection rate is 100 % for both signs. The Viola-Jones approach has detection rates below 20 % for distances between 30 and 48 m, and barely improves in the 20-30 m range with detection rates of up to 60 % . Thus, the proposed method provides a robust alternative for intersection detection that relies on statistical color-based templates instead of shape information. The experiments employed videos of traffic signs taken in several streets of Santiago, Chile, using a research platform implemented at the Robotics and Automation Laboratory of PUC to develop driver assistance systems.


Prolactinomas may have unusual presentations resulting from massive extrasellar tumor extension.
The purpose of this case series is to report eight patients with giant prolactinomas emphasizing presentations and a treatment complication. The study group included six men and two women. The median age was 29 years (18-54 years); median serum prolactin level was 4,562 ng/ml (1,543-18,690 ng/ml); three patients (37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41-60 mm). Five patients (62.5%) had visual field defects and three had improvement during treatment; six patients (75%) reached prolactin normalization, with a median time of 10.5 months (7-84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week). One patient presented as a true incidentaloma. One patient presented a cerebrospinal fluid leakage during medical treatment and refused surgery, however this resolved with conservative measures. This case series illustrate a rare subtype of macroprolactinomas, the importance of considering unusual presentations at the diagnosis, the effectiveness of pharmacological treatment and its possible complications.


An Improved Point-of-Care ELISA for the Diagnosis of Anaplasmosis and Ehrlichiosis During the Acute Phase of Tick-Borne Infections in Dogs.
Veterinarians often test for serologic evidence of vector-borne infections in sick dogs presenting with clinical signs or to screen for subclinical chronic infections. Additional peptide targets for the detection of antibodies to Anaplasma phagocytophilum, Anaplasma platys, and Ehrlichia canis were added to an existing point-of-care (POC) ELISA test (SNAP 4Dx Plus Test, IDEXX Laboratories, Westbrook, ME). This second-generation, multi-analyte test detects Dirofilaria immitis antigen and antibodies to Anaplasma spp., Borrelia burgdorferi, and Ehrlichia spp. The second-generation test is expected to better meet the needs of practicing veterinarians and their patients. To assess this expectation, the second-generation POC test was evaluated with serum samples from experimentally infected dogs and a broader field population of dogs. Compared to the first-generation test, most dogs experimentally infected with A phagocytophilum (n = 7/8), A platys (n = 4/6), or E canis (n = 4/6) had detectable antibody responses 3-22 days earlier post-infection; these results demonstrated better alignment with polymerase chain reaction (PCR) amplification results and the onset of clinical signs. Using a convenience sample set of 510 sera from both academic and commercial veterinary diagnostic laboratories, the second-generation test had sensitivities greater than 90% for Anaplasma spp. (94.1%), B burgdorferi (95.5%), Ehrlichia spp. (93.4%) and D immitis (98.0%). Specificity ranged from 96.8% - 100% across the four assays. Results from this study demonstrate that the second-generation POC ELISA had an improved ability to detect serologic responses during the acute phase of A phagocytophilum, A platys, and E canis experimental infections. The results from the broader field samples support overall high sensitivity and specificity, consistent with the historical performance of the first-generation POC ELISA test.


Association of prenatal counselling and immediate postnatal support with early initiation of breastfeeding in Uttar Pradesh, India.
Timely initiation of breastfeeding, also known as early initiation of breastfeeding, is a well-recognized life-saving intervention to reduce neonatal mortality. However, only one quarter of newborns in Uttar Pradesh, India were breastfed in the first hour of life. This paper aims to understand the association of community-based prenatal counselling and postnatal support at place of delivery with early initiation of breastfeeding in Uttar Pradesh, India. Data from a cross-sectional survey of 9124 eligible women (who had a live birth in 59 days preceding the survey) conducted in 25 districts of Uttar Pradesh, India, in 2018, were used. Simple random sampling was used to randomly select 40 Community Development Blocks (sub district administrative units) in 25 districts. The Primary Sampling Units (PSUs), health service delivery unit for frontline workers, were selected randomly from a linelisting of PSUs in each selected Community Development Block. Bivariate and multivariate logistic regression analyses were performed to assess the association of prenatal counselling and postnatal support on early initiation of breastfeeding in public, private and home deliveries. Overall 48.1% of mothers initiated breastfeeding within an hour, with major variation by place of delivery (61.2% public, 23.6% private and 32.6% home). The adjusted odds ratio (aOR) of early initiation of breastfeeding was highest among mothers who received both counselling and support (aOR 2.67; 95% CI 2.30, 3.11), followed by those who received only support (aOR 1.99; 95% CI 1.73, 2.28), and only counselling (aOR 1.40; 95% CI 1.18, 1.67) compared to mothers who received none. The odds of early initiation of breastfeeding was highest among mothers who received both prenatal counselling and postnatal support irrespective of delivery at public health facilities (aOR 2.49; 95% CI 2.07, 3.01), private health facilities (aOR 3.50; 95% CI 2.25, 5.44), or home (aOR 2.84; 95% CI 2.02, 3.98). A significant association of prenatal counselling and postnatal support immediately after birth on improving early initiation of breastfeeding, irrespective of place of delivery, indicates the importance of enhancing coverage of both the interventions through community and facility-based programs in Uttar Pradesh.


Broiler carcass bacterial counts after immersion chilling using either a low or high volume of water.
A study was conducted to investigate the bacteriological impact of using different volumes of water during immersion chilling of broiler carcasses. Market-aged broilers were processed, and carcasses were cut into left and right halves along the keel bone immediately after the final bird wash. One half of each carcass pair was individually chilled at 4 degrees C in a separate bag containing either 2.1 L/kg (low) or 16.8 L/kg (high) of distilled water. Carcass halves were submersed in a secondary chill tank containing approximately 150 L of an ice-water mix (0.6 degrees C). After chilling for 45 min, carcass halves were rinsed with 100 mL of sterile water for 1 min. Rinses and chill water were analyzed for total aerobic bacteria (APC), Escherichia coli, Enterobacteriaceae, and Campylobacter. After chilling with a low volume of water, counts were 3.7, 2.5, 2.6, and 2.1 log(10) cfu/mL of rinse for APC, E. coli, Enterobacteriaceae, and Campylobacter, respectively. When a high volume of chill water was used, counts were 3.2, 1.7, 1.6, and 1.8 log(10) cfu/mL of rinse for APC, E. coli, Enterobacteriaceae, and Campylobacter, respectively. There was no difference in bacterial counts per milliliter of chill water among treatments. These results show that using additional water during immersion chilling of inoculated broilers will remove more bacteria from the carcass surfaces, but numbers of bacteria per milliliter in the chiller water will remain constant. The bacteriological impact of using more water during commercial immersion chilling may not be enough to offset economic costs.


Evaluation of a surface imaging system's isocenter calibration methods.
AlignRT is a surface imaging system that has been utilized for localizing and tracking patient position during radiotherapy. AlignRT has two calibration procedures that can set the system's isocenter called "Monthly Calibration" (MC) and "Isocentre Calibration" (IC). The MC utilizes a calibration plate. In addition to the calibration plate, the IC utilizes a cubic phantom that is imaged with the linac treatment beam to aid in aligning the AlignRT and treatment-beam isocenters. This work evaluated the effects of misaligning the calibration plate during the calibration process. The plate was intentionally shifted away from isocenter ±3.0 mm in the longitudinal and lateral directions and ±1.0 mm in the longitudinal, lateral, and vertical directions. A mock stereotactic radiosurgery (SRS) treatment was used to evaluate the effects of the miscalibrations. An anthropomorphic head phantom was placed in an SRS treatment position and monitored with the AlignRT system. The AlignRT-indicated offsets were recorded at 270°, 315°, 0°, 45°, and 90° couch angles for each intentional misalignment of the calibration plate during the MC. The IC was also performed after each miscalibration, and the measurements were repeated and compared to the previous results. With intentional longitudinal and lateral shifts of ±3.0 mm and ±1.0 mm of the calibration plate, the average indicated offsets at couch rotations of ±90° were 4.3 mm and 1.6 mm, respectively. This was in agreement with the theoretical offset of √2*(shift-of-the-calibration plate). Since vertical shifts were along the rotation axis of the couch, these shifts had little effect on the offsets with changing couch angle. When the IC was applied, the indicated offsets were all within 0.5 mm for all couch angles for each of the miscalibrations. These offsets were in agreement with the known magnitude of couch walkout. The IC method effectively removes the potential miscalibration artifacts of the MC method due to misalignments of the calibration plate.


