Treating Child Disruptive Behavior in High-Risk Families: A Comparative Effectiveness Trial from a Community-Based Implementation.
Parent management training programs have proven the most effective way to treat child behavior problems. This study reports on an effectiveness trial of a community-based implementation of Parent-Child Interaction Therapy (PCIT) in comparison with the Dutch-developed Family Creative Therapy (FCT). Forty-five children (58 % boys) aged between 32 and 102 months (M = 67.7, SD = 15.9) were referred for treatment, and they and their parent(s) were randomly assigned to PCIT or FCT. Treatment effectiveness was measured primarily by the degree of improvement on child behavior problems, using the Eyberg Child Behavior Inventory. Secondary outcomes included parent and teacher report data and independent observations of parenting skills and child behavior. During the trial, randomization was violated by treatment crossovers (from FCT to PCIT). Intention-to-treat analyzes revealed no significant differences in the primary outcome at 6-month follow-up, but interpretation was hampered by the crossovers. Subsequent treatment-received analyzes revealed significant interaction effects between time and treatment condition, with greater improvements in child behavior and parenting skills for PCIT families compared to FCT families. Analyzes on families that fully completed the PCIT protocol also showed higher treatment maintenance at follow-up. The treatment-received analyzes indicated promising results for the effectiveness of PCIT in treating young children's disruptive behavior problems in a high-risk population. However, caution in generalizing the conclusions is needed in view of the design difficulties in this study. Suggestions are made for enhancing treatment delivery in daily practice, and clinical implications are noted.


Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial.
Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. clinicaltrials.gov Identifier: NCT00976521.


[Characterization of the epithelial sodium channel in human pre-eclampsia syncytiotrophoblast].
The syncytiotrophoblast (SCT), a multinucleated epithelium forming the outer layer of chorionic villi, acts in human placenta as a transporting barrier regulating the transference of nutrients, solutes and water between maternal and fetal blood. Electrolyte homeostasis and extracellular fluid volume are maintained primarily by regulated Na+ transport. The present study was conducted to analyze the presence of the epithelial Na channel (ENaC) in placental tissue from normal and pre-eclamptic women and in BeWo cell, a model of a human SCT. Changes in the expression of these proteins during sodium transport across the placenta may be related to the pathogeny of pre-eclampsia. The role that ENaC and Na+ transport deregulation play on human placental tissues still remains unknown although in aldosterone-responsive epithelial cells (kidney, colon), abnormalities upregulating its activity lead to increased Na+ uptake and hypertension (i.e. Liddle's syndrome) whereas a diminished channel activity can result in the pseudohypoaldosteronisn syndrome with salt loss and hypotension. Our results show that ENaC is expressed in the apical membrane of normal syncytiotrophoblast. The amplified fragment of alpha-ENaC was cloned and sequenced having a 100% identity with the sequence of (alpha-ENaC obtained from GenBank (SCNN1A, accession number Z92981). We found that the transcription of the alpha-ENaC mRNA was not detectable in preeclamptic placentas and the protein was not observed with immunohistochemistry staining, probably indicating a low protein expression level. In BeWo cells ENac was found and its expression is regulated by aldosterone, vasopressin, progesterone and estradiol. With patch clamp techniques we studied the currents trough ENaO channels in Bewo cells. We observed currents that were blocked by 10 microM amiloride in cells incubated in 100 nM aldosterone for 12 hs. The amplitude of this current was 20-fold the basal current, a reversal potential of 3 mV and a conductance of 127 +/- 26 pS/pF with pulses between -60 and -140 mV. These characteristics are similar to those reported in ENaC channels in several tissues. Although their roles in placenta are still poorly understood, the differences in the expression of ENaC in pre-eclamptic placentas may have consequences for ion transport and these data could lead to future studies concerning the mechanism involved in the pathophysiology of pre-eclampsia.


[Endovascular treatment of spinal dorsal intradural arteriovenous fistulas].
The dorsal spinal intradural arteriovenous fistulas (DSIAF) are infrequent and complex injuries are underdiagnosed condition and disability. The aim is to present our experience in the endovascular management. A retrospective and prospective study of patients with DSIAF treated by endovascular therapy (EVT) with n-butyl-cyanoacrylate during the period 2007-2013. 15 patients, 12 men and 3 women, mean age 37 years, were included. In 12 cases, the presentation was progressive and insidious over a period between 6 months and one year, while 3 had bleeding. The lesion in the thoracic location had 73 % of cases, lumbar 20 % and cervical 7 %. Prior to treatment observed disability grades 5 and 4 in 73 %, and 67 % had micturition disturbances. Complications grade 3, only one patient had transient deterioration of alert 6 hours after the procedure. Improvement to grades 1 and 2 disability at 48 hours, 3 and 6 months, 53 %, 73 % and 87 % respectively was found. EVT has a short operating time, bleeding volume is very low and the hospital stay is short compared with other surgical techniques. EVT is a safe and significant effectiveness in treating DSIAF procedure. This is the first series of cases treated with EVT in Mexico.


Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction.
To assess whether, in a cohort of patients with a small-for-gestational-age (SGA) fetus with estimated fetal weight ≤ 10th percentile, maternal hemodynamics, fetal biometry and Doppler indices at presentation can predict the subsequent development of an abnormal fetal Doppler index or delivery of a baby with birth weight < 3rd percentile. This was a prospective observational cohort study conducted at a specialist clinic for the management of pregnancies with a SGA fetus at King's College Hospital, London, UK. The study population comprised 86 singleton pregnancies with a SGA fetus, presenting at a median gestational age of 32 (range, 26-35) weeks. We measured maternal cardiac function using a non-invasive transthoracic bioreactance monitor, as well as mean arterial pressure, fetal biometry, and umbilical artery (UA), fetal middle cerebral artery (MCA) and uterine artery (UtA) pulsatility indices (PI), and the deepest vertical pool of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between pregnancies with evidence of an abnormal fetal Doppler index at presentation (Group 1), those that had developed an abnormal Doppler index at a subsequent visit (Group 2) and those that did not develop an abnormal Doppler index throughout pregnancy (Group 3). Abnormal fetal Doppler was defined as UA-PI > 95th percentile and/or MCA-PI < 5th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birth weight < 3rd percentile and those delivering a baby with birth weight ≥ 3rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birth weight < 3rd percentile and evolution from normal to abnormal fetal Doppler. In the study population, 14 (16%) cases were in Group 1, 19 (22%) in Group 2 and 53 (62%) in Group 3. Birth weight was < 3rd percentile in 39 (45%) cases and ≥ 3rd percentile in 47 (55%). There was decreased cardiac output and stroke volume and increased peripheral vascular resistance compared with a normal population, and the deviations from normal were most marked in Group 1. Pregnancies with birth weight < 3rd percentile, compared with those with birth weight ≥ 3rd percentile, had greater deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate, peripheral vascular resistance and UtA-PI. Multivariate logistic regression analysis demonstrated that, in the prediction of birth weight < 3rd percentile, maternal hemodynamic profile provided significant improvement to the prediction provided by maternal demographics, fetal biometry, UtA-PI, UA-PI and MCA-PI (difference between areas under receiver-operating characteristics curves, 0.18 (95% CI, 0.06-0.29); P = 0.002). In contrast, there was no significant independent contribution from maternal hemodynamics in the prediction of the subsequent development of abnormal fetal Doppler. In pregnancies with a SGA fetus, there is decreased maternal cardiac output and stroke volume and increased peripheral vascular resistance, and the deviations from normal are most marked in cases of redistribution in the fetal circulation and reduced amniotic fluid volume. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Effects of propofol on intracellular Ca2+ homeostasis in human astrocytoma cells.
The effects of propofol, a short-acting general anesthetic, upon cell growth and Ca(2+) signaling in a human astrocytic cell line were examined. Exposure of cells to graded concentrations of propofol resulted in a dose-dependent decrease in cell number with an inhibitory concentration of cell viability (IC50) of 31.7+/-1.2 microM. To evaluate the changes in intracellular Ca(2+) homeostasis induced by propofol, cytoplasmic and mitochondrial Ca(2+) were measured by fluorescence imaging. Mitochondrial Ca(2+) increased while cytoplasmic Ca(2+) decreased significantly at a propofol concentration lower than the IC50 (10 microM for 24 h, 1 microM for 72 h). In addition, propofol diminished the Ca(2+) response induced by fetal bovine serum (FBS). To determine the source of Ca(2+) alterations induced by propofol, pharmacologic agents targeting intracellular Ca(2+) homeostasis mechanisms were used. Nifedipine, an L-type Ca(2+) channel blocker, decreased FBS-induced Ca(2+) response of control cells to a level similar to propofol treated cells. However, diazoxide (a K(+)-ATP channel opener) administered 1 h before FBS addition restored the FBS response in propofol treated cells to a level similar to control. In addition, diazoxide increased mitochondrial Ca(2+) in control cells to a level comparable to propofol treated cells suggesting activation of these channels by propofol treatment. Addition of 1 muM RU-360 (a selective blocker of the mitochondrial Ca(2+) uniporter) for 30 min prior to propofol treatment restored mitochondrial and cytoplasmic Ca(2+) to control levels. These data suggest that voltage operated Ca(2+) channels, mitochondrial Ca(2+) and K(+)-ATP channels may be targets of propofol action in astrocytes.


Leucyl transfer RNA synthetase changes during soybean cotyledon senescence.
Previous work has shown the complement of leucyl transfer RNA (tRNA(Leu)) isoaccepting species present in soybean cotyledons to change during cotyledon senescence. Of the six tRNA(Leu) species resolved by Freon-column chromatography, the capacity of species 1-4 to accept leucine is decreased between 5 and 21 days of age. Parallel changes in tRNA(Leu) synthetase activity are reported here during the same time period. There is a reduction in the capacity of the synthetase from 21-day-old cotyledons to aminoacylate tRNA(Leu) 1-4, while the capacity to charge tRNA(Leu) 5-6 remains high. When tRNA(Leu) derived from 5-day-old cotyledons is maximally charged with the 21-day synthetase, the subsequent addition of synthetase from 5-day-old cotyledons promotes additional charging, primarily of species 1-4. These results suggest the presence of tRNA(Leu) "subspecies" within the individual peaks resolved on a Freon column, differing in synthetase specificity.


Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: alterations in the activities and protein expression of glutathione-related enzymes.
Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence in autism suggests a deficit in glutathione (GSH), a major endogenous antioxidant. It is not known whether the synthesis, consumption, and/or regeneration of GSH is affected in autism. In the cerebellum tissues from autism (n=10) and age-matched control subjects (n=10), the activities of GSH-related enzymes glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), and glutamate cysteine ligase (GCL) involved in antioxidant defense, detoxification, GSH regeneration, and synthesis, respectively, were analyzed. GCL is a rate-limiting enzyme for GSH synthesis, and the relationship between its activity and the protein expression of its catalytic subunit GCLC and its modulatory subunit GCLM was also compared between the autistic and the control groups. Results showed that the activities of GPx and GST were significantly decreased in autism compared to that of the control group (P<0.05). Although there was no significant difference in GR activity between autism and control groups, 40% of autistic subjects showed lower GR activity than 95% confidence interval (CI) of the control group. GCL activity was also significantly reduced by 38.7% in the autistic group compared to the control group (P=0.023), and 8 of 10 autistic subjects had values below 95% CI of the control group. The ratio of protein levels of GCLC to GCLM in the autism group was significantly higher than that of the control group (P=0.022), and GCLM protein levels were reduced by 37.3% in the autistic group compared to the control group. A positive strong correlation was observed between GCL activity and protein levels of GCLM (r=0.887) and GCLC (r=0.799) subunits in control subjects but not in autistic subjects, suggesting that regulation of GCL activity is affected in autism. These results suggest that enzymes involved in GSH homeostasis have impaired activities in the cerebellum in autism, and lower GCL activity in autism may be related to decreased protein expression of GCLM.


Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron.
The Ssy1-Ptr3-Ssy5 (SPS)-sensing pathway enables yeast to respond to extracellular amino acids. Stp1, the effector transcription factor, is synthesized as a latent cytoplasmic precursor with an N-terminal regulatory domain that restricts its nuclear accumulation. The negative regulatory mechanisms impinging on the N-terminal domain are poorly understood. However, Stp1 latency depends on three inner nuclear membrane proteins, Asi1, Asi2, and Asi3. We report that the N-terminal domain of Stp1 contains a small motif, designated RI, that fully accounts for latency. RI is modular, mediates interactions with the plasma membrane, and can retain histone Htb2 in the cytoplasm. A novel class of STP1 mutations affecting RI were isolated that are less efficiently retained in the cytoplasm but remain under tight negative control by the Asi proteins. Intriguingly, these mutant proteins exhibit enhanced stability in strains lacking ASI1. Our results indicate that RI mediates latency by two distinct activities: it functions as a cytoplasmic retention determinant and an Asi-dependent degron. These findings provide novel insights into the SPS-sensing pathway and demonstrate for the first time that the inner nuclear membrane Asi proteins function in a degradation pathway in the nucleus.


