Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression.
Acute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population. We conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay. A total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81-201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97-267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714-0.853). NGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.


Proximate nutrient analyses of four species of submerged aquatic vegetation consumed by Florida manatee (Trichechus manatus latirostris) compared to romaine lettuce (Lactuca sativa var. longifolia).
Free-ranging Florida manatees (Trichechus manatus latirostris) consume a variety of sea grasses and algae. This study compared the dry matter (DM) content, proximate nutrients (crude protein [CP], ether-extracted crude fat [EE], nonfiber carbohydrate [NFC], and ash), and the calculated digestible energy (DE) of sea grasses (Thalassia testudinum, Halodule wrightii, and Syringodium filiforme) collected in spring, summer, and winter, and an alga (Chara sp.) with those of romaine lettuce (Lactuca sativa var. longifolia). Neutral-detergent fiber (NDF), acid-detergent fiber (ADF), and lignin (L) measured after ash-extraction were also compared. Results of statistical tests (C = 0.01) revealed DM content was higher in aquatic vegetation than in lettuce (P = 0.0001), but NDF and ADF were up to threefold greater, EE (P = 0.00001) and CP (P = 0.00001) were 2-9 times less, and NFC (P = 0.0001) was 2-6 times lower in sea grass than in lettuce, on a DM basis. Chara was lower in NDF, ADF, L, EE, CP, and NFC relative to lettuce on a DM basis. Ash content (DM basis) was higher (P = 0.0001), and DE was 2-6 times lower in aquatic vegetation than in lettuce. Sea grass rhizomes had lower L and higher ash contents (DM basis) than sea grass leaves. Based on the nutrient analyses, romaine lettuce and sea grasses are not equivalent forages, which suggests that the current diet of captive Florida manatees should be reassessed.


Learning to perceive pitch differences.
This paper reports two experiments concerning the stimulus specificity of pitch discrimination learning. In experiment 1, listeners were initially trained, during ten sessions (about 11,000 trials), to discriminate a monaural pure tone of 3000 Hz from ipsilateral pure tones with slightly different frequencies. The resulting perceptual learning (improvement in discrimination thresholds) appeared to be frequency-specific since, in subsequent sessions, new learning was observed when the 3000-Hz standard tone was replaced by a standard tone of 1200 Hz, or 6500 Hz. By contrast, a subsequent presentation of the initial tones to the contralateral ear showed that the initial learning was not, or was only weakly, ear-specific. In experiment 2, training in pitch discrimination was initially provided using complex tones that consisted of harmonics 3-7 of a missing fundamental (near 100 Hz for some listeners, 500 Hz for others). Subsequently, the standard complex was replaced by a standard pure tone with a frequency which could be either equal to the standard complex's missing fundamental or remote from it. In the former case, the two standard stimuli were matched in pitch. However, this perceptual relationship did not appear to favor the transfer of learning. Therefore, the results indicated that pitch discrimination learning is, at least to some extent, timbre-specific, and cannot be viewed as a reduction of an internal noise which would affect directly the output of a neural device extracting pitch from both pure tones and complex tones including low-rank harmonics.


Knowledge, attitude, and practice of Indonesian farmers regarding the use of personal protective equipment against pesticide exposure.
The use of synthetic pesticides in tropical countries has increased over the years, following the intensification of agriculture. However, awareness among farmers of the importance of protecting themselves from hazards associated with pesticide application is still lacking, especially in Indonesia. This paper reports results of an inventory on knowledge and attitudes regarding pesticide use by melon farmers of a village in Central Java, Indonesia. The importance of using personal protective equipment such as hats, masks, goggles, boots, and gloves on agricultural land is known and well understood by the farmers. However, in practice, only 3.8 % were wearing glasses and 1.9 % were using boots. In fact, the masks used only consisted of a part of their shirt tied around the mouth. The farmers were not wearing long pants and shirts with long sleeves and used the same clothes for more than 1 day without washing. Almost no farmers used personal protective equipment that was standard, in good condition, and complete. Based on the results of statistical analysis, no significant relationship was found between knowledge and attitude on the required practices on the one hand and the use of personal protective equipment in practice on the other hand. This shows that improved knowledge and attitudes are not enough to change the behavior of farmers to work in a healthy and safe way. The gap between knowledge and practice needs to be bridged by a more interactive and participatory training model. It is therefore of paramount importance to develop a special toolkit for pesticide risk reduction which is developed in a participatory manner involving the farmers as the main actors through a series of focus group discussions and field simulations.


Weight-Related Perceptions and Experiences of Young Adult Women in Southwest Georgia.
Young adulthood is a period of pronounced weight gain, though few weight management interventions exist for this population. This qualitative study explored how young adult women feel about their weight, what kinds of weight-related advice they have received, and concerns about future weight gain to inform the adaptation of a weight gain prevention intervention. Forty women completed semistructured, in-depth interviews, which were digitally recorded, transcribed verbatim, coded, and analyzed using thematic analysis. Participants were women aged 20 to 29 years, primarily overweight (12.5%) or obese (55.0%), and African American (65.0%). Participants expressed dissatisfaction with their current weight and reported receiving advice to lose weight from multiple sources. Direct, health-focused advice from health care professionals tended to be received more positively than indirect, appearance-focused advice from family members and romantic partners. Participants expressed concern about future weight gain, either as a result of a family history of obesity or chronic disease, pregnancy, and child-rearing, or unhealthy lifestyle patterns. Future weight gain was anticipated to impact chronic disease risk, changes in physical appearance, and interference with daily activities. Results suggest that young adult women may be receptive to participating in weight management interventions and that health care systems may be strategic implementation partners.


Determinants of aerosol lung-deposited surface area variation in an urban environment.
Ultrafine particles are characterized by a high surface area per mass. Particle surface has been reported to play a significant role in determining the toxicological activity of ultrafine particles. In light of this potential role, the time variation of lung deposited surface area (LDSA) concentrations in the alveolar region was studied at the urban background environment of Barcelona (Spain), aiming to asses which processes and sources govern this parameter. Simultaneous data on Black Carbon (BC), total particle number (N) and particle number size distribution were correlated with LDSA. Average LDSA concentrations in Barcelona were 37 ± 26 μm(2)cm(-3), levels which seem to be characteristic for urban environments under traffic influence across Europe. Results confirm the comparability between LDSA data provided by the online monitor and those calculated based on particle size distributions (by SMPS), and reveal that LDSA concentrations are mainly influenced by particles in the size range 50-200 nm. A set of representative daily cycles for LDSA concentrations was obtained by means of a k-means cluster technique. The contribution of traffic emissions to daily patterns was evidenced in all the clusters, but was quantitatively different. Traffic events under stable atmospheric conditions increased mean hourly background LDSA concentrations up to 6 times, attaining levels higher than 200 μm(2)cm(-3). However, under warm and relatively clean atmospheric conditions, the traffic rush hour contribution to the daily LDSA mean appeared to be lower and the contribution of new urban particle formation events (by photochemically induced nucleation) was detected. These nucleation events were calculated to increase average background LDSA concentrations by 15-35% (maximum LDSA levels=45-50 μm(2)cm(-3)). Thereby, it may be concluded that in the urban background of Barcelona road traffic is the main source increasing the aerosol surface area which can deposit on critical regions of the human lung, followed by nucleation episodes.


The Role of LORELEI in Pollen Tube Reception at the Interface of the Synergid Cell and Pollen Tube Requires the Modified Eight-Cysteine Motif and the Receptor-Like Kinase FERONIA.
In angiosperms, pollen tube reception by the female gametophyte is required for sperm release and double fertilization. In Arabidopsis thaliana lorelei (lre) mutants, pollen tube reception fails in most female gametophytes, which thus remain unfertilized. LRE encodes a putative glycosylphosphatidylinositol (GPI)-anchored surface protein with a modified eight-cysteine motif (M8CM). LRE fused to citrine yellow fluorescent protein (LRE-cYFP) remains functional and localizes to the synergid plasma membrane-rich filiform apparatus, the first point of contact between the pollen tube and the female gametophyte. Structure-function analysis using LRE-cYFP showed that the role of LRE in pollen tube reception requires the M8CM, but not the domains required for GPI anchor addition. Consistently, LRE-cYFP-TM, where GPI anchor addition domains were replaced with a single-pass transmembrane domain, fully complemented the pollen tube reception defect in lre-7 female gametophytes. Ectopically expressed and delivered LRE-cYFP from pollen tubes could non-cell-autonomously complement the pollen tube reception defect in lre female gametophytes, only if they expressed FERONIA. Additionally, pollen tube-expressing LRE variants lacking domains critical for GPI anchor addition also rescued lre female gametophyte function. Therefore, LRE and FERONIA jointly function in pollen tube reception at the interface of the synergid cell and pollen tube.


Simultaneous determination of ten amphetamine designer drugs in human whole blood by capillary electrophoresis with diode array detection.
In recent years, a number of new designer drugs have entered the illicit drug market. The methylenedioxyderivatives of amphetamine represent the largest group of designer drugs. This paper describes a method for screening for and simultaneously quantifying 10 2,5-methylenedioxy-derivatives of amphetamine and phenethylamine in human whole blood, using capillary electrophoresis (CE) with diode array detection (DAD). Using an aqueous pH 2.5 phosphate buffer, CE analysis gave peaks with good symmetry and reproducible migration times. Under these experimental conditions, the 10 amphetamines were resolved in 15 min and without interference from biological matrices (blood). Their identification by migration time was confirmed by their UV spectra recorded with a DAD (190-350 nm). The main advantages of the present method lie in its simplicity, clean and reliable extraction from human whole blood and simultaneous detection and quantification by CE-DAD. The applicability of the method was demonstrated by analysis of in vivo rat blood samples. The method was validated according to international guidelines.