Epidemiological basis for clinical diagnosis of childhood malaria in endemic zone in West Africa.
It is difficult to distinguish childhood malaria from other common febrile disorders by parasite count alone, because of the wide variation in tolerance of parasitaemia among individuals. We postulated that the proportion of febrile episodes among young children that can be attributed to parasitaemia varies according to simple clinical criteria. We studied 1114 children aged 2-9 years, who attended a dispensary in the Republic of Niger, with a case-control approach; each of 557 febrile children was matched with a non-febrile control by sex, age, ethnic group, and day of presentation. Febrile episodes were classified according to three clinical criteria: the presence of a likely non-malarial cause; the duration (less than 3 or more than 3 days before presentation); and the intensity (below 39 degrees C or 39 degrees C and above). There was no evidence for an association between febrile episodes and parasite count during the dry, low-transmission, season. During the rainy, high-transmission, season, by contrast, there was a highly significant relation (p less than 0.0001) between the likelihood of fever and the parasite count; each clinical criterion strengthened the association. There was no association between parasitaemia and low intensity fevers, with an obvious cause, that started 3 or more days before presentation, even in the rainy season; however, the relative risk of a fever that met all three criteria developing in those with vs those without parasitaemia was 27.5. The proportion of febrile cases attributable to detectable parasitaemia (population attributable risk) ranged from 0 to 0.92. Our results suggest that simple clinical criteria may be valuable in the selection of febrile patients for antimalarial treatment. In this geographic area, high fever of short duration and with no other obvious cause that occurs during the rainy season is most likely to be malaria.


Digital poly-victimization: The increasing importance of online crime and harassment to the burden of victimization.
Many forms of victimization, including bullying and property crime, are increasingly moving online, but most studies of poly-victimization still primarily focus on in-person crime and violence. Few studies have examined the importance of incorporating technology-based victimizations for assessing the true burden of violence. The purpose of this study is to explore whether digital poly-victimization contributes to post-traumatic stress and anxiety/dysphoria symptoms after controlling for in-person poly-victimization. Given that technology use and technology-based victimization are changing rapidly, a mixed methods approach was adopted. In the first two phases, focus groups and cognitive interviews (89 total participants) were used to identify the range of digital victimization and develop the Digital Poly-Victimization Scale. In the third phase, the new measure was included in a community survey (n = 478, 57.5% female; 62.6% earning under $50,000 per year) in a rural Southern region, along with measures of in-person poly-victimization, posttraumatic stress and anxiety/dysphoria symptoms, and other outcomes and personal characteristics. A comprehensive measure of digital poly-victimization indicated that almost 3 in 4 participants (72.3%) had experienced at least one form of digital victimization. The results indicated that digital poly-victimization contributed unique variance to post-traumatic stress and anxiety/dysphoria symptoms (p < .001), health-related quality of life (p < .01), and subjective and family well-being (both p < .001), even after controlling for demographics and in-person poly-victimization. Digital victimization often presents fewer risks to perpetrators and can be expected to represent an increasing share of the societal burden of violence. Future research on poly-victimization should pay more attention to the role of digital victimization.


Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas.
Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on gray and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients. We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with gray and white matter volumes within the patient group. Patients compared to controls had significantly reduced gray matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller gray matter volumes in the posterior cingulate cortex. Our data provide the first evidence that hypothalamic tumor involvement impacts gray and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e., deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone.


Ca2+,Mg2+-ATPase of microsomal membranes from bovine aortic smooth muscle. Identification and characterization of an acid-stable phosphorylated intermediate of the Ca2+,Mg2+-ATPase.
An acid-stable phosphoprotein was formed in a microsomal membrane fraction isolated from bovine aortic smooth muscle in the presence of Mg2+ + ATP and Ca2+. The microsomes also showed Ca2+ uptake activity. The Ca2+ dependence of phosphoprotein formation and of Ca2+ uptake occurred over the same range of Ca2+ concentration (1-10 microM), and resembled similar findings from rabbit skeletal microsomes. The molecular weight of the phosphorylated protein, estimated by SDS-gel electrophoresis, was approximately 105,000. The phosphoprotein was labile at alkaline pH, and its decomposition was accelerated by hydroxylamine. Half-maximum incorporation of 32P in the presence of 10 microM Ca2+ occurred at 60 nM ATP. The calcium-dependent phosphoprotein formation was not affected by 5 mM NaN3, but was inhibited in a dose-dependent fashion by ADP with a 50% inhibition occurring at 180 microM. Fifty mM MgCl2 was required for the maximal phosphorylation. The rate of phosphoprotein decomposition after adding 2 mM EGTA was accelerated by varying the Mg2+ concentration from 10 microM to 3 mM. Alkaline pH (9.0) slowed the rate of phosphoprotein decay. Optimal Ca2+-dependent phosphoprotein occurred at 15 degrees C over a broad pH range (6.4 to 9.0). The activation energy of EGTA-induced phosphoprotein decomposition was 25.6 kcal/mol between 0 and 16 degrees C and 14.6 kcal/mol between 16 and 30 degrees C. The phosphoprotein formed by aortic microsomes was thus quite similar to the acid-stable phosphorylated intermediate of the Ca2+-transport ATPase of sarcoplasmic reticulum from skeletal and cardiac muscle. These data suggest that the Ca2+-dependent phosphoprotein is a reaction intermediate of the Ca2+,Mg2+-ATPase of the aortic microsomes.


A distance-based dynamical transition analysis of time series signals and application to biological systems.
This study demonstrates an application of distance-based numerical measures to the phase space of time series signals, in order to obtain a temporal analysis of complex dynamical systems. This method is capable of detecting alterations appearing in the characters of the deterministic dynamical systems and provides a simple tool for the real-time analysis of time series data obtained from a complex dynamical system even with black box functionality. The study presents a possible application of the method in the dynamical transition analysis of real EEG records from epilepsy patients.


Invited article: Time accurate mass flow measurements of solid-fueled systems.
A novel diagnostic method is described that utilizes a thrust stand mass balance (TSMB) to directly measure time-accurate mass flow from a solid-fuel thruster. The accuracy of the TSMB mass flow measurement technique was demonstrated in three ways including the use of an idealized numerical simulation, verifying a fluid mass calibration with high-speed digital photography, and by measuring mass loss in more than 30 hybrid rocket motor firings. Dynamic response of the mass balance was assessed through weight calibration and used to derive spring, damping, and mass moment of inertia coefficients for the TSMB. These dynamic coefficients were used to determine the mass flow rate and total mass loss within an acrylic and gaseous oxygen hybrid rocket motor firing. Intentional variations in the oxygen flow rate resulted in corresponding variations in the total propellant mass flow as expected. The TSMB was optimized to determine mass losses of up to 2.5 g and measured total mass loss to within 2.5% of that calculated by a NIST-calibrated digital scale. Using this method, a mass flow resolution of 0.0011 g/s or 2% of the average mass flow in this study has been achieved.


Ultrasonographic Detection of Airway Obstruction in a Model of Obstructive Sleep Apnea.
Purpose Obstructive sleep apnea (OSA) is a common clinical disorder characterized by repetitive airway obstruction during sleep. The gold standard for diagnosis of OSA, polysomnogram (PSG), cannot anatomically localize obstruction. Precise identification of obstruction has potential to improve outcomes following surgery. Current diagnostic modalities that provide this information require anesthesia, involve ionizing radiation or disrupt sleep. To mitigate these problems, we conceived that ultrasound (US) technology may be adapted (i) to detect, quantify and localize airway obstruction and (ii) for translational application to home-based testing for OSA. Materials and Methods Segmental airway collapse was induced in 4 fresh cadavers by application of negative pressure. Following visualization of airway obstruction, a rotary US probe was used to acquire transcervical images of the airway before and after induction of obstruction. These images (n=800) were analyzed offline using image processing algorithms. Results Our results show that the non-obstructed airway consistently demonstrated the presence of a US air-tissue interface. Importantly, automated detection of the air-tissue interface strongly correlated with manual measurements. The algorithm correctly detected an air-tissue interface in 90% of the US images while incorrectly detecting it in 20% (area under the curve=0.91). Conclusion The non-invasive detection of airway obstruction using US represents a major step in expanding OSA diagnostics beyond PSG. The preliminary data obtained from our model could spur further research in non-invasive localization of obstruction. US offers the benefit of precise localization of the site of obstruction, with potential for improving outcomes in surgical management.


Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.
Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.