Concentric regulatory zones failed to halt surging COVID-19: Brooklyn 2020.
We relied on reports of confirmed case incidence and test positivity, along with data on the movements of devices with location-tracking software, to evaluate a novel scheme of three concentric regulatory zones introduced by then New York Governor Cuomo to address an outbreak of COVID-19 in South Brooklyn in the fall of 2020. The regulatory scheme imposed differential controls on access to eating places, schools, houses of worship, large gatherings and other businesses within the three zones, but without restrictions on mobility. Within the central red zone, COVID-19 incidence temporarily declined from 131.2 per 100,000 population during the week ending October 3 to 62.5 per 100,000 by the week ending October 31, but then rebounded to 153.6 per 100,000 by the week ending November 28. Within the intermediate orange and peripheral yellow zones combined, incidence steadily rose from 28.8 per 100,000 during the week ending October 3 to 109.9 per 100,000 by the week ending November 28. Data on device visits to pairs of eating establishments straddling the red-orange boundary confirmed compliance with access controls. More general analysis of device movements showed stable patterns of movement between and beyond zones unaffected by the Governor's orders. A geospatial regression model of COVID-19 incidence in relation to device movements across zip code tabulation areas identified a cluster of five high-movement ZCTAs with estimated reproduction number 1.91 (95% confidence interval, 1.27-2.55). In the highly populous area of South Brooklyn, controls on access alone, without restrictions on movement, were inadequate to halt an advancing COVID-19 outbreak.


A polarized view on DNA under tension.
In the past decades, sensitive fluorescence microscopy techniques have contributed significantly to our understanding of the dynamics of DNA. The specific labeling of DNA using intercalating dyes has allowed for quantitative measurement of the thermal fluctuations the polymers undergo. On the other hand, recent advances in single-molecule manipulation techniques have unraveled the mechanical and elastic properties of this intricate polymer. Here, we have combined these two approaches to study the conformational dynamics of DNA under a wide range of tensions. Using polarized fluorescence microscopy in conjunction with optical-tweezers-based manipulation of YOYO-intercalated DNA, we controllably align the YOYO dyes using DNA tension, enabling us to disentangle the rapid dynamics of the dyes from that of the DNA itself. With unprecedented control of the DNA alignment, we resolve an inconsistency in reports about the tilted orientation of intercalated dyes. We find that intercalated dyes are on average oriented perpendicular to the long axis of the DNA, yet undergo fast dynamics on the time scale of absorption and fluorescence emission. In the overstretching transition of double-stranded DNA, we do not observe changes in orientation or orientational dynamics of the dyes. Only beyond the overstretching transition, a considerable depolarization is observed, presumably caused by an average tilting of the DNA base pairs. Our combined approach thus contributes to the elucidation of unique features of the molecular dynamics of DNA.


Long-term clinical and angiographic outcomes in patients with cervico-cranial dissections treated with stent placement: a meta-analysis of case series.
Limited clinical and angiographic data exists for patients with spontaneous or traumatic cervico-cranial dissections treated with stent placement. We reviewed clinical and angiographic data on consecutive patients admitted to our hospital with spontaneous, traumatic, and iatrogenic cervico-cranial dissections treated with stent placement to study immediate and long-term clinical and angiographic outcomes. Additional patients were identified using pertinent studies published between 1980 and 2009, using a search of the PubMed, Cochrane, and Ovid libraries. Post-procedure complications and clinical outcomes were documented. Angiographic abnormalities collected at follow-up included presence of in-stent restenosis or pseudoaneurysm. After applying our strict search criteria, four studies including our series were used in the meta-analysis, representing 46 patients (mean age [standard deviation] 47 ± 14 years; 24 [52%] male) treated with stent placement for dissection. Overall, 72 stents were placed to treat 28 spontaneous, 11 traumatic, and 7 iatrogenic dissection patients with 51 dissections, involving 51 vessels; with a mean pre-stent stenosis of 71 ± 26% and mean post-stent stenosis of 6 ± 15%. The immediate and follow-up post-procedure complication rates per stent placed was 8 (11%) and 8 (11%), respectively. Among the 36 patients who underwent follow-up angiography, in-stent restenosis or pseudoaneurysms were present in 3 (8%) and 2 (6%) patients, respectively. A high rate of sustained resolution of angiographic abnormalities during long-term follow-up was noted, with a low rate of new transient ischemic attack, ischemic stroke, or death, supporting the feasibility, safety, and effectiveness of endovascular stent reconstruction.


Kinetic evidence for protein complexes between thioredoxin and NADP-malate dehydrogenase and presence of a thioredoxin binding site at the N-terminus of the enzyme.
The kinetics of activation of NADP-malate dehydrogenase (MDH; EC 188.8.131.52) from soybean and spinach leaves by the chloroplast thioredoxins isolated from the same plants, by the corresponding storage forms of the soybean chloroplast thioredoxins from soybean seeds, and by the bacterial Escherichia coli thioredoxin have been studied. The Hill equation has been applied to evaluate the saturation kinetics. The observed variable thioredoxin saturation characteristics (Vmax 0.37-14.5 mumol NADPH min-1 mg enzyme-1; K0.5 0.15-1.33 microM; Hill coefficient h 0.90-3.04) indicate that the activation of NADP-MDH depends strongly on the individual thioredoxin used. Thus, thioredoxin action is not solely due to simple reductive activation of the NADP-MDH. Specific thioredoxin complex formation between thioredoxin and NADP-MDH must be included into the mechanism of the activation process. To study the regulatory consequences of the specific thioredoxin/NADP-MDH complexes we investigated the saturation kinetics of the substrates NADPH and oxaloacetate in presence of different concentrations of each individual thioredoxin species. The kinetic characteristics of the substrates (S0.5, Vmax, and Hill coefficients h) varied individually in response to the different thioredoxin species substantiating our model of thioredoxin/ NADP-MDH complex formation. Aminopeptidase-K-truncated pea NADP-MDH has been used to demonstrate that the N-terminal 37 amino residues are involved in providing a specific thioredoxin binding site. The fact that the versatile light-dependent regulation of numerous enzyme activities by only two thioredoxin species in chloroplasts cannot be accomplished without the formation of thioredoxin/target enzyme complexes is discussed in detail.