Brain "ouabain" and angiotensin II contribute to cardiac dysfunction after myocardial infarction.
In chronic heart failure (CHF), sympathetic activity increases in parallel with the impairment of left ventricle (LV) function, and sympathetic hyperactivity has been postulated to contribute to the progression of heart failure. In the brain, compounds with ouabain-like activity ("ouabain," for brevity) and the renin-angiotensin system contribute to sympathetic hyperactivity in rats with CHF after myocardial infarction (MI). In the present studies, we assessed whether, in rats, chronic blockade of brain "ouabain" or the brain renin-angiotensin system inhibits the post-MI LV dysfunction. In rats, an MI was induced by acute coronary artery ligation. At either 0.5 or 4 wk post-MI, chronic treatment with Fab fragments for blocking brain "ouabain" or with losartan for blocking brain AT(1) receptors was started and continued until 8 wk post-MI using osmotic minipumps connected to intracerebroventricular cannulas. At 8 wk post-MI, in conscious rats, LV pressures were measured at rest and in response to volume and pressure overload, followed by LV passive pressure-volume curves in vitro. At 8 wk post-MI, control MI rats exhibited clear increases in LV end-diastolic pressure (LVEDP) at rest and in response to pressure and volume overload. LV pressure-volume curves in vitro showed a marked shift to the right. Intravenous administration of the Fab fragments or losartan at rates used for central blockade did not affect these parameters. In contrast, chronic central blockade with either Fab fragments or losartan significantly lowered LVEDP at rest (only in 0.5- to 8-wk groups) and particularly in response to pressure or volume overload. LV dilation, as assessed from LV pressure-volume curves, was also significantly inhibited. These results indicate that chronic blockade of brain "ouabain" or brain AT(1) receptors substantially inhibits development of LV dilation and dysfunction in rats post-MI.


[Structural changes in spinal cord gray matter induced by gravitational overloads].
After acute exposure of rats to gravitational overloads (GO) the reactive changes in neurons and interneuronal synapses of spinal cord were found. These are interpreted as morphologic signs of increased functional activity of neurons and activation of interneuronal impulse transmission. Chronic application of GO results in both reactive changes and damage of spinal cord structures. These changes were not seen after an acute exposure to GO, and thus they are associated with the repeated GO, indicating GO cumulative effect. Administration of "Vitavis" provides a membrane-protective effect, especially in respect to mitochondria of neurons and perineuronal glial cells in cervical and thoracic segments of spinal cord. The effect was less pronounced in spinal cord lumbar segments as a result of pericapillary edema, preventing the transport or drug from capillary bed to the neural structures.


Asian Americans have greater prevalence of metabolic syndrome despite lower body mass index.
To examine the relationship between body mass index (BMI) and metabolic syndrome for Asian Americans and non-Hispanic Whites (NHWs), given that existing evidence shows racial/ethnic heterogeneity exists in how BMI predicts metabolic syndrome. Electronic health records of 43,507 primary care patients aged 35 years and older with self-identified race/ethnicity of interest (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese or NHW) were analyzed in a mixed-payer, outpatient-focused health-care organization in the San Francisco Bay Area. Metabolic syndrome prevalence is significantly higher in Asians compared with NHWs for every BMI category. For women at the mean age of 55 and BMI of 25 kg m(-2), the predicted prevalence of metabolic syndrome is 12% for NHW women compared with 30% for Asians; similarly for men, the predicted prevalence of metabolic syndrome is 22% for NHWs compared with 43% of Asians. Compared with NHW women and men with a BMI of 25 kg m(-2), comparable prevalence of metabolic syndrome was observed at BMI of 19.6 kg m(-2) for Asian women and 19.9 kg m(-2) for Asian men. A similar pattern was observed in disaggregated Asian subgroups. In spite of the lower BMI values and lower prevalence of overweight/obesity than NHWs, Asian Americans have higher rates of metabolic syndrome over the range of BMI. Our results indicate that BMI ranges for defining overweight/obesity in Asian populations should be lower than for NHWs.


Continuing Mycobacterium bovis transmission from animals to humans in New Zealand.
New Zealand has a large reservoir of Mycobacterium bovis infection in wild and farmed animals. This study aimed to assess the extent of human infection with this organism and the potential contribution of these animal sources. Combined epidemiological and laboratory investigation of human tuberculosis cases over the period 1995-2002 showed that M. bovis accounted for 2.7% (54/1997) of laboratory-confirmed human tuberculosis cases, a rate of 0.2/100,000 population. M. bovis isolates from humans (23) were typed using restriction endonuclease analysis (REA) and compared with isolates from wild and domestic animals (2600). Fourteen (61%) of the human isolates had REA patterns that were identical to patterns for isolates from cattle, deer, possums, ferrets, pigs, and occasionally cats. These results suggest a low level of ongoing M. bovis transmission from animal reservoirs to humans in New Zealand.


Influence of pulse energy, tip design and insertion depth during Er:YAG-activated irrigation on cleaning efficacy in simulated severely curved complex root canal systems in vitro.
To investigate the influence of pulse energy, tip geometry and tip position in simulated 3D-printed root canals with multiple side canals at different levels in all directions on the cleaning performance of laser-activated irrigation (LAI) compared to sonic activation (EDDY) and conventional needle irrigation (NI). 3D-printed root canal models (25/.06, length 20 mm, curvature 60°, radius 5 mm) with side canals (diameter 0.2 mm) at 2, 5 and 8 mm from the apex were filled with coloured biofilm-mimicking hydrogel. LAI (Morita AdvErL Evo, Kyoto, Japan) was performed with six settings (n = 20; pulse-energy, pulses per second [PPS], tip position): LAI1 (50 mJ, 25 PPS, P400FL, canal entrance [CE]), LAI2 (same as LAI1, but insertion depth 9 mm before the apical endpoint [AE] [corresponding to 1 mm above the first lateral canals]), LAI3 (80 mJ, 25 PPS, P400FL, 9 mm before AE), LAI4 (same as LAI 3, but at CE) for 3 × 20 s each, LAI5 (50 mJ, 25 PPS, P400FL 2 × 20 s, CE & R200T (30 mJ, 25 PPS, 1 × 20 s, 9 mm before AE), LAI6 (30 mJ, 25 PPS, R200T, 9 mm before AE, 3 × 20 s). A continuous irrigation (3 mL/20 s) using distilled water accompanied the irrigation cycles. NI and EDDY (3 × 20 s each; 3 mL/20 s irrigation, insertion AE minus 1 mm, amplitude 4 mm) served as control groups. Biofilm-mimicking hydrogel removal (ImageJ, NIH) was assessed for the entire system, the central canal and the lateral canals using standardized photographs with a microscope (Expert DN, Müller-Optronic) and statistically analysed was performed using Kruskal-Wallis and Dunn tests (p = .05). Irrigant extrusion beyond the foramina was also recorded. LAI2 (99.08%; interquartile range [IQR]: 96.85-100.00) and LAI3 (97.50%; 96.24-100.00) achieved the significantly best and LAI6 (80.08%; 73.41-84.69) the significantly worst removal of hydrogel from the entire root canal system amongst all LAI configurations (p < .05). There were no significant differences between LAI6, EDDY (72.89%; 67.49-76.22) and manual irrigation (54.39%; 51.01-56.94) (p > .05). R200T laser tip caused significantly more often irrigant extrusion than all other techniques (p < .05). Tip design, energy settings, and the positioning of the laser tip below the canal entrance caused an improvement in cleaning performance of the LAI. However, the small R200T tip created significantly more procedural errors (irrigant extrusion) due to higher concentrated energy.


Development of simple-to-apply biogas kinetic models for the co-digestion of food waste and maize husk.
Biogas kinetic models are often used to characterize substrate degradation and prediction of biogas production potential. Most of these existing models are however difficult to apply to substrates they were not developed for since their applications are usually substrate specific. Biodegradability kinetic (BIK) model and maximum biogas production potential and stability assessment (MBPPSA) model were therefore developed in this study for better understanding of the anaerobic co-digestion of food waste and maize husk for biogas production. Biodegradability constant (k) was estimated as 0.11 d(-1) using the BIK model. The results of maximum biogas production potential (A) obtained using the MBPPSA model were found to be in good correspondence, both in value and trend with the results obtained using the popular but complex modified Gompertz model for digesters B-1, B-2, B-3, B-4, and B-5. The (If) value of MBPPSA model also showed that digesters B-3, B-4, and B-5 were stable, while B-1 and B-2 were inhibited/unstable. Similar stability observation was also obtained using the modified Gompertz model. The MBPPSA model can therefore be used as an alternative model for anaerobic digestion feasibility studies and plant design.


Is there a unique nursing ethic?
There is no agreement in the nursing literature as to the meaning of the term, nursing ethics. Proposed definitions refer to nurses' moral decision-making and behaviors, ethical conflicts, and analysis of ethical issues that arise within nurses' practice. Presumably, a distinct nursing ethic should address unique theories, standards, and inquiry into what comprises nurses' ethical behavior and study of how nurses actually behave and reason about ethical issues. The purpose of this column is to synthesize the dialogue regarding the potential existence of a unique nursing ethic, and to propose that such an ethic has yet to emerge.


Transmission d'images en couleurs dans des fibres optiques par codage polychromatique.
Color image transmission through a 1-D array of 150 parallel multimode optical fibers is demonstrated using chromatic encoding of both geometric and spectral structures of self-luminous incoherent sources. The spectroscopic encoding and decoding devices include infrared type echelette gratings working at high diffraction orders in the range of the visible wavelengths considered in these experiments (~0.45-0.75, microm). Very good image and color quality was achieved: 2.5 x 10(4) pixels, seven spectral components per pixel.


[Nursing: organization, functions, and efficacy].
This article analyzes the defining traits of primary health care: length, accessibility, integrity, and coordination/continuity while bearing in mind the influence which these traits have on the organizational purpose of nursing. The evolution of nursing is also studied as it relates to the various reform phases in primary health care: the impulse phase and the implementation phase. A few aspects of this article were presented at the IV Primary Health Care Nursing Meeting which took place in Murcia.