Deletion of the vaccinia virus N2L gene encoding an inhibitor of IRF3 improves the immunogenicity of modified vaccinia virus Ankara expressing HIV-1 antigens.
A modified vaccinia virus Ankara poxvirus vector expressing the HIV-1 Env, Gag, Pol, and Nef antigens from clade B (MVA-B) is currently being tested in clinical trials. To improve its immunogenicity, we have generated and characterized the immune profile of MVA-B containing a deletion of the vaccinia viral gene N2L, which codes for an inhibitor of IRF3 (MVA-B ΔN2L). Deletion of N2L had no effect on virus growth kinetics or on the expression of HIV-1 antigens; hence, the N2 protein is not essential for MVA replication. The innate immune responses triggered by MVA-B ΔN2L revealed an increase in beta interferon, proinflammatory cytokines, and chemokines. Mouse prime-boost protocols showed that MVA-B ΔN2L improves the magnitude and polyfunctionality of HIV-1-specific CD4(+) and CD8(+) T cell adaptive and memory immune responses, with most of the HIV-1 responses mediated by CD8(+) T cells. In the memory phase, HIV-1-specific CD8(+) T cells with an effector phenotype were predominant and in a higher percentage with MVA-B ΔN2L than with MVA-B. In both immunization groups, CD4(+) and CD8(+) T cell responses were directed mainly against Env. Furthermore, MVA-B ΔN2L in the memory phase enhanced levels of antibody against Env. For the vector immune responses, MVA-B ΔN2L induced a greater magnitude and polyfunctionality of VACV-specific CD8(+) T memory cells than MVA-B, with an effector phenotype. These results revealed the immunomodulatory role of N2L, whose deletion enhanced the innate immunity and improved the magnitude and quality of HIV-1-specific T cell adaptive and memory immune responses. These findings are relevant for the optimization of poxvirus vectors as vaccines. On the basis of the limited efficacy of the RV144 phase III clinical trial, new optimized poxvirus vectors as vaccines against HIV/AIDS are needed. Here we have generated and characterized a new HIV/AIDS vaccine candidate on the basis of the poxvirus MVA vector expressing HIV-1 Env, Gag, Pol, and Nef antigens (MVA-B) and containing a deletion in the vaccinia virus N2L gene. Our findings revealed the immunomodulatory role of N2L and proved that its deletion from the MVA-B vector triggered an enhanced innate immune response in human macrophages and monocyte-derived dendritic cells. Furthermore, in immunized mice, MVA-B ΔN2L induced improvements in the magnitude and quality of adaptive and memory HIV-1-specific CD4(+) and CD8(+) T cell immune responses, together with an increase in the memory phase of levels of antibody against Env. Thus, the selective deletion of the N2L viral immunomodulatory gene is important for the optimization of MVA vectors as HIV-1 vaccines.


Aripiprazole salts. II. Aripiprazole perchlorate.
The molecular structure of aripiprazole perchlorate (systematic name: 4-(2,3-dichlorophenyl)-1-{4-[(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)oxy]butyl}piperazin-1-ium perchlorate), C(23)H(28)Cl(2)N(3)O(2)(+)·ClO(4)(-), does not differ substantially from the recently published structure of aripiprazole nitrate [Freire, Polla & Baggio (2012). Acta Cryst. C68, o170-o173]. Both compounds have almost identical bond distances, bond angles and torsion angles. The two different counter-ions occupy equivalent places in the two structures, giving rise to very similar first-order `packing motifs'. However, these elemental arrangements interact with each other in different ways in the two structures, leading to two-dimensional arrays with quite different organizations.


The impact of prenatal exposure to a single dose of testosterone on insulin resistance, glucose tolerance and lipid profile of female rat's offspring in adulthood.
In our previous study, we introduced a rat model of polycystic ovary syndrome (PCOS) induced by prenatal exposure to a single dose of testosterone on embryonic day 20. In the current study, we aimed to investigate whether prenatal exposure to a single dose of testosterone could also induce metabolic disturbances, especially insulin resistance in adulthood (100-110 days of age) and also to make it as an appropriate rat model of PCOS (exhibiting both reproductive and metabolic disturbances with minimum morphological disorders in reproductive system) for further studies in PCOS. Pregnant rats in the experimental group were subcutaneously injected with 5 mg free testosterone on the gestational day 20, while controls received only the solvent. Female offspring of both groups, prenatally androgenized (PNA) rats (PCOS models of rats) and controls were examined. Body weight measures showed significant increase in the PNA rats compared to controls on days 30, 45, 60 of age and in adulthood (P < 0.05). PNA rats showed insulin resistance compared to controls. Impaired glucose tolerance was not observed in the PNA rats compared to controls. There were no significant differences in lipid profile between the PNA and control rats (P > 0.05). Our study suggests that metabolic disturbances in PCOS and their severity during adult life probably depend on the particular time and levels of prenatal androgen exposure.


Facing real-life with direct oral anticoagulants in patients with nonvalvular atrial fibrillation: outcomes from the first observational and prospective study in a Spanish population.
To analyze the effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients attended in clinical practice. Observational and prospective study of AF patients that started treatment with DOACs. 1443 patients (age 77.2 ± 9.7 years, CHA2DS2-VASc = 4.1 ± 1.5) were included. 46.0% were taking rivaroxaban, 24.4% dabigatran, 22.5% apixaban and 7.1% edoxaban. Patients taking dabigatran were younger, had lower CHA2DS2-VASc and lesser renal insufficiency. Patients taking apixaban had higher CHA2DS2-VASc and more renal insufficiency. Rates of stroke/major bleeding/intracranial bleeding were 0.7/1.3/0.2 events/100 patient-years, respectively. This was the first prospective study that analyzed the use of all DOACs in AF patients in Spain, showing a good profile in terms of safety and effectiveness in accordance with pivotal studies.


General health status and changes in chewing ability in older Canadians over seven years.
The purpose of this study was to describe the onset of and recovery from chewing problems in an older adult population over a seven-year period and to describe factors associated with these changes. Of particular interest was the relationship between general health and changes in oral functioning. The data came from a longitudinal study of community-dwelling individuals who were aged 50 years and older when first recruited. Data were collected at baseline (n = 907) and at three (n = 611) and seven-year (n = 425) follow-ups. Oral function was assessed by means of a six-item index of chewing ability. Data were weighted to account for loss to follow-up using weights derived from the seven-year response proportions for dentate and edentulous subjects. Logistic regression analysis using backward stepwise selection was used to identify predictors of onset and recovery. At baseline, 25 percent of subjects reported a problem chewing. This rose to 26 percent at three years and 34 percent at seven years. The seven-year incidence of chewing dysfunction was 19 percent. Of those with a chewing problem at baseline, 21 percent did not have a problem at seven years. A logistic regression model predicting the seven-year incidence of chewing problems indicated that subjects aged 65 years or older, the edentulous, those rating their oral health as poor, those without dental insurance and those without a regular source of dental care were more likely to be an incident case. In addition, a variable denoting the number of chronic medical conditions at baseline also entered the model. A logistic regression model predicting recovery indicated that older subjects, the edentulous, those from low-income households, and those with limitations in activities of daily living were less likely to recover over the observation period. The results of this study indicate a marked increase in the prevalence of chewing problems in this older adult population over the seven-year observation period. Poorer general health at baseline increased the probability of the onset of a chewing problem and decreased the probability of recovery.


Decisions and the evolution of memory: multiple systems, multiple functions.
Memory evolved to supply useful, timely information to the organism's decision-making systems. Therefore, decision rules, multiple memory systems, and the search engines that link them should have coevolved to mesh in a coadapted, functionally interlocking way. This adaptationist perspective suggested the scope hypothesis: When a generalization is retrieved from semantic memory, episodic memories that are inconsistent with it should be retrieved in tandem to place boundary conditions on the scope of the generalization. Using a priming paradigm and a decision task involving person memory, the authors tested and confirmed this hypothesis. The results support the view that priming is an evolved adaptation. They further show that dissociations between memory systems are not--and should not be--absolute: Independence exists for some tasks but not others.


4-(1-Benzyl-1H-benzo[d]imidazol-2-yl)-4-oxo-2-butenoic Acid Derivatives: Design, Synthesis and Anti-HIV-1 Activity.
Acquired immunodeficiency syndrome (AIDS) is still an incurable disease with increasing mortality rate. Despite the development of effective FDA-approved anti-HIV drugs, there are some problems due to the growing of resistant viral strands. Therefore, discovery of novel anti-HIV agents is so needed. Integrase, targeted in highly active antiretroviral therapy (HAART), is a crucial enzyme in viral replication. In this study, new benzimidazolyl diketo acid derivatives were designed according to required features for inhibitors of HIV-1 integrase. Designed compounds were synthesized and evaluated for anti-HIV-1 effects. According to the cell-based biological assay's results, most of the tested compounds demonstrated good anti-HIV-1 activity, ranging from 40-90 µM concentration with no severe cytotoxicity. The most potent compound was 13g with EC50 value of 40 µM and CC50 value of 550 µM. Docking analysis of compound 13g in integrase active site was in good agreement with well-known integrase inhibitors, proposing that anti-HIV-1 potency of compounds may be via integrase inhibition.


Use of a disclosed plaque visualization technique improved the self-performed, tooth brushing ability of primary schoolchildren.
Disclosing agents have a long history of use as an aid in children's tooth brushing instruction. However, their benefit when used to improve self-performed tooth brushing ability without any tooth brushing instruction has not been investigated. To evaluate the effect of disclosed plaque visualization on improving the self-performed, tooth brushing ability of primary school children. A cluster-randomized, crossover study was conducted in Nakhon Nayok province, Thailand. A total of 122 second-grade schoolchildren, aged 8-10 years old, from 12 schools were randomly divided into 2 groups. The first group was assigned to brush with disclosed plaque visualization, while the other group brushed without disclosed plaque visualization. One month later the groups switched procedures. Tooth brushing ability was evaluated by the subjects' reduction in patient hygiene performance (PHP) scores. The data were analyzed using repeated-measures analysis of variance, with significance set at p<0.05. Disclosed plaque visualization had a significant effect on improving the children's self-performed, tooth brushing ability in all areas of the mouth (p<0.001), particularly for anterior teeth, mandibular teeth, buccal surfaces, and areas adjacent to the gingival margin (p<0.001). Disclosed plaque visualization is a viable technique to improve children's self-performed tooth brushing ability, and could be used in school-based oral health promotion programs.