The Yo-Yo intermittent recovery test level 1 is reliable in young high-level soccer players.
The aim of the study was to investigate test reliability of the Yo-Yo intermittent recovery test level 1 (YYIR1) in 36 high-level youth soccer players, aged between 13 and 18 years. Players were divided into three age groups (U15, U17 and U19) and completed three YYIR1 in three consecutive weeks. Pairwise comparisons were used to investigate test reliability (for distances and heart rate responses) using technical error (TE), coefficient of variation (CV), intra-class correlation (ICC) and limits of agreement (LOA) with Bland-Altman plots. The mean YYIR1 distances for the U15, U17 and U19 groups were 2024 ± 470 m, 2404 ± 347 m and 2547 ± 337 m, respectively. The results revealed that the TEs varied between 74 and 172 m, CVs between 3.0 and 7.5%, and ICCs between 0.87 and 0.95 across all age groups for the YYIR1 distance. For heart rate responses, the TEs varied between 1 and 6 bpm, CVs between 0.7 and 4.8%, and ICCs between 0.73 and 0.97. The small ratio LOA revealed that any two YYIR1 performances in one week will not differ by more than 9 to 28% due to measurement error. In summary, the YYIR1 performance and the physiological responses have proven to be highly reliable in a sample of Belgian high-level youth soccer players, aged between 13 and 18 years. The demonstrated high level of intermittent endurance capacity in all age groups may be used for comparison of other prospective young soccer players.


A qualitative study of the perceived effectiveness of refugee services among consumers, providers, and interpreters.
This study explored the perceptions of accessibility and cultural effectiveness of refugee services in the northeast region of the United States from refugees, interpreters who work with refugees in accessing these services, and the providers of the refugee services. The study examined the perceptions of 51 refugees from 10 countries, five individual interviews with providers and 26 provider survey responses representing 31 different agencies, and four interviews from interpreters. Qualitative interviews were conducted using a semi-structured interview schedule, were audiotaped, and transcribed. Further data were collected through a survey. All data were analyzed using constant comparative analysis. Participants shared feelings of frustration that services seemed poorly coordinated among the agencies and that the agencies appeared ill-prepared for the unique experiences of separate refugee groups. The three perspectives of refugee service delivery, as a consumer, a provider, or an interpreter, shared the perception that there was not a mechanism for the different services to collaborate effectively with each other, to create a network of coordinated services that would enhance services while decreasing burdens on individual centers, nor was there a system to best prepare the centers for new refugees.


The PIP Peptide of INFLORESCENCE DEFICIENT IN ABSCISSION Enhances Populus Leaf and Elaeis guineensis Fruit Abscission.
The programmed loss of a plant organ is called abscission, which is an important cell separation process that occurs with different organs throughout the life of a plant. The use of floral organ abscission in Arabidopsis thaliana as a model has allowed greater understanding of the complexities of organ abscission, but whether the regulatory pathways are conserved throughout the plant kingdom and for all organ abscission types is unknown. One important pathway that has attracted much attention involves a peptide ligand-receptor signalling system that consists of the secreted peptide IDA (INFLORESCENCE DEFICIENT IN ABSCISSION) and at least two leucine-rich repeat (LRR) receptor-like kinases (RLK), HAESA (HAE) and HAESA-LIKE2 (HSL2). In the current study we examine the bioactive potential of IDA peptides in two different abscission processes, leaf abscission in Populus and ripe fruit abscission in oil palm, and find in both cases treatment with IDA peptides enhances cell separation and abscission of both organ types. Our results provide evidence to suggest that the IDA-HAE-HSL2 pathway is conserved and functions in these phylogenetically divergent dicot and monocot species during both leaf and fruit abscission, respectively.


Surgical Repair of Tetralogy of Fallot With Absent Pulmonary Valve: Favorable Long-Term Results.
Tetralogy of Fallot with absent pulmonary valve syndrome (ToF-APVS) is a rare variant of tetralogy, associated with severe pulmonary valve regurgitation and aneurysmal dilation of the pulmonary arteries (PAs). Reported outcomes after surgical corrections are limited to single center, older series and might not reflect the current outcome. We aim to use data from a national registry to evaluate short- and long-term outcomes after surgical repair of ToF-APVS, to serve for counselling and planning. All children undergoing ToF-APVS repair in the UK between 2002 and 2013 were included. Survival and freedom from reintervention were estimated using the Kaplan-Meier method, and univariable analysis was done using the Weibull regression model. A total of 98 children, 45% male, 10% with DiGeorge syndrome, median age of 213 days (1 day to 13 years) were included. Mortality at 30 days was 3.3%, higher for neonates (6.7% vs 2.7%, P = 0.4) and those on preoperative mechanical ventilatory support (16.7% vs 1.3%, P = 0.04). Survival was 92.1% and freedom from pulmonary valve or conduit replacement (PVR) 73.2% at 10 years. Neonates had worse survival (hazard ratio [HR] 6.2, P = 0.02), freedom from PVR (HR 4.5, P = 0.01), freedom from PAs arterioplasty (HR 6.6, P = 0.001), and overall freedom from any reintervention (HR 5.3, P < 0.001). Low weight at repair was associated with worse freedom from PVR (P = 0.02) and from PAs arterioplasty (P = 0.009), preoperative ventilatory support with increased mortality (P = 0.009), the presence of DiGeorge syndrome was associated with worse freedom from PVR (HR 4, P = 0.02). Surgical repair of ToF-APVS can be performed with low early and late mortality, with improving results even in those with preoperative mechanical ventilatory support. The need for right ventricular outflow tract reintervention, including on the PAs, is an expected issue in the long term for the majority of patients.


Reporting quality of practice guidelines on colorectal cancer: evaluation using the RIGHT reporting checklist.
Clinical practice guidelines are an essential tool for translating evidence into practice. Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist assists to guide the reporting in guidelines. We used RIGHT to assess the reporting completeness and quality of guidelines on colorectal cancer (CRC). We searched the electronic databases Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) from January 1st, 2018 to December 1st, 2020 for guidelines on CRC. Websites of guideline development organizations were also searched. Two investigators assessed the reporting quality of the included guidelines, and calculated the numbers of guidelines that were compliant with each RIGHT checklist item and the mean proportions of reported items for each of the seven RIGHT checklist domains. Twenty-seven colorectal guidelines were included. The proportions of reported items in each RIGHT domain were 71.0% for Basic information, 66.2% for Background, 45.9% for Evidence, 68.8% for Recommendations, 24.1% for Review and quality assurance, 33.3% for Funding and declaration and management of interests, and 40.7% for Other information. The reporting quality of colorectal guidelines was moderate. A systematic use of the RIGHT checklist during the development process could improve the reporting quality of guidelines in the future.