Characterization of thermally stable Brønsted acid sites on alumina-supported niobium oxide after calcination at high temperatures.
Thermally stable Brønsted acid sites were generated on alumina-supported niobium oxide (Nb2O5/Al2O3) by calcination at high temperatures, such as 1123 K. The results of structural characterization by using Fourier-transform infrared (FTIR) spectroscopy, TEM, scanning transmission electron microscopy (STEM), and energy-dispersive X-ray (EDX) analysis indicated that the Nb2O5 monolayer domains were highly dispersed over alumina at low Nb2O5 loadings, such as 5 wt%, and no Brønsted acid sites were presents. The coverage of Nb2O5 monolayer domains over Al2O3 increased with increasing Nb2O5 loading and almost-full coverage was obtained at a loading of 16 wt%. A sharp increase in the number of hydroxy groups, which acted as Brønsted acid sites, was observed at this loading level. The relationship between the acidic properties and the structure of the material suggested that the bridging hydroxy groups (Nb-O(H)-Nb), which were formed at the boundaries between the domains of the Nb2O5 monolayer, acted as thermally stable Brønsted acid sites.


[Bone marrow transplantation and cord blood transplantation in children]
OBJECTIVE: To review the indications, main steps and complications of bone marrow transplantation in children. SOURCES: Medline-based literature review. SUMMARY OF THE FINDINGS: We comment about the indications of autologous, allogeneic and syngeneic bone marrow transplantation, donor selections, harvest and infusion of the hematopoietic progenitor cells that will reconstitute the hematopoietic and immune systems. We describe the different conditioning regimens and the new sources of cells, such as cord blood. We also describe the most common events after the procedure, including infections, graft versus host disease, and cardiovascular, pulmonary, hepatic, genitourinary, and gastrointestinal complications. The late effects and their impact on quality of life are also discussed. CONCLUSIONS: Bone marrow transplantation does not confer an absolutely normal life span to all the patients; however, it represents the only chance of cure for children with certain neoplastic or immunological diseases. By knowing the steps of the procedure, pediatricians can be a source of information on bone marrow transplantation to the patients and their families.


Mechanism of charged pollutants removal in an ion exchange membrane bioreactor: drinking water denitrification.
The mechanism of anionic pollutant removal in an ion exchange membrane bioreactor (IEMB) was studied for drinking water denitrification. This hybrid process combines continuous ion exchange transport (Donnan dialysis) of nitrate and its simultaneous bioreduction to gaseous nitrogen. A nonporous mono-anion permselective membrane precludes direct contact between the polluted water and the denitrifying culture and prevents secondary pollution of the treated water with dissolved nutrients and metabolic products. Complete denitrification may be achieved without accumulation of NO3(-) and NO2(-) ions in the biocompartment. Focus was given to the effect of the concentration of co-ions, counterions, and ethanol on the IEMB performance. The nitrate overall mass transfer coefficient in this hybrid process was found to be 2.8 times higher compared to that in a pure Donnan dialysis process without denitrification. Furthermore, by adjusting the ratio of co-ions between the biocompartment and the polluted water compartment, the magnitude and direction of each individual anion flux can be easily regulated, allowing for flexible process operation and control. Synthetic groundwater containing 135-350 mg NO3(-) L(-1) was treated in the IEMB system. A surface denitrification rate of 33 g NO3(-) per square meter of membrane per day was obtained at a nitrate loading rate of 360 g NO3(-) m(-3)d(-1), resulting in a nitrate removal efficiency of 85%.


Detecting polysaccharide antigen of Neisseria meningitidis group C in cerebrospinal fluid by dot-ELISA assay.
Cerebrospinal fluid (CSF) samples from 210 patients (200 with clinical evidence of bacterial meningitis, 10 with other clinical neurologic disease) were tested by a Dot-ELISA assay for detection of polysaccharide antigen of N. meningitidis group C. CSF samples were treated with EDTA 0.1 M, at pH 7.5 and heated to 90>C for 10 min. Polyclonal antiserum was purified by use of ethanol fractionation. The results were compared to those using bacterial culture (BC), latex agglutination (LA), counterimmunoelectrophoresis (CIE), and direct microscopy (DM) methods. Test results showed a correlation of 93.3%, 94.3%, 91.0% and 69.5% respectively, and sensitivity of 0.947 and specificity of 0.930. This study suggests that the dot-ELISA assay of CSF is a useful alternative technique for the diagnosis of group C meningitis.


Effect of raw soy flour, feeding regime, and azaserine on rat pancreas.
The combined effects of feeding rats increasing amounts of raw soy four, feeding regime (ad libitum vs one meal per day), and injection of azaserine on the incidence of pancreatic nodules were investigated over a period of 12 months. Food consumption and body weights of meal-fed rats were lower than those of their ad libitum counterparts. The difference in body weight between the ad libitum and meal-fed rats became greater as the level of raw soy flour in the diet increased. Azaserine injections did not affect food consumption or body weight. The weights of the pancreas (gm/100 gm BW) increased parallel to the level of raw soy flour in the diet. The survival rate of rats on diets containing 19% and 42% raw soy flour was greater on the meal-fed regime than in the ad libitum group, but the converse was true when the diet contained 80% raw soy flour. The number and severity of pancreatic nodules observed in azaserine-injected animals surviving at the end of 12 months increased in relation to the level of raw soy flour in the diet and was enhanced at each level by meal feeding.


Developing a tracking system for coagulation factor concentrates in southern Ontario.
In response to the transfusion- transmitted AIDS epidemic, Canadian authorities recommended the development of tracking systems and improved reporting of adverse events. This study describes the development of a verifiable and comprehensive regional tracking system for coagulation factor concentrates. The Hamilton- Niagara Regional Hemophilia Program received distribution and utilization data from Canadian Blood Services, 26 regional hospitals, and 70 individuals with bleeding disorders on home-based therapy. Purpose-specific software, the Canadian Hemophilia Assessment and Resource Management System (CHARMS), was used to store, monitor, analyze, and validate data. During a 1-year period (2001), all factor concentrates distributed in this region were accounted for. A higher proportion of FVIII and FIX concentrates (88 vs. 12%) was infused at home than in hospitals, and a higher proportion (63 vs. 28%) was used to prevent than to treat bleeds. During a period of shortage, a 5-percent reduction in utilization of both FVIII and FIX concentrates was documented. One recall was managed swiftly and efficiently. Two patients reported allergic skin reactions. A verifiable tracking system has been developed that can provide ongoing data for both clinical and administrative purposes. Data collection from patients needs to be made more efficient and real-time recording is an important future objective. Such a system can be instituted locally for less than 1.5 percent of the cost of the factor concentrate used.


Method To Detect Only Live Bacteria during PCR Amplification.
Ethidium monoazide (EMA) is a DNA cross-linking agent and eukaryotic topoisomerase II poison. We previously reported that the treatment of EMA with visible light irradiation (EMA + Light) directly cleaved chromosomal DNA of Escherichia coli (T. Soejima, K. Iida, T. Qin, H. Taniai, M. Seki, A. Takade, and S. Yoshida, Microbiol. Immunol. 51:763-775, 2007). Herein, we report that EMA + Light randomly cleaved chromosomal DNA of heat-treated, but not live, Listeria monocytogenes cells within 10 min of treatment. When PCR amplified DNA that was 894 bp in size, PCR final products from 10(8) heat-treated L. monocytogenes were completely suppressed by EMA + Light. When target DNA was short (113 bp), like the hly gene of L. monocytogenes, DNA amplification was not completely suppressed by EMA + Light only. Thus, we used DNA gyrase/topoisomerase IV and mammalian topoisomerase poisons (here abbreviated as T-poisons) together with EMA + Light. T-poisons could penetrate heat-treated, but not live, L. monocytogenes cells within 30 min to cleave chromosomal DNA by poisoning activity. The PCR product of the hly gene from 10(8) heat-treated L. monocytogenes cells was inhibited by a combination of EMA + Light and T-poisons (EMA + Light + T-poisons), but those from live bacteria were not suppressed. As a model for clinical application to bacteremia, we tried to discriminate live and antibiotic-treated L. monocytogenes cells present in human blood. EMA + Light + T-poisons completely suppressed the PCR product from 10(3) to 10(7) antibiotic-treated L. monocytogenes cells but could detect 10(2) live bacteria. Considering the prevention and control of food poisoning, this method was applied to discriminate live and heat-treated L. monocytogenes cells spiked into pasteurized milk. EMA + Light + T-poisons inhibited the PCR product from 10(3) to 10(7) heat-treated cells but could detect 10(1) live L. monocytogenes cells. Our method is useful in clinical as well as food hygiene tests.


An investigation of patterns of children's sedentary and vigorous physical activity throughout the week.
Participation in higher intensity activity (i.e. vigorous physical activity [VPA]) appears more consistently associated with lower adiposity, unfortunately little is known about the nature and patterns of VPA participation in children. To examine the volume and patterns of vigorous and sedentary activity during different segments of the week (weekend, school-based and out-of-school). We also investigated differences by sex, socioeconomic status (SES) and weight status. A cross-sectional study including 1568 UK children aged 9-10 years. Sedentary activity (mins), total activity (counts/min) and VPA (mins) were measured by accelerometry. Using a series of 2 level mixed effects linear regression models we tested differences across the segmented week (school time [0900-1500] vs. out-of-school time [0700-0900 & 1500-2100]; and weekday vs. weekend); all models were adjusted for sex, weight status (gender- and age-specific body mass index [BMI] cut points), SES, age and accelerometer registered wear time. Boys and girls accumulated higher VPA out-of-school compared to during school (boys mean ± SD 16.9 ± 9.6 vs 12.6 ± 5.8; girls, 13.1 ± 7.7 vs 8.2 ± 4.0, both p < 0.001); but there were no differences for weekday v weekend VPA (p > 0.05). Less time was spent sedentary on weekdays compared to weekends (p < 0.001). Although boys were more physically active and girls accumulated more sedentary time, the overall pattern in which their physical activity intensity varied across the various day segments was similar when stratified by weight status and SES; and large volumes of sedentary time were observed each hour across the day. The promotion of VPA during the weekend may hold the greatest promise for increasing VPA. Interventions aimed at increasing physical activity in 9-10 year old children should aim to target all children independent of sex, SES or weight status.