Promoting Health Literacy in the Nonsurgical Cosmetic Patient.
Significant numbers of adults, when presented with basic health care information, have been shown to struggle with their abilities to comprehend and integrate materials presented to them. This lack of perception underscores the essence of health literacy. Even though health literacy is a newer concept, its impact is gathering momentum, as politicians, health care providers, researchers, and the media become more aware of the extent this disparity is seen within the health care system and how it affects patient care. This article explores how nursing philosophy and knowledge development have the capacity to provide a solid infrastructure that may promote increased health literacy among patients within the nonsurgical cosmetic arena.


Ankle Mortise Instability in Multiple Hereditary Exostoses.
Ankle valgus is commonly reported in patients with multiple hereditary exostoses (MHE). We report the characteristics of mortise widening in MHE, its progression over time, and the resultant ankle pain and function at skeletal maturity. Mortise medial space (M), talocrural angle (TC), and tibiotalar angle (TT) measurements were collected on preoperative and last follow-up radiographs. Operative data and complications were recorded. American Orthopaedic Foot and Ankle Society (AOFAS) and short form-36 scores at skeletal maturity were collected. A total of 16 patients (19 ankles) had MHE and mortise widening. Thirteen patients had surgery. Preoperatively, no patient complained of instability. However, 11 ankles (57.9%) were painful and 15 (78.9%) were clinically in valgus. Patients underwent surgery at a mean age of 11.8 ± 2.2 y. Operative interventions included medial distal tibia hemiepiphysiodesis for the majority of patients. There were no statistically significant differences between pre and postoperative M, TC, TT angles. Operative patients showed an improved mean M (5.17 ± 1.17 to 4.63 ± 1.06 mm) and TT (8.71 ± 5.40° to 4.54 ±7.58°), however, neither angle reached normal values. TC representing fibular length-maintained measurements within normal limits (82.2 ± 5.3° to 84.8 ±5.8°). Questionnaires were obtained for 10 (52.6%) ankles. Mean age at questionnaires collection was 19.0 ± 3.6 y. Mean AOFAS score was 74.8 ± 17.6 out of 100. Patients scored 6.5 ± 4.1 out of 10 for alignment, 33.0 ± 6.7 out of 40 for pain, 35.3 ± 9.5 out of 50 for function. All short form-36 scores were above the national mean. Improvement of M and TT angles was modest. TC angle was within normal limits but showed an overall fibular shortening and decreased lateral buttress and potential for talar shift, as reflected in AOFAS score. The underwhelming amount of mortise widening correction achieved may not provide for a stable ankle joint.


Polycarbazole nanocomposites with conducting metal oxides for transparent electrode applications.
The preparation and characterization of conducting polycarbazole (PCz) hybrid films with a colorless transparency are described. They were prepared by the vacuum evaporation of tin, aluminum, or gallium onto anion-doped green-colored PCz films, or by applying gallium to the films, followed by their exposure to ambient air. The resultant hybrid films consisting of an undoped PCz backbone and metal compounds exhibited good transparencies (90-95% at a wavelength of 550 nm). The hybrid films have a specific cross-sectional structure in which the small regions of the metal compounds are dispersed in the PCz backbone. The hybridization reaction was mechanistically explained on the basis of the combination of a metal corrosion reaction and polymer dedoping reaction, which was successfully supported by the chemical analyses of the hybrid films. The electric conductivities of the hybrid films, measured by a four-point-probe method, ranged from 2.2 x 10(-4) to 6.0 x 10(-3) S cm(-1), which are considered to be the lowest limit because the use of the hybrid films as an electrochemical electrode reveals that a network of conductive paths is preferentially formed in the film thickness direction rather than in the in-plane direction.


Common cancers in centenarians.
A Centenarian is a person who attains and lives beyond the age of 100. Four percent of centenarians die from cancer. It is therefore important to understand which cancers affect them in order to devise better methods to prevent and treat them. The aim of this study was to investigate the top cancers that affect centenarians. We identified 1385 cases with the Surveillance Epidemiology and End Result (SEER) database. Our study included centenarians age 100-115 years diagnosed with the 5 most common cancers between 1973 and 2007 in the United States. Observed survival (OS) was calculated for each cancer type. The Kaplan-Meier (KM) method was used to calculate OS at 1-month intervals for the first 40 months after diagnosis using SEER*Stat version 7.04. A log rank test was performed on KM survival output and a Cox proportional hazard model was used to calculate hazard ratios. All statistical analyses were performed with 95% confidence intervals with significance determined at P<0.05. Cox proportional hazard analysis was done using GraphPad Prism version 5.04. There were 879 (63.47%) females and 506 (36.53%) males. There were 1118 (80.72%) whites, 159 (11.48%) blacks, and 108 (7.80%) other. The top cancers were 405 (29.24%) breast, 267 (19.28%) colorectal, 254 (18.34%) prostate, 247 (17.83%) lung and bronchus, and 212 (15.31%) urinary and kidney cancer cases. As the prevalence of centenarians increases, it is becoming increasingly important to become aware of the cancers that affect them in order to better manage them.


Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.
Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.


Text or Not to Text? A Narrative Review of Texting as a Case Management Intervention.
To review current literature on texting as a sustainable intervention of case management in the outpatient setting. Texting, as a case management intervention, provides the medically complex client with a pathway to achieve care plan goals. Texting increases adherence, communication, and self-management. It can increase client enrollment in disease management programs, while providing support, flexibility, convenience, cost savings, and increased participation. In current practice, such as management of the coronavirus (COVID-19), other pandemics, or natural/environmental disasters, texting is a solution-focused intervention that can deliver and retrieve real-time information to a medically complex population. It can link patients to resources and increase outreach, efficiency, quality, and coordination of care. Texting can promote adherence to appointments, increase medication compliance and disease management interventions, and provide motivational change messages. However, there are legal and regulatory concerns that carry potential consequences and implications that should be approached judiciously (Mellette, 2015). Texting is not one size fits all; it can cause HIPAA breeches, hinder communication with certain populations, confuse health messaging, and replace human communication, thereby reducing staffing in practice.


Helping learners level up with cognitive supports.
This column describes strategies for helping educators and trainers address common problems with executive functioning and memory for their audiences, to better facilitate learning. The purpose of the article is to suggest strategies for maximizing learning and goal achievement for students in academic settings, as well as for building employee knowledge and skills in the psychiatric rehabilitation workforce through worksite-based training. The content in this column is drawn from the professional experience of the authors as well as available literature. Educators and trainers encounter many challenges when assisting people to achieve desired learning objectives. Attending to the cognitive needs of all learners, by supporting their planning, attention, memory, and reasoning skills, can minimize some of these challenges. Educators and trainers may implement the strategies described to better engage with their audiences, whether in an academic or clinical practice environment. Implementation of specific strategies to offset limitations will positively affect all learners, who benefit both from maximized knowledge and skill acquisition as well as improved job performance. Improved learning will likely translate to better practitioner skill over time, which should lead to improved outcomes for service users in the field of psychiatric rehabilitation. (PsycINFO Database Record


Xanthohumol Attenuates Lipopolysaccharide-Induced Depressive Like Behavior in Mice: Involvement of NF-κB/Nrf2 Signaling Pathways.
Depression is the most common psychiatric disorder associated with brain and immune system abnormalities. In recent years, xanthohumol (Xn) a bioactive prenylated flavonoid has received ample attention for its polypharmacological effects, therefore, here we aimed to explore the protective effects of Xn against the LPS-induced depressive-like symptoms mediated by inflammation and oxidative stress. We tested the effect of Xn against LPS-induced behavioural changes in mice by means of forced swimming test (FST), tail suspention test (TST), sucrose preference test (SPT) and open field test (OPT). Examined the neuroinflammation and oxido-nitrosative stress (O&NS) markers and analyze Nrf2 and NF-κB signalling pathways in the hippocampus. Our results indicated that peripheral repeated administration of lipopolysaccharides (LPS) (1 mg/kg, intra peritoneally) induced depressive-like behavior, neuroinflammation and O&NS in mice. Pretreatment with Xn (10 and 20 mg/kg, intra gastrically) reverse the behavioural impairments prophylactically as obvious in the FST and TST without effecting locomotion, however only 20 mg dose improve anhedonic behavior as observed in SPT. Similarly, Xn pretreatment in dose-dependent manner prevented the LPS induced neuro-inflammation and O&NS. Immunofluorescence analysis showed that Xn reduced activated gliosis via attenuation of Iba-1 and GFAP in hippocampus. In addition, Xn considerably reduced the expression of phospho-NF-κB and cleaved caspase-3 while enhanced Nrf2 and HO-1 expression in the hippocampus. To the best of our knowledge, this is the first study to examine the underlying beneficial prophylactic effects of the Xn in neuroinflammation and O&NS mediating depressive-like behaviors.