Training Characteristics of a World Championship 5000-m Finalist and Multiple Continental Record Holder Over the Year Leading to a World Championship Final.
Optimal training for endurance performance remains a debated topic. In this case study, the training of a world-class middle-/long-distance runner over a year's duration is presented. The training is analyzed via 2 methods to define training intensity distribution (TID) (1) by physiological zones and (2) by zones based on race pace. TID was analyzed over the full season, but also over the final 6, 12, and 26 weeks to allow for consideration of periodization/phases of season. The results of both methods are compared. Other training data measured include volume and number of sessions. The average weekly volume for the athlete was 145.8 (24.8) km·wk-1. TID by physiological analysis was polarized for the last 6 weeks of the season but was pyramidal when analyzed over the final 12, 26, and 52 weeks of the season. TID by race-pace analysis was pyramidal across all time points. The athlete finished 12th in the final of the World Championship 5000-m and made the semifinal of the 1500-m. He was ranked in the top 16 in the world for 1500, 5000, and 10,000 m. The results of this study demonstrate a potential flaw with recent work suggesting polarized training as the most effective means to improve endurance performance. Here, different analysis methods produced 2 different types of TID. A polarized distribution was only seen when analyzed by physiological approach, and only during the last 6 weeks of a 52-week season. Longer-term prospective studies relating performance and physiological changes are suggested.


Complete nucleotide sequence of insertion element IS4351 from Bacteroides fragilis.
The nucleotide sequence and genetic analyses of one of the directly repeated sequences flanking the macrolide-lincosamide-streptogramin B drug resistance determinant, ermF, from the Bacteroides fragilis R plasmid, pBF4, suggested that this region is an insertion sequence (IS) element. This 1,155-base-pair element contained partially matched (20 of 25 base pairs) terminal-inverted repeats, overlapping, anti-parallel open reading frames, and nine promoterlike sequences, including three that were oriented outward. Analysis of this sequence revealed no significant nucleotide homology to 13 other known IS elements. Inasmuch as Southern blot hybridization analysis detected homologous sequences in chromosomal DNA and its G+C content (42 mol%) was similar to that of B. fragilis, the data suggested that this element is of Bacteroides origin. Transposition promoted by this element was demonstrated in recA E. coli. Recombinants were recovered by selecting for the activation of a promoterless chloramphenicol resistance gene on the plasmid pDH5110 and were characterized by restriction endonuclease mapping and Southern blot hybridization. We propose that this IS element be designated IS4351.


Going global: novel histone modifications in the globular domain of H3.
Post-translational modifications (PTM) of histones are key regulators of chromatin function. New mass spectrometrical technologies have revealed that PTMs are not restricted to the histone tails, but can also be found in the globular domains, especially at the DNA-binding surface of the nucleosomes. Recent work on this new group of epigenetic marks showed that these modifications have not only the potential to alter the physical properties of the nucleosome, but may act as signals that regulate the recruitment of effector proteins to chromatin as well.


Posttraumatic hemicerebral infarction in a four-year-old girl.
Brain infarction after trauma is uncommon. Injury of the carotid and vertebrobasilar arteries can cause brain infarction due to occlusion of brain blood flow. Emergency medical service (EMS) brought a 4-year-old girl involved in a car accident to the emergency room. She had had seizure controlled by diazepam. She was unconscious and her Glasgow coma scale (GCS) score was eight. Early vital signs were stable. Her first brain CT scan showed a subdural hematoma (SDH). One day after admission to ICU, her GCS decreased to five; hence, a control brain CT was performed. The brain CT scan showed a brain infarction. Six days after admission, her status worsened and her GCS dropped to three and her pupils became dilated bilaterally and unresponsive to light; she was pronounced dead. We present an uncommon case of posttraumatic brain infarction and synchronous SDH.


A comparative study of diagnostic tests for the assessment of herd magnesium status in cattle.
In nine of ten pre-calving dairy herds we found that herd magnesium (Mg) status could be determined with 95% confidence by measurements of serum Mg (S-Mg), urinary Mg fractional clearance ratio (FCR) or creatinine corrected urinary Mg concentration (CUM) from 10 representative cows. Our findings support clinical impressions that FCR and CUM are more sensitive than S-Mg as predictors of a positive production response to Mg supplementation of dairy cows. The available clinical data is not adequately controlled and there is a need for controlled production-response trials to refine interpretation and to confirm the predictive value of these tests. Pending such trials we suggest that mean FCR >10% or CUM >1.0 mmol/l indicate that a positive response is likely. In seven lactating herds the act of milking was not associated with depression of S-Mg and we conclude that sampling cows immediately after milking Gould not result in spurious elevations of FCR. FCR and CUM show close correlation with each other but not with S-Mg.


Mindfulness-Based Interventions for Weight Loss and CVD Risk Management.
Obesity affects more than one-third of U.S. adults and is a major cause of preventable morbidity and mortality, primarily from cardiovascular disease. Traditional behavioral interventions for weight loss typically focus on diet and exercise habits and often give little attention to the role of stress and emotions in the initiation and maintenance of unhealthy behaviors, which may account for their modest results and considerable variability in outcomes. Stress eating and emotional eating are increasingly recognized as important targets of weight loss interventions. Mindfulness-based interventions were specifically developed to promote greater self-efficacy in coping with stress and negative emotions, and appear to be effective for a variety of conditions. In recent years researchers have begun to study mindfulness interventions for weight loss and CVD risk management. This review describes the rationale for the use of mindfulness in interventions for weight loss and CVD risk management, summarizes the research to date, and suggests priorities for future research.


Historical change in an elite profession-Class origins and grades among law graduates over 200 years.
This article explores the relationship between social class and educational achievement measured by grades among Norwegian law graduates over a span of 200 years. We argue that class inequalities may arise due to mechanisms favouring 'insiders', meaning students whose families have legal backgrounds. Alternatively, a broader category of students with origins in educated or elite families could also enjoy special advantages. Our results indicate that there were insignificant class inequalities in grades before the beginning of the 20th century, when they first appeared, and that class inequalities increased to some extent subsequently. Graduates with origins from families with legal backgrounds or origins in the cultural upper class tend to be awarded the highest grades and those with farming or working-class origins tend to be awarded the lowest grades. Inequalities according to class origin can be explained only to a limited extent by performance at secondary school. Unlike class origin, however, the impact of grades at secondary school appears to be highly stable over time. We ask whether mechanisms favouring legal 'insiders' may have become less important over time, whereas the impact of cultural capital may have increased.