Barriers to and enablers of uptake of antiretroviral therapy in integrated HIV and tuberculosis treatment programmes in sub-Saharan Africa: a systematic review and meta-analysis.
Programmes that merge management of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) aim to improve HIV/TB co-infected patients' access to comprehensive treatment. However, several reports from sub-Saharan Africa (SSA) indicate suboptimal uptake of antiretroviral therapy (ART) even after integration of HIV and TB treatment. This study assessed ART uptake, its barriers and enablers in programmes integrating TB and HIV treatment in SSA. A systematic review was performed. Seven databases were searched for eligible quantitative, qualitative and mixed-methods studies published from March 2004 through July 2019. Random-effects meta-analysis was used to obtain pooled estimates of ART uptake. A thematic approach was used to analyse and synthesise data on barriers and enablers. Of 5139 references identified, 27 were included in the review: 23/27 estimated ART uptake and 10/27 assessed barriers to and/or enablers of ART uptake. The pooled ART uptake was 53% (95% CI: 42, 63%) and between-study heterogeneity was high (I2 = 99.71%, p < 0.001). WHO guideline on collaborative TB/HIV activities and sample size were associated with heterogeneity. There were statistically significant subgroup effects with high heterogeneity after subgroup analyses by region, guideline on collaborative TB/HIV activities, study design, and sample size. The most frequently described socioeconomic and individual level barriers to ART uptake were stigma, low income, and younger age group. The most frequently reported health system-related barriers were limited staff capacity, shortages in medical supplies, lack of infrastructure, and poor adherence to or lack of treatment guidelines. Clinical barriers included intolerance to anti-TB drugs, fear of drug toxicity, and contraindications to antiretrovirals. Health system enablers included good management of the procurement, supply, and dispensation chain; convenience and accessibility of treatment services; and strong staff capacity. Availability of psychosocial support was the most frequently reported enabler of uptake at the community level. In SSA, programmes integrating treatment of TB and HIV do not, in general, achieve high ART uptake but we observe a net improvement in uptake after WHO issued the 2012 guidelines on collaborative TB/HIV activities. The recurrence of specific modifiable system-level and patient-level factors in the literature reveals key intervention points to improve ART uptake in these programmes. Systematic review registration: CRD42019131933.


The neuropeptide F/nitric oxide pathway is essential for shaping locomotor plasticity underlying locust phase transition.
Behavioral plasticity is widespread in swarming animals, but little is known about its underlying neural and molecular mechanisms. Here, we report that a neuropeptide F (NPF)/nitric oxide (NO) pathway plays a critical role in the locomotor plasticity of swarming migratory locusts. The transcripts encoding two related neuropeptides, NPF1a and NPF2, show reduced levels during crowding, and the transcript levels of NPF1a and NPF2 receptors significantly increase during locust isolation. Both NPF1a and NPF2 have suppressive effects on phase-related locomotor activity. A key downstream mediator for both NPFs is nitric oxide synthase (NOS), which regulates phase-related locomotor activity by controlling NO synthesis in the locust brain. Mechanistically, NPF1a and NPF2 modify NOS activity by separately suppressing its phosphorylation and by lowering its transcript level, effects that are mediated by their respective receptors. Our results uncover a hierarchical neurochemical mechanism underlying behavioral plasticity in the swarming locust and provide insights into the NPF/NO axis.


Comparison of recovery patterns for patients undergoing coronary artery bypass grafting and minimally invasive direct coronary artery bypass in the early discharge period.
The purpose of this pilot study was to compare the postoperative problems, evaluation and response of symptoms, and functional status (physiologic and psychosocial functioning) during the early recovery period (2, 4, and 6 weeks after surgery) in 35 individuals who underwent coronary artery bypass grafting (n=24) or minimally invasive direct coronary artery bypass (n=11). The most frequent postoperative problem reported by the coronary artery bypass grafting group was an incisional infection (either sternal or leg); 26% reported infection at 2 and 4 weeks, and 21% at 6 weeks after surgery. Respiratory problems (pleural effusion, pneumonia) were the second most frequently reported problem, reported by 10% of the subjects at 2 and 4 weeks and by 16% at 6 weeks. Other, less frequent problems were severe nervousness, rhythm problems, and pericarditis. Minimally invasive direct coronary artery bypass patients reported fewer postoperative or cardiac-related problems, as only 5% indicated a problem with heart failure at both 2 and 4 weeks, and 36% reported being very nervous or having emotional problems at 4 weeks. Unlike postoperative problems, there were numerous similarities in postprocedural symptoms between these two groups. Fatigue, shortness of breath, and pain were the major symptoms reported postdischarge by both groups in this study. In addition, sleeping problems were also fairly prevalent in the coronary artery bypass grafting group, which is understandable, considering the fatigue ratings. Physiologic and psychosocial functioning varied minimally between the two procedures. While there were many similarities in the recovery patterns of both groups, the occurrence of postprocedural problems and symptoms of these two patient groups should be considered by clinicians to further tailor patient education.


Local and systemic regulation of sulfur homeostasis in roots of Arabidopsis thaliana.
Nutrients are limiting for plant growth and vigour. Hence, nutrient uptake and homeostasis must be adjusted to the needs of the plant according to developmental stages and environmental conditions. A split-root system was applied to analyse the systemic and local response of Arabidopsis thaliana to sulfur starvation. Arabidopsis thaliana plants in which only one root half was starved while the other root half was supplied with sulfate were analysed at the metabolic and transcriptional level. No systemic induction of sulfate uptake or expression of sulfate starvation marker genes was observed in split-roots sufficiently supplied with sulfate. Our data suggest that no activation of sulfur uptake takes part in sulfur-supplied root patches when the general sulfur status declines. When comparing roots of fully sulfate-starved plants with sulfate-starved split-root roots, expression of several potentially OAS responsive genes was attenuated in split-roots depending on the shoot sulfate status and the local root O-acetylserine concentration. In contrast, high-affinity sulfate transporters displayed similar expression in sulphate-starved split-roots and the corresponding controls. Feeding of (35) SO(4) (2-) to the shoot or to either part of a split-root system revealed that sulfate is the most prominent mobile sulfur-containing compound within the plant. Hence, we postulate a model whereby the soil sulfate availability regulates the sulfate uptake system of roots while the shoot sulfur status modulates the local O-acetylserine response in the root by passive 'plant sulfur status-dependent' transport of sulfate.


Sodium salicylate induces apoptosis in HCT116 colorectal cancer cells through activation of p38MAPK.
Sodium salicylate is known to induce apoptosis in a variety of cancer cells. However, the molecular mechanism for salicylate-induced apoptosis is yet unclear. Here we show that in HCT116 colon carcinoma cells, 10 mM sodium salicylate induces caspase-3 activation and degradation of its substrates, poly(ADP-ribose) polymerase (PARP), beta-catenin, and retinoblastoma (Rb). In contrast, sodium salicylate did not exert any significant effects on the expression of Fas L that is implicated in extrinsic apoptotic pathway and the levels of Bcl-2 family proteins, Bcl-2, Bcl-xsl, and Bad, which are involved in intrinsic apoptotic pathway, and anti-apoptotic molecules, c-IAP1 and HSP73. In addition, 10 mM salicylate induced p53 tumor suppressor protein that plays an important role in cell cycle arrest or apoptosis and the induction seemed to be linked to its phosphorylation at Set 15. To investigate the signal pathways for salicylate-induced apoptosis, we examined the effects of sodium salicylate on protein kinase activities. Sodium salicylate activated p38MAPK through phosphorylation at Thr 180/Tyr 182 and Akt/PKB at Ser 473, whereas it partially activated ERK1/2 through its phosphorylation at Thr 202/Tyr 204. We also show that SB203580 (a specific p38MAPK inhibitor), but not other protein kinase inhibitors (PD98059, LY294002, and wortmannin), significantly prevented salicylate-induced apoptosis. These results suggest that sodium salicylate-induced apoptosis in HCT116 colorectal cancer cells is mediated by p38MAPK.


Misfit of implant prostheses and its impact on clinical outcomes. Definition, assessment and a systematic review of the literature.
Compromised fit between the contact surfaces of screw-retained implant-supported fixed dentures (IFDs) is thought to create uncontrolled strains in the prosthetic components and peri-implant tissues, thus evoking biological and technical complications such as bone loss, screw loosening, component fractures and, at worst, loss of implants or prostheses. The aim of this systematic review was to evaluate the impact of marginal misfit on the clinical outcomes of IFDs, and to elucidate definition and assessment methods for passive fit. A systematic review of the literature was conducted with a PICO question: "For partially or complete edentulous subjects with screw-retained IFDs, does the marginal misfit at the implant-prosthesis interfaces have an impact on the clinical outcomes?". A literature search was performed electronically in PubMed (MEDLINE) with the help of Boolean operators to combine key words, and by hand search in relevant journals. English written in vivo studies published before August 31, 2016 that reported on both clinical outcome and related implant prosthesis misfit (gap, strains, torque) were selected using predetermined inclusion criteria. The initial search yielded 2626 records. After screening and a subsequent filtering process, five human and five animal studies were included in the descriptive analysis. The selected studies used different methods to assess misfit (linear distortion, vertical gap, strains, screw torque). While two human studies evaluated the biological response and technical complications prospectively over 6 and 12 months, the animal studies had an observation period < 12 weeks. Four human studies analysed retrospectively the 3 to 32 years' outcomes. Screw-related complications were observed, but biological sequelae could not be confirmed. Although the animal studies had different designs, bone adaptation and implant displacement was found in histological analyses. Due to the small number of studies and the heterogenic designs and misfit assessment methods, no meta-analysis of the data could be performed. The current literature provides insufficient evidence as to the effect of misfit at the prosthesis-implant interface on clinical outcomes of screw-retained implant-supported fixed dentures. Marginal gaps and static strains due to screw tightening were not found to have negative effects on initial osseointegration or peri-implant bone stability over time. Based on two clinical studies, the risk for technical screw-related complications was slightly higher. While the degree of tolerable misfit remains a matter of debate, the present data do not imply that clinicians neglect good fit, but aim to achieve the least misfit possible. Conflict of interest statement: The authors declare no conflict of interest. The review was conducted as part of the 2016 Foundation of Oral Rehabilitation Consensus Conference on "Prosthetic Protocols in Implant-based Oral Rehabilitation".


Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis.
Interleukin-6 (IL-6) is a key player in systemic arthritis, involved in inflammation and joint destruction. IL-6 signalling has also been revealed in nerve cells. Recently, IL-6 and in particular IL-6 together with its soluble IL-6 receptor (sIL-6R) were shown to induce a long-lasting robust sensitization of joint nociceptors for mechanical stimuli which was difficult to reverse, suggesting that IL-6 signalling plays a significant role in the generation and maintenance of arthritic pain. Here we tested in a preclinical model of arthritis, antigen-induced arthritis (AIA) in the rat, whether systemic or local neutralization of IL-6/sIL-6R complexes with soluble glycoprotein 130 (sgp130) alters arthritic pain and how sgp130 influences the inflammatory process in AIA. Rats with AIA were either treated with sgp130 or saline intra-peritoneally or intra-articularly (each group n = 9). Then, pain-related and locomotor behaviour, as well as joint swelling, were measured during an observation period of 21 days, followed by histopathological end-point analysis for inflammatory and destructive changes. A single intra-articular application of sgp130 at the time of AIA induction barely reduced the development of AIA, but significantly attenuated pain-related behaviour, that is, primary mechanical hyperalgesia in the acute phase of AIA. By contrast, repeated systemic application of sgp130 after onset of AIA only slightly attenuated pain at a late stage of AIA. None of the treatments reduced secondary hyperalgesia. Furthermore, in the present study joint destruction at 21 days was significantly attenuated after intra-articular sgp130 treatment, but not after systemic sgp130. In addition to its role in chronic inflammation, IL-6 in the joint plays a significant role in the generation and maintenance of arthritic joint pain at acute and chronic stages of AIA. The particular effectiveness of intra-articular injection of sgp130 indicates, first, that IL-6/sIL-6R in the inflamed joint, rather than circulating IL-6/sIL-6R, is responsible for the generation of hyperalgesia, and, second, that early neutralization of IL-6/sIL-6R is particularly successful in producing antinociception. Furthermore, neutralization of IL-6/sIL-6R (and possibly other cytokines which use the transmembrane signal-transducing subunit gp130) directly at the site of joint inflammation seems to be effective in the prevention of joint destruction.


Of two minds: Sceptic-proponent collaboration within parapsychology.
The first author, a proponent of evidence for psychic ability, and the second, a sceptic, have been conducting a systematic programme of collaborative sceptic-proponent research in parapsychology. This has involved carrying out joint experiments in which each investigator individually attempted to mentally influence the electrodermal activity of participants at a distant location. The first two collaborations obtained evidence of 'experimenter effects', that is, experiments conducted by the proponent obtained significant results but those conducted by the sceptic did not. This paper describes a new collaborative study that attempted to replicate our previous findings and explore potential explanations for past results. The new study failed to replicate our previous findings. The paper investigates whether the results obtained in our initial studies may have been caused by a genuine psychic effect, and this third experiment failed to replicate this finding because some aspect of the study disrupted the production of that effect, or whether the results from our first two studies represented chance findings or undetected subtle artifacts, and the results obtained in the present study accurately reflect the absence of a remote detection of staring effect. The implications of this work are discussed, along with the benefits of conducting collaborative work for resolving disagreements in other controversial areas of psychology.


Muscle recession with a suture loop in rabbits.
We recessed extraocular muscles in rabbits using loops of silk sutures. The effectiveness of the pseudotendons produced depended on their relation to the functional equator of the eye and on the length adherent to the sclera. Loops about 5 mm long inserted at or near the functional equator produced effective pseudotendons. If the loops were inserted in front of the functional equator they adhered to the sclera and the advantage of using them was negated.


Determination of indeloxazine in plasma by liquid chromatography and gas chromatography-mass spectrometry.
Two methods have been developed for the quantitative determination of indeloxazine, a cerebral activator, in plasma by HPLC or GC-MS. After addition of viloxazine as the internal standard, indeloxazine was extracted from alkalinized plasma. In the HPLC method, the plasma extract was treated with 5-dimethylamino-1-naphthalenesulfonyl chloride and analyzed by HPLC with fluorescence detection. In the GC-MS method, the two plasma compounds were converted to their pentafluoropropionyl derivatives for selected-ion monitoring. The limits of detection were 5 and 2 ng/mL for the HPLC and GC-MS methods, respectively. When plasma samples obtained by giving indeloxazine hydrochloride to volunteers were analyzed by the two methods, good correlation between the data was obtained (r = 0.9901).


Quantitative Trait Loci (QTL) Mapping for Glycinin and β-Conglycinin Contents in Soybean (Glycine max L. Merr.).
Compared to β-conglycinin, glycinin contains 3-4 times the methionine and cysteine (sulfur-containing amino acids), accounting for approximately 40 and 30%, respectively, of the total storage protein in soybean. Increasing the soybean storage protein content while improving the ratio of glycinin to β-conglycinin is of great significance for soybean breeding and soy food products. The objective of this study is to analyze the genetic mechanism regulating the glycinin and β-conglycinin contents of soybean by using a recombinant inbred line (RIL) population derived from a cross between Kefeng No. 1 and Nannong 1138-2. Two hundred and twenty-one markers were used to map quantitative trait loci (QTLs) for glycinin (11S) and β-conglycinin (7S) contents, the ratio of glycinin to β-conglycinin (RGC), and the sum of glycinin and β-conglycinin (SGC). A total of 35 QTLs, 3 pairs of epistatic QTLs, and 5 major regions encompassing multiple QTLs were detected. Genes encoding the subunits of β-conglycinin were localized to marker intervals sat_418-satt650 and sat_196-sat_303, which are linked to RGC and SGC; marker sat_318, associated with 11S, 7S, and SGC, was located near Glyma10g04280 (Gy4), which encodes a subunit of glycinin. These results, which take epistatic interactions into account, will improve our understanding of the genetic basis of 11S and 7S contents and will lay a foundation for marker-assisted selection (MAS) breeding of soybean and improving the quality of soybean products.


Induced Pluripotent Stem Cell Technology: A Paradigm Shift in Medical Science for Drug Screening and Disease Modeling.
Induced Pluripotent Stem Cell (IPSC) Technology is the most advanced research as it offers an attractive alternative for establishing patient-specific IPSCs to recapitulate phenotypes of not only monogenic diseases (viz. Thalassaemia, Sickle cell anemia, Haemophilia, Tay-Sachs disease), but also late-onset polygenic diseases (viz. Parkinson's disease, Alzheimer's disease, schizophrenia). Over the hindsight, numerous studies of the past and current scientists have led to the production, maturation and understanding of induced pluripotent stem cell technology and its use in basic and clinical research. A systematic search of peer-reviewed scientific literature and clinical trials in public databases were carried out to summarize the evidence on the use of IPSC. Current review sheds light upon the use of patient-derived iPSC models in drug toxicity, screening and discovery which have been derived after referring to more than 200 articles in literature. Furthermore, their use as disease models was also studied signifying the versatility of iPSC lines. Through this review, we describe the advent of iPSC technology, where we comprehensively cover the generation of iPSCs and their characterization along with their prospective applications using IPSC banks in disease modeling and drug screening.


Patient-Generated Health Data in Pediatric Asthma: Exploratory Study of Providers' Information Needs.
Adolescents are using mobile health apps as a form of self-management to collect data on symptoms, medication adherence, and activity. Adding functionality to an electronic health record (EHR) to accommodate disease-specific patient-generated health data (PGHD) may support clinical care. However, little is known on how to incorporate PGHD in a way that informs care for patients. Pediatric asthma, a prevalent health issue in the United States with 6 million children diagnosed, serves as an exemplar condition to examine information needs related to PGHD. In this study we aimed to identify and prioritize asthma care tasks and decisions based on pediatric asthma guidelines and identify types of PGHD that might support the activities associated with the decisions. The purpose of this work is to provide guidance to mobile health app developers and EHR integration. We searched the literature for exemplar asthma mobile apps and examined the types of PGHD collected. We identified the information needs associated with each decision in accordance with consensus-based guidelines, assessed the suitability of PGHD to meet those needs, and validated our findings with expert asthma providers. We mapped guideline-derived information needs to potential PGHD types and found PGHD that may be useful in meeting information needs. Information needs included types of symptoms, symptom triggers, medication adherence, and inhaler technique. Examples of suitable types of PGHD were Asthma Control Test calculations, exposures, and inhaler use. Providers suggested uncontrolled asthma as a place to focus PGHD efforts, indicating that they preferred to review PGHD at the time of the visit. We identified a manageable list of information requirements derived from clinical guidelines that can be used to guide the design and integration of PGHD into EHRs to support pediatric asthma management and advance mobile health app development. Mobile health app developers should examine PGHD information needs to inform EHR integration efforts.


Enrichment and nonhuman primates: "first, do no harm".
Since the 1998 publication of The Psychological Well-Being of Nonhuman Primates by the National Research Council, and the 1991 implementation of the 1985 Animal Welfare Act Amendment, many formal and informal nonhuman primate enrichment programs have been put into practice. Reports of their successes and failures, however, are few. All programs have at least two things in common: (1) They are best when designed and maintained by teams of individuals with species-specific expertise; (2) the members of those teams, the stakeholders, usually include principal investigators, animal care and use committee members, veterinarians, and animal care staff. Discussions in this article address general principles about enrichment, goals of such programs from the perspective of each of the major stakeholders, and recently published sources of related information. These discussions follow the central premise that enrichment should benefit all involved and "First, do no harm."