30-, 31-, and 32-hydroxybullatacinones: bioactive terminally hydroxylated annonaceous acetogenins from Annona bullata.
From Annona bullata, three more pairs of new ketolactone Annonaceous acetogenins were isolated by bioactivity-directed isolation. They are hydroxylated adjacent bistetrahydrofuran (THF) acetogenins and are named (2,4-cis and trans)-32-hydroxybullatacinone (1 and 2), (2,4-cis and trans)-31-hydroxybullatacinone (3 and 4), and (2,4-cis and trans)-30-hydroxybullatacinone (5 and 6). The structures were elucidated by analysis of the 1H- and 13C-nmr spectra of 1-6 and their acetates and the ms of their tri-trimethylsilyl (TMSi) derivatives as compared with bullatacinone [7]. This is the first time that Annonaceous acetogenins with OH groups at successive positions near the end of the aliphatic chain have been reported. All of the new compounds showed potent activities in the brine shrimp lethality test and against human solid tumor cells in culture, with selectivities exhibited especially toward the colon cancer cell line (HT-29).


Restoration of Epithelial Sodium Channel Function by Synthetic Peptides in Pseudohypoaldosteronism Type 1B Mutants.
The synthetically produced cyclic peptides solnatide (a.k.a. TIP or AP301) and its congener AP318, whose molecular structures mimic the lectin-like domain of human tumor necrosis factor (TNF), have been shown to activate the epithelial sodium channel (ENaC) in various cell- and animal-based studies. Loss-of-ENaC-function leads to a rare, life-threatening, salt-wasting syndrome, pseudohypoaldosteronism type 1B (PHA1B), which presents with failure to thrive, dehydration, low blood pressure, anorexia and vomiting; hyperkalemia, hyponatremia and metabolic acidosis suggest hypoaldosteronism, but plasma aldosterone and renin activity are high. The aim of the present study was to investigate whether the ENaC-activating effect of solnatide and AP318 could rescue loss-of-function phenotype of ENaC carrying mutations at conserved amino acid positions observed to cause PHA1B. The macroscopic Na+ current of all investigated mutants was decreased compared to wild type ENaC when measured in whole-cell patch clamp experiments, and a great variation in the membrane abundance of different mutant ENaCs was observed with Western blotting experiments. However, whatever mechanism leads to loss-of-function of the studied ENaC mutations, the synthetic peptides solnatide and AP318 could restore ENaC function up to or even higher than current levels of wild type ENaC. As therapy of PHA1B is only symptomatic so far, the peptides solnatide and AP318, which directly target ENaC, are promising candidates for the treatment of the channelopathy-caused disease PHA1B.


Topological insulators from a chemist's perspective.
Heavy stuff: Topological insulators are formed of heavy atoms and host special surface or edge states. The electronic structure is characterized by a Dirac cone within a bulk band gap (see picture) that is generated by strong spin-orbit coupling. A chemist's perspective in terms of bonds, bands, symmetry, and nuclear charge is provided.


Gastric bypass surgery contributing to hyperammonaemic encephalopathy: an under-reported cause of severe nutritional deficiency and significant patient mortality.
Gastric-bypass associated hyperammonaemia (GaBHA) is an under-recognised cause of non-hepatic encephalopathy that is associated with significant mortality and has limited reporting in published literature. GaBHA has been reported predominately in middle-aged females with a past surgical history of Roux-En-Y surgical procedure. Individuals may present at any stage post-surgery and an important minority may have an undiagnosed inherited metabolic disorder. We report a case of a 49 year old woman who presented acutely with encephalopathy, a significantly elevated plasma ammonia level, and substantial multifactorial nutritional deficiency which required correction with intensive enteral and parenteral nutritional support. This case represented a diagnostic and management challenge for acute medical physicians and the multidisciplinary team involved.


Fatty acid desaturase regulation in adipose tissue by dietary composition is independent of weight loss and is correlated with the plasma triacylglycerol response.
Atherogenic dyslipidemia associated with elevated plasma triacylglycerol concentrations and reduced HDL is improved by both caloric restriction and reduced carbohydrate consumption. We aimed to identify the molecular pathways responsive to both caloric restriction and dietary composition within adipose tissue by monitoring transcriptional expression. Subcutaneous adipose tissue biopsy specimens were obtained from 131 moderately overweight men [body mass index (in kg/m2): 29.2 +/- 2.0] after 1 wk of a basal diet [54%, 16%, and 30% carbohydrate, protein, and fat, respectively; 7% saturated fat), after 3 wk with 1 of 4 randomized diets [basal diet; moderate-carbohydrate (39%) diet; low-carbohydrate (26%) and low-saturated-fat (9%) diet; low-carbohydrate (26%) and high-saturated-fat (15%) diet], after 5 wk of acute weight loss with a randomized diet (-1103.0 +/- 216.5 kcal/d, which resulted in a loss of 10.0 +/- 3.3 lb, or 4.5 +/- 1.5 kg), and after 4 wk of being stabilized at a reduced weight. Transcriptional response was identified by using expression array analysis and was confirmed by using real-time polymerase chain reaction analysis. Of the 1473 transcripts significantly decreased in expression in response to acute weight loss, 30 were responsive to isocaloric alterations in dietary composition, including stearoyl-coenzyme A desaturase (SCD), fatty acid desaturases 1 and 2 (FADS1 and FADS2), and diacylglycerol transferase 2 (DGAT2). Response was confirmed by real-time polymerase chain reaction analysis for these genes (P < 0.003). SCD expression in response to isocaloric dietary change was most strongly correlated with carbohydrate intake (P = 0.019) and, with the low-carbohydrate diet, SCD expression was inversely correlated with saturated fat intake (P = 0.05). Triacylglycerol responses to changes in dietary composition were independently correlated with SCD (P = 0.003) and DGAT2 (P = 0.05) responses. SCD expression in adipose tissue is independently regulated by weight loss and by carbohydrate and saturated fat intakes. Moreover, SCD and DGAT2 expression may be involved in dietary regulation of systemic triacylglycerol metabolism.


Anaesthesia for open wrist fracture surgery in adults/elderly.
Anaesthetic technique for open surgery of acute distal for arm fracture in adults/elderly is not well defined. Regional anaesthesia, general anaesthesia or a combined general and regional block may be considered. General anaesthetic technique, the timing and drug/drug combination for the regional block must also be considered. This is a study around published studies assessing anaesthtic technique for wrist surgery. A systematic database search was performed and papers describing the effect of anaesthetic techniques were included. We found sparse evidence for what anaesthetic technique is optimal for open wrist fracture repair. In total only six studies were found using our inclusion criteria, which all supported the short term, early recovery benefits of regional anaesthesia as part of multi-modal analgesia. More protracted outcomes and putting the type of block into context of quality of recovery and patients' satisfaction is lacking in the literature. The risk for a pain rebound when the block vanishes should also be acknowledged. Therefore, further high quality studies are warranted concerning the anaesthetic technique for this type of surgery.


Kinetics of hydrogen atom transfer from (eta(5)-C(5)H(5))Cr(CO)(3)H to various olefins: influence of olefin structure.
Treating (etha(5)-C(5)H(5))Cr(CO)3H (1) or (etha(5)-C(5)H(5))Cr(CO)3D (1-d(1)) with an excess of olefin containing the opposite isotope generally leads to H/D exchange, although hydrogenation is also observed in some cases. Application of an appropriate statistical correction to the observed exchange rate gives kH and kD, the rate constants for H* (D*) transfer from (etha(5)-C(5)H(5))Cr(CO)(3)H (D) to various olefins. The values of kH and kD vary appreciably with the substituents on the double bond. Phenyl-substituted olefins accept H* more readily than do carbomethoxy-substituted olefins, although the latter accept H* more readily than do alkyl-substituted olefins. A methyl substituent on the incipient radical site increases k(H) at 323 K by a factor between 5 and 50. A methyl substituent on the carbon to which the H* is being transferred decreases kH substantially. On the whole, the rate constants for H* transfer reflect steric effects as well as the stability of the resulting carbon-centered radicals.


The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway.
Members of the c-Jun NH(2)-terminal kinase (JNK) family play crucial roles in cell activation, differentiation, and apoptosis. Although many studies have indicated that JNK1 and JNK2 have functional differences and redundancy, the upstream signaling pathway that selectively activates JNK1 or JNK2 remains unknown. In this study, we have revealed a selective mechanism of JNK activation, in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10-mediated JNK2 activation had a critical role in regulating the amount of c-Jun protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are differentially regulated in the TCR-signaling pathway and play different functions.