Multifunctional Solar Evaporator with Adjustable Island Structure Improves Performance and Salt Discharge Capacity of Desalination.
Interfacial solar steam generation (ISSG) is the main method to get fresh water from seawater or wastewater. The balance between evaporation rate and salt resistance is still a major challenge for ISSG. Herein, a wood aerogel island solar evaporator (WAISE) with tunable surface structure and wettability by synthesizing poly(n-isopropylacrylamide)-modified multi-walled carbon nanotube photothermal layers. Compared to dense surface structure evaporators, interfacial moisture transport, thermal localization, and surface water vapor diffusion of WAISE are greatly promoted, and the evaporation rate of WAISE increased by 87.64%. WAISE allows for record performance of 200 h continuous operation in 20% NaCl solution without salt accumulation. In addition, the photo-thermal-electric device is developed based on WAISE with continuous water purification, power generation, and irrigation functions. This work provides a new direction for the development of multifunctional water purification systems.


Do neurologists and primary care physicians agree on the extent of specialty involvement of patients referred to neurologists?
Understanding the roles and responsibilities of physicians who manage mutual patients is important for assuring good patient care. Among physicians expressing a preference to involve a neurologist in the care of a patient, we evaluated agreement between neurologists and primary care physicians for the extent of specialty involvement in the evaluation and management of the patient, and the factors influencing those preferences. A self-administered survey containing 3 clinical scenarios was developed with the assistance of a multispecialty advisory board and mailed to a stratified probability sample of physicians. Six hundred and eight family physicians, 624 general internists, and 492 neurologists in 9 U.S. states. For each scenario, those respondents who preferred involvement of a specialist were asked about the preferred extent of that involvement: one-time consultation with and without test/medication ordering, consultation and limited follow-up, or taking over ongoing care of the specialty problem as long as it persists. Survey response rate was 60%. For all 3 scenarios, neurologists preferred a greater extent of specialty involvement compared to primary care physicians (all P <.05). Other physician and practice characteristic factors, including financial incentives, had lesser or no influence on the extent of specialty involvement preferred. The disagreement between primary care physicians and specialists regarding the preferred extent of specialist involvement in the care of patients with neurological conditions should raise serious concerns among health care providers, policy makers, and educators about whether mutual patient care is coordinated and appropriate.


Level of glucocorticoid receptors in male rat liver under stress.
The binding of dexamethasone and corticosterone by specific glucocorticoid cytoplasmic liver receptors has been studied in intact, adrenalectomized and stressed male Wistar rats. The dissociation constants measured for receptor-hormone complexes were 7.2 x 10(-9) M for dexamethasone and 5.0 x 10(-9) M for corticosterone. Under 48 hour immobilisation stress, the number of binding sites on a dexamethasone-binding receptor was found to diminish from 2.9 x 10(-13) mol/mg protein (for intact rats) to 0.8 x 10(-13) mol/mg protein (for stressed rats). The amount of binding sites on a transcortin-like receptor decreased from 10 x 10(-14) mol/mg protein (in the intact rats) to 2.8 x 10(-14) mol/mg protein (in the stressed ones). Thus above data indicated certain reduction in binding site number for dexamethasone and corticosterone on the specific cytoplasmic receptors of rat liver under immobilisation stress.


Selective Isolation of Multidrug-Resistant Pedobacter spp., Producers of Novel Antibacterial Peptides.
Twenty-eight multidrug-resistant bacterial strains closely related or identical to Pedobacter cryoconitis, Pedobacter lusitanus and Pedobacter steynii were isolated from soil samples by selection for multidrug-resistance. Approximately 3-30% of the selected isolates were identified as Pedobacter, whereas isolation without antibiotics did not yield any isolates of this genus. Next generation sequencing data showed Pedobacter to be on 69th place among the bacterial genera (0.32% of bacterial sequences). The Pedobacter isolates produced a wide array of novel compounds when screened by UHPLC-MS/MSMS, and hierarchical cluster analysis resulted in several distinct clusters of compounds produced by specific isolates of Pedobacter, and most of these compounds were found to be peptides. The Pedobacter strain UP508 produced isopedopeptins, whereas another set of strains produced pedopeptins, which both are known cyclic lipodepsipeptides produced by Pedobacter sp. Other Pedobacter strains produced analogous peptides with a sequence variation. Further strains of Pedobacter produced additional novel antibacterial cyclic lipopeptides (ca 800 or 1400 Da in size) and/or linear lipopeptides (ca 700-960 Da in size). A 16S rRNA phylogenetic tree for the Pedobacter isolates revealed several distinct clades and subclades of isolates. One of the subclades comprised isolates producing isopedopeptin analogs, but the isopedopeptin producing isolate UP508 was clearly placed on a separate branch. We suggest that the non-ribosomal peptide synthases producing pedopeptins, isopedopeptins, and the analogous peptides, may derive from a common ancestral non-ribosomal peptide synthase gene cluster, which may have been subjected to a mutation leading to changed specificity in one of the modules and then to a modular rearrangement leading to the changed sequence found in the isopedopeptins produced by isolate UP508.


Sinus floor elevation using an osteotome technique without grafting materials or membranes.
This retrospective study aimed to radiographically assess sinus floor remodeling after using a modified osteotome technique without graft materials or membranes. After pilot drilling, residual bone was fractured and raised with the schneiderian membrane to the final implant length using osteotomes. Self-tapping implants were placed, and restorations were placed 6 months later. Twenty-four patients were available for follow-up after a mean observation period of 17.6 +/- 8.4 months. The implant survival rate at that time was 100%. Bone filling around the implants was measured and compared with baseline digital radiographs. New bone formation was 86.3% +/- 22.1% mesially and 89.7% +/- 13.3% distally. In nine cases, digital volume tomography was used to verify regeneration. Within the limitations of this study, use of the schneiderian membrane led to considerable bone regeneration, and good clinical success was achieved despite the omission of graft materials.