Urokinase-type plasminogen activator mediates basic fibroblast growth factor-induced bovine endothelial cell migration independent of its proteolytic activity.
The dependence of urokinase-type plasminogen activator (uPA) induction on endogenous basic fibroblast growth factor (bFGF) activity during endothelial cell migration was investigated utilizing a combination of wounded endothelial cell monolayers and substrate overlay techniques. Purified polyclonal rabbit immunoglobulin G (IgG) against bFGF blocked the appearance of uPA-dependent lytic activity normally observed at the edge of a wounded bovine aortic endothelial (BAE) cell monolayer. Additionally, the migration of cells into the denuded area was inhibited 30-50% by antibodies either to bFGF or to bovine uPA. Incubation of wounded monolayers with either purified bovine uPA or agents able to induce PA activity, such as phorbol myristate acetate (PMA), vanadate, or bFGF, resulted in enhanced migration of cells (28-50%). Anti-bovine uPA IgG blocked a significant fraction (25%) of BAE cell migration induced by exposure to exogenous bFGF. The role of uPA in migration of wounded BAE cells was not dependent on plasmin generation. Furthermore, the amino terminal fragment (ATF) of human recombinant (hr) uPA, which is enzymatically inactive, stimulated endothelial cell movement in the presence of anti-bFGF IgG. These results suggest that BAE cell migration from the edge of a wounded monolayer is dependent upon local increases of uPA mediated by endogenous bFGF. Moreover, the data support the conclusion that migration is stimulated via a signalling mechanism dependent upon occupancy of the uPA receptor but independent of uPA-mediated proteolysis.


Activation of transient receptor potential ankyrin 1 evokes nociception through substance P release from primary sensory neurons.
To examine mechanisms underlying substance P (SP) release from primary sensory neurons in response to activation of the non-selective cation channel transient receptor potential ankyrin 1 (TRPA1), SP release from cultured rat dorsal root ganglion neurons was measured, using radioimmunoassay, by stimulating TRPA1 with allyl isothiocyanate (AITC), a TRPA1 agonist. AITC-evoked SP release occurred in a concentration- and time-dependent manner. Interestingly, p38 mitogen-activated protein kinase (p38) inhibitor SB203580 significantly attenuated AITC-evoked SP release. The in vivo effect of AITC-evoked SP release from primary sensory neurons in mice was evaluated. Hind paw intraplantar injection of AITC induced nociceptive behaviors and inflammation (edema, thermal hyperalgesia). AITC-induced thermal hyperalgesia and edema were inhibited by intraplantar pre-treatment with either SB203580 or neurokinin-1 receptor antagonist CP96345. Moreover, intrathecal pre-treatment with either CP96345 or SB203580 inhibited AITC-induced nociceptive behaviors and thermal hyperalgesia. Immunohistochemical studies demonstrated that intraplantar AITC injection induced the phosphorylation of p38 in mouse dorsal root ganglion neurons containing SP. These findings suggest that activation of TRPA1 evokes SP release from the primary sensory neurons through phosphorylation of p38, subsequent nociceptive behaviors and inflammatory responses. Furthermore, the data also indicate that blocking the effects of TRPA1 activation at the periphery leads to significant antinociception.


Magnetic resonance imaging compared with biopsy in the diagnosis of brainstem diseases of childhood: a multicenter review.
Data analysis was performed in a multicenter study to evaluate magnetic resonance (MR) imaging for classification of brain tumors, prognosis, and prediction of tumor histological diagnosis. The clinical, MR imaging, and histological findings obtained in 142 pediatric cases of brainstem disease were assessed in a multicenter study performed as a blinded review. Clinical data were available in 142 cases, histopathological findings in 126, and MR images in 131. The subgroup of cases involving brainstem gliomas (78 cases) was analyzed separately. Images that met criteria for evaluation were reviewed in random order by three experienced observers who were initially blinded to clinical data as well as histopathological diagnoses. Subsequently, the images were randomized again and provided to the observers for review together with the clinical symptoms of the specific patients. The three observers were able to correctly identify lesions as tumors or nontumorous disease on MR images in 99, 96, and 95% of cases, resulting in an overall sensitivity of 0.94, a specificity of 0.43, a positive predictive value of 0.96, and a negative predictive value of 0.45. Awareness of clinical symptoms did not change the results. Based on 14 imaging criteria together with the patient's clinical history and symptoms, laboratory data (results of cerebrospinal fluid analysis as well as infectious and immunological parameters), and imaging follow up, a diagnosis of brainstem tumor, as opposed to demyelination, encephalitis, or granuloma, could generally be made. Given these findings, there is only rarely a need for biopsy, and in those patients in whom it is considered, the potential costs and benefits must be carefully assessed on a case-by-case basis.


Monte Carlo and analytical calculation of proton pencil beams for computerized treatment plan optimization.
Proton pencil beams in water, in a format suitable for treatment planning algorithms and covering the radiotherapy energy range (50-250 MeV), have been calculated using a modified version of the Monte Carlo code PTRAN. A simple analytical model has also been developed for calculating proton broad-beam dose distributions which is in excellent agreement with the Monte Carlo calculations. Radial dose distributions are also calculated analytically and narrow proton pencil-beam dose distributions derived. The physical approximations in the Monte Carlo code and in the analytical model together with their limitations are discussed. Examples showing the use of the calculated set of proton pencil beams as input to an existing photon treatment planning algorithm based on biological optimization are given for fully 3D scanned proton pencil beams; these include intensity modulated beams with range shift and scanning in the transversal plane.


Zingiber officinale-Derived Extracellular Vesicles Attenuate Bleomycin-Induced Pulmonary Fibrosis Trough Antioxidant, Anti-Inflammatory and Protease Activity in a Mouse Model.
Idiopathic pulmonary fibrosis (IPF) is the most frequent and severe idiopathic interstitial pneumonia. It is a chronic and progressive disease with a poor prognosis and is a major cause of morbidity and mortality. This disease has no cure; therefore, there is a clinical need to search for alternative treatments with greater efficacy. In this study, we aimed to evaluate the effect of extracellular vesicles (EVs) from Zingiber officinale (EVZO) in a murine model of bleomycin (BLM)-induced IPF administered through an osmotic minipump. EVZO had an average size of 373 nm and a spherical morphology, as identified by scanning electron microscopy. Label-free proteomic analysis of EVZOs was performed by liquid chromatography coupled to mass spectrometry, and 20 proteins were identified. In addition, we demonstrated the protease activity of EVZO by gelatin-degrading zymography assay and the superoxide dismutase (SOD) activity of EVZO by an enzymatic assay. In the BLM-induced IPF mouse model, nasal administration of 50 μg of EVZO induced recovery of alveolar space size and decreased cellular infiltrate, collagen deposition, and expression of α-SMA-positive cells. Additionally, EVZO inhibited inflammatory markers such as iNOS and COX-2, lipid peroxidation, and apoptotic cells. These results show that EVZO may represent a novel natural delivery mechanism to treat IPF.


Investigation of fatty acid elongation and desaturation steps in Fusarium lateritium by quantitative two-dimensional deuterium NMR spectroscopy in chiral oriented media.
The origin of hydrogen atoms during fatty acid biosynthesis in Fusarium lateritium has been quantified by isotope tracking close to natural abundance. Methyl linoleate was isolated from F. lateritium grown in natural abundance medium or in medium slightly enriched with labeled water, glucose, or acetate, and the (2)H incorporation was determined by quantitative (2)H-{(1)H} NMR in isotropic and chiral oriented solvents. Thus, the individual ((2)H/(1)H)(i) ratio at each pro-R and pro-S hydrogen position of the CH(2) groups along the chain can be analyzed. These values allow the isotope redistribution coefficients (a(ij)) that characterize the specific source of each hydrogen atom to be related to the nonexchangeable hydrogen atoms in glucose and to the medium water. In turn, these can be related to the stereoselectivity that operates during the introduction or removal of hydrogens along the fatty acid chain. First, at even CH(2) the pro-S hydrogen comes only from water by protonation, whereas the pro-R hydrogen is introduced partly via acetate but principally from water. Second, the nonexchangeable hydrogens of glucose (positions H-6,6 and H-1) are shown to be introduced to the odd CH(2) via the NAD(P)H pool used by both reductases involved in the elongation steps of the fatty acid chain. Third, it is proved that hydrogens removed at sites 9,10 and 12,13 during desaturation by Delta(9)- and Delta(12)-desaturases are pro-R, and that during these desaturation steps alpha-secondary kinetic isotope effects occur at the 9 and 12 positions and not at the 10 and 13 positions.


Gait Training With Visual Feedback and Proprioceptive Input to Reduce Gait Asymmetry in Adults With Cerebral Palsy: A Case Series.
The purpose of this case series was to investigate the feasibility of using visual feedback on gait asymmetry during gait retraining and whether this leads to reduced asymmetry, improvement in gait speed, cost of walking, and dynamic balance in ambulant adults with cerebral palsy (CP). Five adults with CP, who were ambulatory and had step length or stance time asymmetry, trained for 18 sessions on a split-belt treadmill with concurrent visual feedback from a virtual environment. Training also included overground gait training to encourage transfer of learning. All participants reduced gait asymmetry and improved on outcomes at posttest and follow-up. Outcome measures and training protocols were feasible in this sample of convenience of adults with CP who were ambulatory and who did not have visual impairment. The adults with CP in this study demonstrated individual improvements in gait and balance following training.