Is thrombolysis of occluded popliteal and tibial bypass grafts worthwhile?
We analyzed the short- and long-term results for patients undergoing thrombolysis of occluded infrainguinal bypass grafts at our institution over a 62-month period. Thirty-one patients with 40 episodes of graft thrombosis in 33 grafts managed by thrombolysis were retrospectively reviewed. The effects of graft age, material, and anatomy, symptoms, treatment, anticoagulation, and occlusion duration were evaluated for impact on patency after thrombolysis. Dose and duration of therapy with use of the technique of pulse-spray thrombolysis was assessed. Thrombolysis successfully reestablished patency in 92% of grafts treated. Mean lysis time and urokinase dose were 118 minutes and 607,000 units, respectively. Responsible lesions were identified and treated by angioplasty or surgery in 35 of 37 cases. The patency rate after thrombolysis was 28% at 30 months, and the secondary patency rate was 46% at 18 months. Duration of occlusion, symptoms, treatment, graft anatomy, and prior graft revision did not impact on patency. Mean secondary patency was 21.5 months in grafts in place over 1 year and 7.0 months in grafts in place for less than 1 year. Mean secondary patency was 23.8 months in polytetrafluoroethylene grafts and 8.4 months in vein grafts. The limb salvage rate was 84% at 30 months, and the patient survival rate was 84% at 42 months. Pulse-spray thrombolysis is effective in rapidly recanalizing thrombosed infrainguinal grafts. Grafts failing in the first year after placement should generally be replaced, reserving thrombolysis and revision for grafts greater than 1 year old. Vein grafts tolerate thrombosis less well than synthetic conduits and have decreased long-term patency.


Restoring lepidopteran diversity in a tropical dry forest: relative importance of restoration treatment, tree identity and predator pressure.
Tropical dry forests (TDFs) have been widely transformed by human activities worldwide and the ecosystem services they provide are diminishing. There has been an urgent call for conservation and restoration of the degraded lands previously occupied by TDFs. Restoration experiences aim to recover species diversity and ecological functions. Different restoration strategies have been used to maximize plant performance including weeding, planting or using artificial mulching. In this investigation, we evaluated whether different restoration practices influence animal arrival and the reestablishment of biotic interactions. We particularly evaluated lepidopteran larvae diversity and caterpillar predation on plants established under different restoration treatments (mulching, weeding and control) in the Pacific West Coast of México. This study corroborated the importance of plant host identity for lepidopteran presence in a particular area. Lepidopteran diversity and herbivory rates were not affected by the restoration treatment but they were related to tree species. In contrast, caterpillar predation marks were affected by restoration treatment, with a greater number of predation marks in control plots, while caterpillar predation marks among plant species were not significantly different. This study highlights the importance of considering the introduction of high plant species diversity when planning TDF restoration to maximize lepidopteran diversity and ecosystem functioning.


Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.
Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.


Influence of heart rate in the selection of the optimal reconstruction window in routine clinical multislice coronary angiography.
The aim of our study was to assess the influence of heart rate on the selection of the optimal reconstruction window with 40-slice multidetector-row computed tomography (40-MDCT) coronary angiography. We studied 170 patients (114 men, age 60+/-11.3 years) with suspected or known coronary artery disease with 40-MDCT coronary angiography. Patients [mean heart rate (HR) 62.9+/-9.3 bpm, range 42-94 bpm] were clustered in two groups (group A: HR <or=65 bpm; group B: HR >65 bpm). Multiphase reconstruction data sets were obtained with a retrospective electrocardiogram (ECG)-gated 40-MDCT coronary angiography scan from 0% to 95% every 5% of the R-R interval. Two radiologists in consensus evaluated the best data sets for diagnostic purposes. In group A, the optimal reconstruction windows were at 70% (55/110, 71/110 and 69/110 for the right coronary artery, left anterior descending and the left circumflex, respectively) and 75% (26/110, 28/110 and 28/110, respectively) of the R-R interval. In group B, a wide range of reconstruction windows were employed, both in the end-systolic phase at 40% (32/60, 18/60 and 17/60, for the right coronary artery, left anterior descending and circumflex, respectively) and diastolic phases at 70% (12/60, 22/60 and 19/60, respectively). Six scans were excluded due to severe respiratory artefacts. Optimal position of the image reconstruction window relative to the cardiac cycle is significantly influenced by the heart rate during scanning. Diastolic reconstruction phases often allowed an optimal assessment in group A. Reconstruction phases from 30% to 45% are advisable for higher heart rates.


Abnormal epithelial cells recovered by bronchoalveolar lavage: are they malignant?
The recovery of neoplastic cells by bronchoalveolar lavage is useful in the diagnosis of lung cancer. Abnormal epithelial cells can also be recovered from patients with interstitial lung diseases who do not have cancer, and therefore the usefulness of lavage in the diagnosis of malignancy in this setting is unknown. In this study, we evaluated the diagnostic significance of abnormal lavage cells recovered from patients with diffuse parenchymal abnormalities and compared the usefulness of standard cytologic assessment, correlation with clinical features, and immunocytochemical staining for carcinoembryonic antigen (CEA) in identifying abnormal cells that are truly malignant. Thirty of 2,314 patients had atypical lavage cells, but in only nine was lung cancer demonstrated. Although most patients with clinical suspicion of malignancy had lung carcinoma (six of seven), one such patient did not have cancer, and three were shown to have unsuspected carcinoma. Cytologic criteria identified definitely malignant cells in only four of nine patients with lung cancer, indicating that the approach is not sensitive. Immunostaining of abnormal cells with anti-CEA antibodies proved helpful. All patients with lung malignancy had CEA+ cells (n = 9), and no patient whose abnormal cells were CEA- proved to have cancer (n = 17). Because only nine of 13 patients with CEA+ cells had lung malignancy, the test is not diagnostic, but it appears to limit the need for further evaluation to a smaller group of patients in whom cancer is likely to be present. When used together, cytopathologic findings, detection of CEA by immunocytochemical techniques, and clinical correlates proved useful in diagnosis of lung malignancy, but further improvements are still needed to improve diagnostic accuracy.


Genetic architecture of threshold reaction norms for male alternative reproductive tactics in Atlantic salmon (Salmo salar L.).
Alternative mating tactics have important ecological and evolutionary implications and are determined by complex interactions between environmental and genetic factors. Here, we study the genetic effect and architecture of the variability in reproductive tactics among Atlantic salmon males which can either mature sexually early in life in freshwater or more commonly only after completing a migration at sea. We applied the latent environmental threshold model (LETM), which provides a conceptual framework linking individual status to a threshold controlling the decision to develop alternative traits, in an innovative experimental design using a semi-natural river which allowed for ecologically relevant phenotypic expression. Early male parr maturation rates varied greatly across families (10 to 93%) which translated into 90% [64-100%] of the phenotypic variation explained by genetic variation. Three significant QTLs were found for the maturation status, however only one collocated with a highly significant QTL explaining 20.6% of the variability of the maturation threshold located on chromosome 25 and encompassing a locus previously shown to be linked to sea age at maturity in anadromous Atlantic salmon. These results provide new empirical illustration of the relevance of the LETM for a better understanding of alternative mating tactics evolution in natural populations.


Reduced incidence of hyperuricemia, gout, and renal failure following liver transplantation in comparison to heart transplantation: a long-term follow-up study.
Hyperuricemia and gout are common complications of heart transplantation, reaching a prevalence of 84% and 30%, respectively, in heart transplant recipients. In contrast, they are seldom reported following orthotopic liver transplantation (OLT). We retrospectively evaluated 75 consecutive liver transplant recipients and 47 consecutive heart transplant recipients, followed for at least 3 years after transplantation in a single transplantation center in Jerusalem, Israel. Data was collected on demographic and clinical variables, levels of uric acid, the occurrence of gout, renal function, and variables effecting hyperuricemia, such as weight and medications. Clinical gout was significantly more prevalent in heart recipients than in liver recipients (25.5% and 2.6%, respectively). Hyperuricemia was present in 100% of heart recipients, with an average uric acid level of 451 micromol/l, as compared with 85.7% and 403 micromol/l for liver recipients (P < 0.001 for both variables). Univariate analysis identified several parameters which significantly influenced the difference in hyperuricemia and gout among the two groups including age, gender, rejection episodes, hypertension, diabetes mellitus, the level of uric acid prior to transplantation, and the use of cyclosporine A, diuretics, steroids, and aspirin. Use of tacrolimus and azathioprine were associated with decreased incidence of hyperuricemia and gout. Multivariate analysis identified the type of transplantation as the only independent risk factor predicting the development of hyperuricemia and gout. Clinical gout and hyperuricemia were significantly more prevalent in heart recipients than in liver recipients. The disparity can be explained by differences in age, gender and renal function among the groups, as well as by the use of different medication regimens.


Psoriasis: evolving treatment for a complex disease.
The cutaneous manifestations of psoriasis can vary in morphology and severity, and therapy should be tailored accordingly. Biologic agents are important new options for treating patients with the most severe forms of the disease. All physicians should be aware that severe psoriasis may increase cardiovascular morbidity and the risk of death, and preventive strategies for patients with severe disease should be considered.