Gender Differences in Affective and Evaluative Responses to Experimentally Induced Body Checking of Positively and Negatively Valenced Body Parts.
Body checking (BC) is defined as behavior aimed at gaining information on body shape, size, or weight. Besides its occurrence as a transdiagnostic symptom in eating disorders (EDs), BC is widespread in non-clinical populations. It is associated with body dissatisfaction and the development of body image disturbances and ED. Males and females differ in terms of body dissatisfaction and associated BC strategies. However, the question of a gender-related intensity of negative affect and state body satisfaction as reactions to BC remains open. Therefore, the present experimental study aimed to examine gender differences in affective and evaluative responses to BC. We tested n = 60 women and n = 60 men in a crossover design, implementing two experimental conditions and one control condition. In the negative body checking condition (NBC), participants received standardized instructions to check negatively valenced body parts. In the positive body checking condition (PBC), by contrast, participants were asked to check positively valenced body parts. The control condition (CBC) consisted of playing a computer game. Before and after checking of one's own body, participants rated negative body-related affect, i.e., guilt, shame, and disgust, and state body satisfaction. The results indicate that both NBC and PBC led to an increase in negative affect for men and women. Eating pathology predicted negative affect after checking in NBC for both genders. Men reported a significantly higher state body satisfaction in all conditions, whereas only women showed decreased body satisfaction in NBC. These findings suggest that BC of any body part (i.e., positively or negatively valenced) leads to increased negative affect for both genders. Eating pathology significantly influences the affective responses to BC for both genders. Changes in state body satisfaction, however, only occur in females. An explanation might be that men generally report higher body satisfaction, resulting in a more stable body image. Females and males with pathological eating behavior seem to be more vulnerable to changes in negative affect. As negative affect is equally increased after NBC and PBC for both genders, BC might play a central role in the maintenance of body image disturbances in males and females.


Fishing for Contact: Modeling Perivascular Glioma Invasion in the Zebrafish Brain.
Glioblastoma multiforme (GBM) is a highly invasive, central nervous system (CNS) cancer for which there is no cure. Invading tumor cells evade treatment, limiting the efficacy of the current standard of care regimen. Understanding the underlying invasive behaviors that support tumor growth may allow for generation of novel GBM therapies. Zebrafish (Danio rerio) are attractive for genetics and live imaging and have, in recent years, emerged as a model system suitable for cancer biology research. While other groups have studied CNS tumors using zebrafish, few have concentrated on the invasive behaviors supporting the development of these diseases. Previous studies demonstrated that one of the main mechanisms of GBM invasion is perivascular invasion, i.e., single tumor cell migration along blood vessels. Here, we characterize phenotypes, methodology, and potential therapeutic avenues for utilizing zebrafish to model perivascular GBM invasion. Using patient-derived xenolines or an adherent cell line, we demonstrate tumor expansion within the zebrafish brain. Within 24-h postintracranial injection, D54-MG-tdTomato glioma cells produce fingerlike projections along the zebrafish brain vasculature. As few as 25 GBM cells were sufficient to promote single cell vessel co-option. Of note, these tumor-vessel interactions are CNS specific and do not occur on pre-existing blood vessels when injected into the animal's peripheral tissue. Tumor-vessel interactions increase over time and can be pharmacologically disrupted through inhibition of Wnt signaling. Therefore, zebrafish serve as a favorable model system to study perivascular glioma invasion, one of the deadly characteristics that make GBM so difficult to treat.


Isolation of gene sets affected specifically by polyglutamine expression: implication of the TOR signaling pathway in neurodegeneration.
Transcriptional dysregulation as a result of sequestration of essential transcription factors into protein aggregates formed by polyglutamine (polyQ) expansions can lead to late-onset progressive neurodegeneration. DNA microarray analysis of Drosophila expressing polyQ in the compound eye over time revealed large numbers of transcriptional changes at the earliest stages of the disease including repression of the transient receptor potential calcium channels in a polyQ-induced cell death specific manner. While significant differences in expression profiles were found between the Drosophila compound eye and polyQ-sensitive neural cells, a number of possible key overlapping regulators were extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity, suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.


Comparative assessment expression of the inhibitor of growth 1 gene (ING1) in normal and neoplastic tissues.
Studies have indicated that the tumor suppressor p33(ING1b) (13q33-34) interact with p53. Moreover, the association of functional protein forms of each member of the p33(ING1b)/p53 complex is essential for optimum activity of p53. The present report describes the sequencing of cDNAs corresponding to the p33(ING1b) mRNAs in a series of normal and tumor cell lines, and the production of monoclonal antibodies (MAbs) reactive with p33(ING1b). These antibodies were subsequently used to analyze p33(ING1b) expression in normal and tumor cell lines and tissues. No evidence of mutation of p33(ING1b) was found in any of the 15 tumor cell lines cDNAs studied. Our investigation of a wide range of normal tissues have shown that expression of the nuclear epitope is highly ubiquitous, whereas expression of the cytoplasmic form could be detected in only 50% of tissues studied. Considering neoplastic tissues, loss of nuclear p33(ING1b) was observed in melanoma, seminoma, papillary thyroid carcinoma, ductal breast carcinoma, and acute lymphoblastic leukemia. As with normal tissue, cytoplasmic p33(ING1b) was more restricted, being observed in around 30% of neoplastic tissues, but in melanoma, papillary thyroid carcinoma, ductal breast carcinoma, there was increased detection of cytoplasmic p33(ING1b) associated with concomitant loss of nuclear expression. These results may suggest that at least in some tumors, loss of effective p33(ING1b) function may be achieved by translocation to the cytoplasm or failure of nuclear localization.


beta-Carbolines enhance shock-induced suppression of drinking in rats.
By using Vogel's method to test the anxiolytic action of benzodiazepines and reducing the intensity of the current delivered to the drinking tube, it is possible to distinguish the pharmacological activity of three types of ligands for the benzodiazepine recognition site. An anticonflict action typical of anxiolytic benzodiazepines, a proconflict action typical of many beta-carbolines, including FG 7142 (beta-carboline-3-carboxylic acid ethyl ester methyl amide), and an antagonistic action of the proconflict and anticonflict actions typical of RO 15-1788 (ethyl-8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-alpha]-[1, 4]-benzodiazepine-3-carboxylate) and CGS 8216 (2-phenylpyrazolo[4,3-c]quinolin-3-(5H)-one). Pentylenetetrazole, which causes convulsions by interacting with a subunit of the gamma-aminobutyric acid receptor that is different from the benzodiazepine recognition site, also induces a proconflict action that is antagonized by anxiolytic benzodiazepines but not by RO 15-1788.