Transcriptome analysis of the phytobacterium Xylella fastidiosa growing under xylem-based chemical conditions.
Xylella fastidiosa is a xylem-limited bacterium responsible for important plant diseases, like citrus-variegated chlorosis (CVC) and grapevine Pierce's disease (PD). Interestingly, in vitro growth of X. fastidiosa in chemically defined media that resemble xylem fluid has been achieved, allowing studies of metabolic processes used by xylem-dwelling bacteria to thrive in such nutrient-poor conditions. Thus, we performed microarray hybridizations to compare transcriptomes of X. fastidiosa cells grown in 3G10-R, a medium that resembles grape sap, and in Periwinkle Wilt (PW), the complex medium traditionally used to cultivate X. fastidiosa. We identified 299 transcripts modulated in response to growth in these media. Some 3G10R-overexpressed genes have been shown to be upregulated in cells directly isolated from infected plants and may be involved in plant colonization, virulence and environmental competition. In contrast, cells cultivated in PW show a metabolic switch associated with increased aerobic respiration and enhanced bacterial growth rates.


Anti-CCP antibody levels are not associated with MS: results from a case-control study.
Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS). Anticyclic citrullinated peptide (anti-CCP) antibody is used in the early diagnosis of rheumatoid arthritis (RA). The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years), 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years), and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years) were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA). The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls (P < 0.001). Moreover, anti-CCP antibody was positive in 43 (83%) patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores (r = -0.250). In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.


Manual annotation of Drosophila genes: a Genomics Education Partnership protocol.
Annotating the genomes of multiple species allows us to analyze the evolution of their genes. While many eukaryotic genome assemblies already include computational gene predictions, these predictions can benefit from review and refinement through manual gene annotation. The Genomics Education Partnership (GEP; https://thegep.org/) developed a structural annotation protocol for protein-coding genes that enables undergraduate student and faculty researchers to create high-quality gene annotations that can be utilized in subsequent scientific investigations. For example, this protocol has been utilized by the GEP faculty to engage undergraduate students in the comparative annotation of genes involved in the insulin signaling pathway in 27 Drosophila species, using D. melanogaster as the reference genome. Students construct gene models using multiple lines of computational and empirical evidence including expression data (e.g., RNA-Seq), sequence similarity (e.g., BLAST and multiple sequence alignment), and computational gene predictions. Quality control measures require each gene be annotated by at least two students working independently, followed by reconciliation of the submitted gene models by a more experienced student. This article provides an overview of the annotation protocol and describes how discrepancies in student submitted gene models are resolved to produce a final, high-quality gene set suitable for subsequent analyses. The protocol can be adapted to other scientific questions (e.g., expansion of the Drosophila Muller F element) and species (e.g., parasitoid wasps) to provide additional opportunities for undergraduate students to participate in genomics research. These student annotation efforts can substantially improve the quality of gene annotations in publicly available genomic databases.


UBC-Nepal expedition: peripheral fatigue recovers faster in Sherpa than lowlanders at high altitude.
The reduced oxygen tension of high altitude compromises performance in lowlanders. In this environment, Sherpa display superior performance, but little is known on this issue. Sherpa present unique genotypic and phenotypic characteristics at the muscular level, which may enhance resistance to peripheral fatigue at high altitude compared to lowlanders. We studied the impact of gradual ascent and exposure to high altitude (5050 m) on peripheral fatigue in age-matched lowlanders and Sherpa, using intermittent electrically-evoked contractions of the knee extensors. Peripheral fatigue (force loss) was lower in Sherpa during the first part of the protocol. Post-protocol, the rate of force development and contractile impulse recovered faster in Sherpa than in lowlanders. At any time, indices of muscle oxygenation were not different between groups. Muscle contractile properties in Sherpa, independent of muscle oxygenation, were less perturbed by non-volitional fatigue. Hence, elements within the contractile machinery contribute to the superior physical performance of Sherpa at high altitude. Altitude-related acclimatisation is characterised by marked muscular adaptations. Lowlanders and Sherpa differ in their muscular genotypic and phenotypic characteristics, which may influence peripheral fatigability at altitude. After gradual ascent to 5050 m, 12 lowlanders and 10 age-matched Sherpa (32 ± 10 vs. 31 ± 11 years, respectively) underwent three bouts (separated by 15 s rest) of 75 intermittent electrically-evoked contractions (12 pulses at 15 Hz, 1.6 s between train onsets) of the dominant leg quadriceps, at the intensity which initially evoked 30% of maximal voluntary force. Trains were also delivered at minutes 1, 2 and 3 after the protocol to measure recovery. Tissue oxygenation index (TOI) and total haemoglobin (tHb) were quantified by a near-infrared spectroscopy probe secured over rectus femoris. Superficial femoral artery blood flow was recorded using ultrasonography, and delivery of oxygen was estimated (eDO2 ). At the end of bout 1, peak force was greater in Sherpa than in lowlanders (91.5% vs. 84.5% baseline, respectively; P < 0.05). Peak rate of force development (pRFD), the first 200 ms of the contractile impulse (CI200 ), and half-relaxation time (HRT) recovered faster in Sherpa than in lowlanders (percentage of baseline at 1 min: pRFD: 89% vs. 74%; CI200 : 91% vs. 80%; HRT: 113% vs. 123%, respectively; P < 0.05). Vascular measures were pooled for lowlanders and Sherpa as they did not differ during fatigue or recovery (P < 0.05). Mid bout 3, TOI was decreased (90% baseline) whereas tHb was increased (109% baseline). After bout 3, eDO2 was markedly increased (1266% baseline). The skeletal muscle of Sherpa seemingly favours repeated force production at altitude for similar oxygen delivery compared to lowlanders.


Extending pressure-matching to inhomogeneous systems via local-density potentials.
Bottom-up coarse-grained models describe the intermolecular structure of all-atom (AA) models with desirable accuracy and efficiency. Unfortunately, structure-based models for liquids tend to dramatically overestimate the thermodynamic pressure and, consequently, tend to vaporize under ambient conditions. By employing a volume potential to introduce additional cohesion, self-consistent pressure-matching provides a simple and robust method for accurately reproducing the pressure equation of state (EoS) for homogeneous fluids, while still preserving an accurate description of intermolecular structure. Because they depend upon the global density, though, volume potentials cannot be directly employed for inhomogeneous systems, such as liquid-vapor interfaces. In the present work, we demonstrate that volume potentials can be readily adapted as potentials of the local density. The resulting local-density potentials provide an accurate description of the structure, pressure EoS, and local density fluctuations of an AA model for liquid methanol. Moreover, we demonstrate that very slight modifications to these local-density potentials allow for a quantitative description of either local or global density fluctuations. Most importantly, we demonstrate that the resulting potentials, which were parameterized to describe a homogeneous liquid, also generate stable liquid-vapor coexistence. However, further work is necessary to more accurately reproduce the interfacial density profile.


Geometrical models of left ventricular contraction from MRI of the normal and spontaneously hypertensive rat heart.
This study develops a quantitative analysis and model for the differences in left ventricular dynamics in normal and spontaneously hypertensive rats, as determined using non-invasive magnetic resonance imaging (MRI). We emerge with a characterization of the geometrical changes in the left ventricle resulting from hypertension. In addition, the techniques we have adopted are potentially applicable to the study of other disease models for important human cardiac pathologies. A gradient-echo multislice imaging sequence (echo time 4.3 ms) achieved complete image coverage of the heart at high time resolution (13 ms) through the cardiac cycle. Cardiac anatomy in two age-matched groups of young adult (8 and 12 weeks old) normal Wistar-Kyoto (WKY, n = 8) and spontaneously hypertensive rats (SHR, n = 8) was imaged in synchrony with the electrocardiographic R wave in defined planes both parallel and perpendicular to the principal cardiac axis. The transverse left ventricular image sections were circularly symmetrical; this permitted application of different analytical models for the three-dimensional geometry of the epi- and endocardial borders. An ellipsoidal figure of revolution offered an effective description of the three-dimensional left ventricular geometry throughout the cardiac cycle in both normal WKY and SHR animals. The model successfully characterized both the dynamic changes in the shape of the left ventricle through the cardiac cycle and the pathological alterations resulting from spontaneous hypertension. The elliptical model also formed the basis of a simple stress distribution analysis. Such parametric descriptions thus provided a useful alternative to more complex finite element analyses of cardiac function. The eccentricity of the ventricle was characterized by an ellipticity factor a, where a = 1 for a sphere and a < 1 for a prolate ellipsoid. At end systole, the endocardial surface of the left ventricle gave a = 0.43+/-0.02 and 0.49+/-0.02 for the WKY and SHR animals respectively (probability, P < 0.05). At end diastole, the endocardial surface of the left ventricle gave a = 0.58+/-0.02 and 0.63+/-0.02 for the WKY and SHR animals respectively (P < 0.05). Such a difference in ventricular shape was a potential adaptation to increased blood pressure. Hypertension thus altered the left ventricular ellipticity to give a more spherical geometry compared with the normal rats.


Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae.
The use of fentanyl during pregnancy, whether by prescription or illicit use, may result in high blood levels that pose an early risk to fetal development. However, little is known regarding the neurotoxicity that might arise from excessive fentanyl exposure in growing organisms, particularly drug-related withdrawal symptoms. In this study, zebrafish embryos were exposed to fentanyl solutions (0.1, 1, and 5 mg/L) for 5 days post fertilization (dpf), followed by a 5-day recovery period, and then the larvae were evaluated for photomotor response, anxiety behavior, shoaling behavior, aggression, social preference, and sensitization behavior. Fentanyl solutions at 1 and 5 mg/L induced elevated anxiety, decreased social preference and aggressiveness, and behavioral sensitization in zebrafish larvae. The expression of genes revealed that embryonic exposure to fentanyl caused substantial alterations in neural activity (bdnf, c-fos) and neuronal development and plasticity (npas4a, egr1, btg2, ier2a, vgf). These results suggest that fentanyl exposure during embryonic development is neurotoxic, highlighting the importance of zebrafish as an aquatic species in research on the neurobehavioral effects of opioids in vertebrates.