[Varicella-pox virus infection: features of the course, clinical manifestations, complications, and possibilities for prevention].
Varicella zoster virus (VZV) is a pathogenic human herpes virus that causes chickenpox as a primary infection, after which it persists for a long time and latently in the peripheral ganglia. Decades later, the virus can reactivate spontaneously, or after exposure to a number of triggering factors, causing herpes zoster (shingles). The reasons for the long-term persistence of VZV are gradually being revealed, but some issues remain unknown at the moment. Chickenpox and its complications are especially difficult in immunocompromised patients, but they are often found in people without risk factors. The most frequent and important complication of VZV reactivation is postherpetic neuralgia; encephalitis, segmental motor weakness and myelopathy, cranial neuropathies, and gastrointestinal complications often develop. The only scientifically proven effective and affordable way of mass prevention at the moment is vaccination. Chickenpox vaccines are safe and effective in preventing morbidity and mortality associated with the disease.


Intracellular Mono-ADP-Ribosylation in Signaling and Disease.
A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD⁺)-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases.


[Cyclodiathermy: is it effective in the treatment of glaucoma?].
The authors describe the non penetrating technique of cyclodiathermy in the treatment of different types of glaucoma and publish the results and the complications of the application of this technique on thirty three eyes among their patients. These eyes included congenital glaucoma (8 eyes), aphakic glaucoma (5 eyes), after silicone surgery (5 eyes), neovascular glaucoma (4 eyes), traumatic glaucoma (4 eyes), secondary glaucoma (3 eyes), Sturge-Weber-Krabbe (2 eyes) and open angle glaucoma (2 eyes). Their study with a mean follow up of 2.5 years shows an overall success rate of 60%. The success is defined as an ocular tension less than or equal to 22 mmHg in the absence of serious complications. All the encountered complications are mentioned. Phtysis occurred in not more than 3% of cases (1 eye). They establish a comparison with the published results and complications of the other cyclodestructive procedures: Sonocare, transcleral laser Yag, transcleral laser Ruby and cyclocryotherapy. This comparison does not prove the superiority of these other procedures with regard to the non penetrating cyclodiathermy. They conclude that this non penetrating cyclodiathermy is a non expensive procedure which still have its good therapeutic value.


Endodontic treatment of a non-vital permanent tooth with an open root apex using mineral trioxide aggregate.
A 2-year-old domestic feline patient was presented for evaluation of a complicated crown fracture of the right maxillary canine tooth. Clinical and radiographic examination revealed a non-vital immature permanent canine tooth with an open apex. This case report describes a two-visit technique using mineral trioxide aggregate in an apical barrier method for the treatment of a non-vital immature permanent canine tooth in a cat.


Relative importance measures for reprioritization response shift.
Response shift (RS), a change in the meaning of an individual's self-evaluation of a target construct, such as health-related quality of life (HRQOL), can affect the interpretation of change in measures of the construct collected over time. This study proposes new statistical methods to test for reprioritization RS, in which the relative importance of HRQOL domains changes over time. The methods use descriptive discriminant analysis or logistic regression models and bootstrap inference to test for change in relative importance weights (method 1) or ranks (method 2) for discriminating between patient groups at two occasions. The methods are demonstrated using data from the Manitoba Inflammatory Bowel Disease (IBD) Cohort Study (n = 388). Reprioritization of domains from the IBD Questionnaire (IBDQ) and SF-36 was investigated for groups with active and inactive disease symptoms. The IBDQ bowel symptoms and SF-36 bodily pain domains had the highest ranks for group discrimination. Using Method 1, there was evidence of reprioritization RS in the IBDQ social functioning domain and the SF-36 bodily pain and social functioning domains. Method 2 did not detect change for any of the domains. Compared to IBD patients without active disease symptoms, those with active symptoms were likely to change the meaning of their self-evaluations of pain and social interactions. Further research is needed to compare these new RS detection methods under a variety of data analytic conditions before recommendations about the optimal method can be made.


Allergic rhinitis. Recognizing signs, symptoms, and triggering allergens.
Runny noses, sneezing, nasal congestion, and other nuisance symptoms are part and parcel of primary care practice. But how can you quickly discern which symptoms are related to common colds and which stem from allergic rhinitis? Careful history taking usually provides clues, but allergy testing may be needed when triggers are not clear. In this first of two articles on allergic rhinitis, Dr Ferguson explains what to look for, what questions to ask, when to test for allergies, and how to modify a patient's environment to minimize problems. The second article, beginning on page 117, discusses pharmacologic treatment and immunotherapy for allergic rhinitis.


New storage procedure for human tumor biopsies prior to estrogen receptor measurement.
Breast tumor biopsies required for steroid receptor determination are normally frozen in liquid nitrogen and stored until assay. However, some limitations of this type of storage exist. To try to both eliminate the need for liquid nitrogen and as part of a study of serial assays on a single tumor biopsy, alternative storage media were investigated. This study shows that storage of breast tumor biopsies at -20 degrees in sucrose buffer made 50% in glycerol prevented the tissues from freezing, yet retained the specific estrogen receptor content both quantitatively and in terms of molecular form (8S:4S ratio). Receptor was stable for up to 100 days, and individual samples could be successfully reassayed throughout this period. Forty-four biopsies from 40 patients were halved, and one section from each was stored in liquid nitrogen, while the other was stored in sucrose:glycerol. Overall, the correlation of receptor content between the two storage methods was good. Using a clinical cutoff value of 20 fmol/mg cytosol protein, only one sample of the 44 would have been classified differently after storage in the two media. Progesterone receptor in biopsies stored in sucrose:glycerol also appears to be stable for at least a limited period.


Maxillofacial trauma: current practice in management at Pakistan Institute of Medical Sciences.
This study was carried out to determine the aetiology, pattern and management of maxillofacial injuries at PIMS, Islamabad. This descriptive study was conducted at Plastic Surgery Department, PIMS Islamabad from 1st February 1998 to 30th April 2002. All the adult patients presenting with maxillofacial injures were included where as patients less than 12 years of age and only facial lacerations were excluded. Similarly isolated nasal bone fractures were also excluded because these patients were routinely managed by ENT department. Age, sex, presentation, aetiology, associated injuries and treatment modalities undertaken in these patients were recorded. In 164 patients 254 fractures were noted. Most were male (86%), ranging in age from 13-71 years with a male to female ratio of 6:1 respectively. The most frequent (48%) cause noticed was road traffic accidents followed by assault. Mandible was the commonest to be involved in such injuries followed by maxilla. Most of the patients (32%) had associated facial injuries. Various treatment modalities were practiced. Maxillofacial fractures should be managed by open reduction and internal fixation as early as possible.


Development of SCAR markers and UP-PCR cross-hybridization method for specific detection of four major subgroups of Rhizoctonia from infected turfgrasses.
A rapid identification assay for Waitea circinata (anamorph: Rhizoctonia spp.) varieties zeae and circinata causing patch diseases on turfgrasses was developed based on the universally primed PCR (UP-PCR) products cross-blot hybridization. Tester isolates belonging to the two varieties of W. circinata were amplified with a single UP primer L21, which generated multiple DNA fragments for each variety. Probes were prepared with UP-PCR products of each tester isolate by labeling with digoxigenin. Fieldcollected W. circinata isolates and representative isolates of different R. solani anastomosis groups (AG) and AG subgroups were amplified with L21, immobilized on nylon membrane and cross hybridized with the two probes. Isolates within a W. circinata variety cross-hybridized strongly, while non-homologous isolates did not cross-hybridize or did so weakly. Closely related W. circinata varieties zeae and circinata were clearly distinguished with this assay. Sequence-characterized amplified region (SCAR) markers also were developed from UP-PCR products to identify isolates of Thanatephorus cucumeris (anamorph: R. solani) AG 1-IB and AG 2-2IIIB. These two AGs are commonly isolated from diseased, cool-season turfgrasses. The specific SCAR markers that were developed could differentiate isolates of AG 1-IB or AG 2-2IIIB groups. These SCAR markers did not amplify a product from genomic DNA of nontarget isolates of Rhizoctonia. The specificities and sensitivities of the SCAR primers were tested on total DNA extracted from several field-grown, cool-season turf species having severe brown-patch symptoms. First, the leaf samples from diseased turf species were tested for the anastomosis groups of the causal pathogen, and thereafter the total DNA was amplified with the specific primers. The specific primers were sensitive and unique enough to produce a band from total DNA of diseased turfgrasses infected with either AG 1-IB or AG 2-2IIIB.


Relationship between plasma vitamin C and serum diagnostic biochemical markers in lactating cows.
We investigated the relationship between plasma vitamin C concentration and serum levels of some diagnostic biochemical markers in 118 lactating Holstein cows. Blood sample was collected once from each cow and we measured the plasma vitamin C concentration and the serum levels of glucose, beta-hydroxybutyrate, free fatty acids, triacylglycerol, total cholesterol, albumin, total bilirubin, alkaline phosphatase, aspartate aminotransferase and gamma-glutamyltransferase. The regression of plasma vitamin C with each serum diagnostic biochemical marker indicated that the vitamin C concentration significantly decreased as glucose, alkaline phosphatase or aspartate aminotransferase level increased and as total cholesterol or albumin concentration decreased. Furthermore, the plasma vitamin C concentration was significantly lower in the cows showing that each of these marker levels was out of its reference interval than in the cows showing that the marker level was within its reference interval. The significant correlations were observed among total cholesterol, albumin, alkaline phosphatase and aspartate aminotransferase levels, to which the glucose concentration was not related. These results showed that the plasma vitamin C concentration was low in the cows that had concurrently low levels of total cholesterol and albumin, and high levels of alkaline phosphatase and aspartate aminotransferase. Therefore, a hepatic malfunction possibly decreases plasma vitamin C concentration through suppressing vitamin C production. On the other hand, the high level of glucose possibly decreases plasma vitamin C concentration through suppressing vitamin C recycling.


Hospital library service and the changes in national standards.
Two important sets of standards affecting hospital libraries were significantly revised in 1994, those of the Medical Library Association (MLA) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). As part of its continuing efforts to monitor library services within its region, the University of California, Los Angeles Biomedical Library, Regional Medical Library for the Pacific Southwest Region of the National Network of Libraries of Medicine (NN/LM) conducted a survey in late 1994, in part to determine the effects of these revised standards on regional hospital libraries. Data from the survey were also used to provide a view of hospital libraries in the Pacific Southwest region, and to make comparisons with similar data collected in 1989. Results showed that while libraries remained stable in overall number, size, and staffing, services, especially those associated with end-user searching and interlibrary loan, increased enormously. With respect to the MLA standards, results show a high compliance level. Interesting differences were seen between the perceptions of library staff concerning their rate of compliance with the JCAHO standards and their actual compliance as measured by the MLA criteria. While some libraries appear to measure up better than their own perceptions would indicate, others may be fully aware of their actual compliance level.


Pre-cooling with intermittent ice ingestion lowers the core temperature in a hot environment as compared with the ingestion of a single bolus.
The timing in which ice is ingested may be important for optimizing its success. However, the effects of differences in the timing of ice ingestion has not been studied in resting participants. Therefore, the purpose of this study was to investigate the effects of differences in the timing of ice ingestion on rectal temperature (Tre) and rating of perceptual sensation in a hot environment. Seven males ingested 1.25gkg(-1) of crushed ice (ICE1.25: 0.5°C) or cold water (CON: 4°C) every 5min for 30min, or were given 7.5gkgBM(-1) of crushed ice (ICE7.5) to consume for 30min in a hot environment (35°C, 30% relative humidity). The participants then remained at rest for 1h. As physiological indices, Tre, body mass and urine specific gravity were measured. Rating of thermal sensation was measured at 5-min intervals throughout the experiment. ICE1.25 continued to decrease Tre until approximately 50min, and resulted in a greater reduction in Tre (-0.56±0.20°C) than ICE7.5 (-0.41±0.14°C). Tre was reduced from 40 to 75min by ICE1.25, which is a significant reduction in comparison to ICE7.5 (p<.05). Mean RTS with ICE1.25 at 50-65min was significantly lower than that with ICE7.5 (p<.05). These results suggest that pre-cooling with intermittent ice ingestion is a more effective strategy both for lowering the Tre and for the rating of thermal sensation.


Cholangiocarcinoma in choledochal cyst after cystoenterostomy: how a mistreated choledochal cyst can progress to malignancy.
This case report presents an unusual case of cholangiocarcinoma arising nearly 35 years after cystoduodenostomy for choledochal cyst. The patient visited our hospital with dyspepsia and studies revealed bezoar within the choledochal cyst caused by bile and food reflux. The patient underwent pancreaticoduodenectomy and a biopsy revealed adenocarcinoma, stage IIB. After 19 months, the patient has no recurrence to date and has recovered well. This case shows that proper surgical management and meticulous, long-term follow-up is imperative for patients with congenital choledochal cyst.


How the brain handles temporally uncoupled bimanual movements.
Whereas the cerebral representation of bimanual spatial coordination has been subject to prior research, the networks mediating bimanual temporal coordination are still unclear. The present study used functional imaging to investigate cerebral networks mediating temporally uncoupled bimanual finger movements. Three bimanual tasks were designed for the execution of movements with different timing and amplitude, with same timing but different amplitude, and with same timing and amplitude. Functional magnetic resonance imaging results showed an increase of activation within right premotor and dorsolateral prefrontal, bilateral inferior parietal, basal ganglia, and cerebellum areas related to temporally uncoupled bilateral finger movements. Further analyses showed a decrease of connectivity between homologous primary hand motor regions. In contrast, there was an increase of connectivity between motor regions and anterior cingulate, premotor and posterior parietal regions during bimanual movements that were spatially or both temporally and spatially uncoupled, compared with bimanual movements that were both spatially and temporally coupled. These results demonstrate that the extent of bihemispheric coupling of M1 areas is related to the degree of temporal synchronization of bimanual finger movements. Furthermore, inferior parietal and premotor regions play a key role for the implementation not only of spatial but also of temporal movement parameters in bimanual coordination.


A prospective study of total plasma cell-free DNA as a predictive biomarker for response to systemic therapy in patients with advanced non-small-cell lung cancers.
While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for systemic therapy response. We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6-12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal-Wallis and Kaplan-Meier estimates. A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93-1.20, P = 0.41] or OS (HR = 1.04, 95% CI 0.93-1.17, P = 0.51), neither were changes in cfDNA. In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing.


Nursing priorities in caring for patients with intracerebral hemorrhage.
Patients afflicted with intracerebral hemorrhage (ICH) experience potentially devastating neurological sequelae; current therapy for ICH remains supportive. However, hemostatic therapy with recombinant activated factor VIIa holds promise for decreasing the morbidity and mortality of patients following an ICH. Nurses who are the responsible clinicians at the bedside often find it challenging to care for these patients. This article discusses the priorities that nurses need to determine as they balance the overall needs of the patient, incorporating recombinant activated factor VIIa as a new treatment for ICH.


Effect of swimming training on antioxidant enzymes in kidney of young and old mice.
The current study was undertaken to investigate the effect of swimming training on the antioxidant enzyme system in kidney of young and old mice. Both young and old mice, aged 2 and 26 months old, respectively, were divided into the sedentary and swimming-trained groups. The trained mice underwent a 6-week swimming program (1 h/day, 5 days/week) in water at 35-36 degrees C. Cu,Zn-superoxide dismutase (Cu,Zn-SOD) activity was significantly decreased with aging but was not influenced by swimming training, such changes being similar to those noted for catalase activity rather than for glutathione peroxidase activity. After swimming training Mn-SOD activity increased significantly only in old mice but was unaffected by aging. Although neither aging nor swimming training had overt effect on the expression of Cu,Zn-SOD mRNA, the immunoreactive Cu,Zn-SOD content in young mice decreased significantly after the training. Meanwhile, Mn-SOD mRNA expression in old mice was reduced by half after swimming training, accompanied by a significant decrease in its immunoreactive content; unexpectedly, however, Mn-SOD content in young mice did not parallel its mRNA expression. These findings suggest that the antioxidant enzyme system in mouse kidney trends to be down-regulated with aging, and that swimming training fails to attenuate such reduced levels of the antioxidant enzymes.


Malignant biliary obstruction: complications of percutaneous biliary drainage.
The medical records of 161 patients who underwent percutaneous biliary drainage (PBD) for malignant biliary obstruction were reviewed with attention to the complications resulting from this mode of drainage. Observed was a higher incidence of complications--particularly of cholangitis--than that generally reported in the literature. Although PBD is an effective method of biliary drainage, it carries a high risk of cholangitis in patients with cancer, who frequently receive myelosuppressive agents that predispose them to infections.


The covert symphony: cellular and molecular accomplices in breast cancer metastasis.
Breast cancer has emerged as the most commonly diagnosed cancer and primary cause of cancer-related deaths among women worldwide. Although significant progress has been made in targeting the primary tumor, the effectiveness of systemic treatments to prevent metastasis remains limited. Metastatic disease continues to be the predominant factor leading to fatality in the majority of breast cancer patients. The existence of a prolonged latency period between initial treatment and eventual recurrence in certain patients indicates that tumors can both adapt to and interact with the systemic environment of the host, facilitating and sustaining the progression of the disease. In order to identify potential therapeutic interventions for metastasis, it will be crucial to gain a comprehensive framework surrounding the mechanisms driving the growth, survival, and spread of tumor cells, as well as their interaction with supporting cells of the microenvironment. This review aims to consolidate recent discoveries concerning critical aspects of breast cancer metastasis, encompassing the intricate network of cells, molecules, and physical factors that contribute to metastasis, as well as the molecular mechanisms governing cancer dormancy.