Food Administration and Not Genetic Variants Causes Pharmacokinetic Variability of Tadalafil and Finasteride.
Tadalafil and finasteride are used in combination for the management of benign prostatic hyperplasia (BPH). Genetic variations in genes involved in the metabolism and transport of tadalafil or finasteride (i.e., pharmacogenes) could affect their pharmacokinetic processes altering their drug exposure, efficacy, and toxicity. The main objective of this study was to investigate the effects of variants in pharmacogenes on the pharmacokinetics of tadalafil and finasteride. An exploratory candidate gene study involving 120 variants in 33 genes was performed with 66 male healthy volunteers from two bioequivalence clinical trials after administration of tadalafil/finasteride 5 mg/5 mg under fed or fasting conditions. Afterwards, a confirmatory study was conducted with 189 male and female volunteers receiving tadalafil 20 mg formulations in seven additional bioequivalence clinical trials. Regarding tadalafil, fed volunteers showed higher area in the time-concentration curve (AUC∞), maximum plasma concentration (Cmax), and time to reach Cmax (tmax) compared to fasting volunteers; male volunteers also showed higher AUC∞ and Cmax compared to female volunteers. Furthermore, fed volunteers presented higher finasteride AUC∞, Cmax and tmax compared to fasting individuals. Variants in ABCC3, CYP1A2, CES1, NUDT15, SLC22A1/A2 and UGT2B10 were nominally associated with pharmacokinetic variation in tadalafil and/or finasteride but did not remain significant after correction for multiple comparisons. Genetic variation did not demonstrate to clinically impact on the pharmacokinetics of finasteride and tadalafil; however, additional studies with larger sample sizes are needed to assess the effect of rare variants, such as CYP3A4*20 or *22, on tadalafil and finasteride pharmacokinetics.


A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS.
To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse. Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration. The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a "non-inferiority effect" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms. Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%).


Characterizing Highly Cited Papers in Mass Cytometry through H-Classics.
Mass cytometry (CyTOF) is a relatively novel technique for the multiparametric analysis of single-cell features with an increasing central role in cell biology, immunology, pharmacology, and biomedicine. This technique mixes the fundamentals of flow cytometry with mass spectrometry and is mainly used for in-depth studies of the immune system and diseases with a significant immune load, such as cancer, autoimmune diseases, and viral diseases like HIV or the recently emerged COVID-19, produced by the SARS-CoV-2 coronavirus. The objective of this study was to provide a useful insight into the evolution of the mass cytometry research field, revealing the knowledge structure (conceptual and social) and authors, countries, sources, documents, and organizations that have made the most significant contribution to its development. We retrieved 937 articles from the Web of Science (2010-2019), analysed 71 Highly Cited Papers (HCP) through the H-Classics methodology and computed the data by using Bibliometrix R package. HCP sources corresponded to high-impact journals, such as Nature Biotechnology and Cell, and its production was concentrated in the US, and specifically Stanford University, affiliation of the most relevant authors in the field. HCPs analysis confirmed great interest in the study of the immune system and complex data processing in the mass cytometry research field.


Dietary Habits Related to Food Packaging and Population Exposure to PFASs.
Per- and polyfluoroalkyl substances (PFASs) are common industrial and consumer product chemicals with widespread human exposures that have been linked to adverse health effects. PFASs are commonly detected in foods and food-contact materials (FCMs), including fast food packaging and microwave popcorn bags. Our goal was to investigate associations between serum PFASs and consumption of restaurant food and popcorn in a representative sample of Americans. We analyzed 2003-2014 serum PFAS and dietary recall data from the National Health and Nutrition Examination Survey (NHANES). We used multivariable linear regressions to investigate relationships between consumption of fast food, restaurant food, food eaten at home, and microwave popcorn and serum levels of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS). Calories of food eaten at home in the past 24 h had significant inverse associations with serum levels of all five PFASs; these associations were stronger in women. Consumption of meals from fast food/pizza restaurants and other restaurants was generally associated with higher serum PFAS concentrations, based on 24-h and 7-d recall, with limited statistical significance. Consumption of popcorn was associated with significantly higher serum levels of PFOA, PFNA, PFDA, and PFOS, based on 24-h and 12-month recall, up to a 63% (95% CI: 34, 99) increase in PFDA among those who ate popcorn daily over the last 12 months. Associations between serum PFAS and popcorn consumption may be a consequence of PFAS migration from microwave popcorn bags. Inverse associations between serum PFAS and food eaten at home-primarily from grocery stores-is consistent with less contact between home-prepared food and FCMs, some of which contain PFASs. The potential for FCMs to contribute to PFAS exposure, coupled with concerns about toxicity and persistence, support the use of alternatives to PFASs in FCMs. https://doi.org/10.1289/EHP4092.


Discovery of potent 2,4-difluoro-linker poly(ADP-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy.
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, we identified a series of 2,4-difluorophenyl-linker analogs (15-55) derived from olaparib as novel PARP1 inhibitors. Four potent analogs 17, 43, 47, and 50 (IC50=2.2-4.4 nmol/L) effectively inhibited the proliferation of Chinese hamster lung fibroblast V-C8 cells (IC50=3.2-37.6 nmol/L) in vitro, and showed specificity toward BRCA-deficient cells (SI=40-510). The corresponding hydrochloride salts 56 and 57 (based on 43 and 47) were highly water soluble in pH=1.0 buffered salt solutions (1628.2 μg/mL, 2652.5 μg/mL). In a BRCA1-mutated xenograft model, oral administration of compound 56 (30 mg·kg-1·d-1, for 21 d) exhibited more prominent tumor growth inhibition (96.6%) compared with the same dose of olaparib (56.3%); in a BRCA2-mutated xenograft model, oral administration of analog 43 (10 mg·kg-1·d-1, for 28 d) significantly inhibited tumor growth (69.0%) and had no negative effects on the body weights. Additionally, compound 56 exhibited good oral bioavailability (F=32.2%), similar to that of olaparib (F=45.4%). Furthermore, the free base 43 of the hydrochloride salt 56 exhibited minimal hERG inhibition activity (IC50=6.64 μmol/L). Collectively, these data demonstrate that compound 56 may be an excellent drug candidate for the treatment of cancer, particularly BRCA-deficient tumors.


[Potassium channels and the development of new drugs].
Ion channel modulation has recently become an attractive target for experimental and clinical research in a never-ending quest for drug development. Following the decades of domination of calcium channel blockers, currently the focus is on potassium channels and their modulators; this is one of the most rapidly developing fields of research. Because potassium channels have an important role in maintaining the membrane potential in all tissues and in shaping the action potential in the heart, potassium channel modulators are expected to provide better therapies primarily in cardiology (acute coronary syndromes, arrhythmias) but also in other branches of medicine.


'Stuck' in nonstandard schedules? Married couples' nonstandard work schedules over the life course.
Though employment outside of regular daytime business hours has remained high since the 1990s, trends in nonstandard employment schedules over the life course and across households remain under-examined. The consequences of nonstandard scheduling extend to workers, their spouse, and children, urging greater attention to the distribution of nonstandard schedules at the couple-level. Using all three waves of the National Survey of Families and Households, this article examines the prevalence, persistence and sociodemographic patterns of rotating and night employment at the couple-level, following 913 married couples in the United States as they aged from the late 1980s to early 2000s. Though aging reduced the likelihood that couples had one or both spouses working nonstandard hours, roughly one-third of couples with nonstandard scheduling continued to experience nonstandard schedules during the subsequent observation period. Nonstandard schedules were stratified by education and race/ethnicity. This stratification persisted as couples aged, even after controlling for prior work schedules. Findings suggest that disadvantaged couples remain disproportionately exposed to schedules associated with negative outcomes for family well-being across the life course.


Multicenter stability of diffusion tensor imaging measures: a European clinical and physical phantom study.
Diffusion tensor imaging (DTI) detects white matter damage in neuro-psychiatric disorders, but data on reliability of DTI measures across more than two scanners are still missing. In this study we assessed multicenter reproducibility of DTI acquisitions based on a physical phantom as well as brain scans across 16 scanners. In addition, we performed DTI scans in a group of 26 patients with clinically probable Alzheimer's disease (AD) and 12 healthy elderly controls at one single center. We determined the variability of fractional anisotropy (FA) measures using manually placed regions of interest as well as automated tract based spatial statistics and deformation based analysis. The coefficient of variation (CV) of FA was 6.9% for the physical phantom data. The mean CV across the multicenter brain scans was 14% for tract based statistics, and 29% for deformation based analysis. The degree of variation was higher in less organized fiber tracts. Our findings suggest that a clinical and physical phantom study involving more than two scanners is indispensable to detect potential sources of bias and to reliably estimate effect size in multicenter diagnostic trials using DTI.


DFT study of the 1-octene metathesis reaction mechanism with WCl6/C catalytic system.
A catalytic system consisting of tungsten carbene generated from WCl(6) and an atomic carbon is investigated theoretically for the metathesis of 1-octene at B3LYP/extended LANL2DZ level of DFT. The ground-state geometries and charge distributions of the structures belonging to the reaction mechanism are located. Energetics for the complete set of reactions, involving the formation of the tungsten carbene precatalyst, Cl(4)WCCl(2), the formation of tungsten methylidene and tungsten heptylidene with this precatalyst, and finally productive and degenerative metathesis steps with these alkylidene species are calculated in terms of total electronic energy and thermal energies. The free-energy (ΔG(298)) surfaces of the structures involved in the related reactions are constructed. In addition, solvent effects on the single point energies of the structures are investigated for two different solvents, namely, cyclohexane and chloroform. The results indicate that the formation of the catalytically active heptylidene is energetically favored in comparison to the formation of methylidene, while the degenerative and productive metathesis steps are competitive. In the catalytic cycle, the formation of ethylene is exothermic, while the formation of 7-tetradecene is endothermic. As expected, solvent effects on the metathesis reactions are minor and solvation does not cause any change in the directions of the overall metathesis reactions.