A dirty dozen: twelve p-value misconceptions.
The P value is a measure of statistical evidence that appears in virtually all medical research papers. Its interpretation is made extraordinarily difficult because it is not part of any formal system of statistical inference. As a result, the P value's inferential meaning is widely and often wildly misconstrued, a fact that has been pointed out in innumerable papers and books appearing since at least the 1940s. This commentary reviews a dozen of these common misinterpretations and explains why each is wrong. It also reviews the possible consequences of these improper understandings or representations of its meaning. Finally, it contrasts the P value with its Bayesian counterpart, the Bayes' factor, which has virtually all of the desirable properties of an evidential measure that the P value lacks, most notably interpretability. The most serious consequence of this array of P-value misconceptions is the false belief that the probability of a conclusion being in error can be calculated from the data in a single experiment without reference to external evidence or the plausibility of the underlying mechanism.


Effects of the DASH diet and losartan on serum urate among adults with hypertension: Results of a randomized trial.
Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4-week losartan or placebo. Serum urate was measured at baseline and after each 4-week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference -0.05 mg/dL; 95%CI: -0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (-0.33 mg/dL; 95%CI: -0.87, 0.21; P-interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (-0.23 mg/dL; 95%CI: -0.40, -0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (-0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout.


[Localized Caroli's disease associated with mucosecreting papillary adenocarcinoma. Value of hepatic resection].
A new case of carcinoma arising in Caroli's disease in a 48-year old male patient is reported. Since dilatation of the bile ducts was localized to the left lobe, left hepatectomy was performed. Histological examination showed that the tumour was a papillary mucoid adenocarcinoma. There was no recurrence of cholangitis while the patient survived. This case and a review of the literature shows that left hepatectomy suppresses repeated attacks of cholangitis in patients with Caroli's disease restricted to the left lobe, and that the incidence of carcinoma in Caroli's disease is higher than was formerly believed, which should encourage early surgical treatment when the disease is localized in the left lobe.


Effect of seaweed feeding before calving on colostral IgA concentration in Japanese Black cows.
In this study, we investigated the effect of feeding seaweed to Japanese Black cows before calving on IgA concentrations in colostrum. Seven Japanese Black breeding cows were used as test animals, with three cows in the seaweed-fed group (seaweed group) and four in the seaweed-non-fed group (control group). Each cow was fed 6 kg of sudangrass hay and 2.5 kg of compound feed twice daily (09:00 a.m. and 04:00 p.m.) as basal diets. Both groups had free access to water. In the seaweed group, commercially available seaweed feed was fed from 2 months before calving until the day of calving. The seaweed of 150 g/head/day was added to the basal diet at the morning feeding. Colostrum collected immediately after calving was used to measure IgA concentrations by ELISA. The IgA concentration in colostrum was significantly higher in the seaweed group than in the control group (P < 0.05). This suggested that feeding seaweed to Japanese Black cows before calving may increase IgA concentration in colostrum.


A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome-Intestine-Pancreas Axis.
The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.


Quantitative viability detection for a single microalgae cell by two-level photoexcitation.
A novel method for quantitative detection of the viability of a single microalgae cell by two-level photoexcitation is proposed in this paper. This method overcomes the difficulty of traditional methods in determining the cell viability by a fixed standard under a single photoexcitation. It is experimentally confirmed that this method is not limited by the species, morphology, size and structure of microalgae cells. An evaluation criterion of universal applicability is presented for the assessment of cell viability based on the large amount of experimental data. To the best of our knowledge, this is the first time that the relative fluorescence yield ratio Fr has been used to characterize the viability of single microalgae cells during cell migration. By using the relative fluorescence yield ratio, this method does not require the intensity of the excitation light to be very low for the assessment of the fluorescence yield of a dark-adapted microalgae cell, nor to be very strong to reach the saturated light level to assess the maximum fluorescence yield. Therefore, this method greatly reduces the technical difficulties of developing a sensor device. Well balanced portability, accuracy and universal applicability make it suitable for on-site real-time detection.


The properties of potato (Solanum tuberosum) lectin after deglycosylation by trifluoromethanesulphonic acid.
Potato (Solanum tuberosum) lectin, which is a very highly glycosylated glycoprotein, has been completely deglycosylated by use of the trifluoromethanesulphonic acid reagent described by Edge, Faltnek, Hof, Reichert & Weber [(1981) Analyt. Biochem. 118, 131-137]. This shows that both hydroxyproline-arabinofuranoside and serine-galactopyranoside linkages are hydrolysed. The deglycosylated lectin is still functional and cross-reacts with one component of an anti-(potato lectin) antiserum.


Peroxisome proliferator-activated receptor-gamma ligands inhibit choroidal neovascularization.
To determine the antiangiogenic effects of peroxisome proliferator-activated receptor (PPAR)-gamma agonists on ocular cells involved in the pathogenesis of choroidal neovascularization (CNV) in vitro and on experimental laser photocoagulation-induced CNV in vivo. PPAR-gamma expression in human retinal pigment epithelial (RPE) cells and bovine choroidal endothelial cells (CECs) was determined using an RNase protection assay and Western blot analysis. Two PPAR-gamma ligands, troglitazone (TRO) and rosiglitazone (RSG; 0.1-20 microM), were used to assess effects on RPE and CEC proliferation and migration and CEC tube formation in response to vascular endothelial growth factor (VEGF). The effects of intravitreal injection of TRO on laser photocoagulation-induced CNV lesions in rat eyes (15 experimental, 15 control, nine burns per eye) and cynomolgus monkey eyes (two experimental, two control, seven paramacular burns per eye) was assessed by fluorescein angiography and histologic evaluation. RESULTS. PPAR-gamma1 was expressed in both RPE and CEC. PPAR-gamma ligands significantly inhibited VEGF-induced migration and proliferation in both cell types and tube formation of CEC in a dose-response manner. CNV in rats was markedly inhibited by intravitreous injection of TRO (P < 0.001). Lesions showed significantly less fluorescein leakage and were histologically thinner in the TRO-treated animals. Similar findings were present in the TRO-treated lesions in two monkey eyes. The drug showed no apparent adverse effects in the adjacent retina or in control eyes. The inhibition of VEGF-induced choroidal angiogenesis in vitro, and CNV in vivo by PPAR-gamma ligands suggests the potential application of these agents in the large group of patients with age-related macular degeneration complicated by CNV.


Evidence-based approach to HIV/AIDS policy and research prioritization in the Islamic Republic of Iran.
In formulating the second national strategic plan for prevention of HIV/AIDS in the Islamic Republic of Iran a more evidence-based approach was needed. This paper reports on a systematic review of the local evidence about the determinants of HIV/AIDS transmission in 3 categories: poor knowledge and negative attitudes about HIV transmission; injection drug use; and sexual promiscuity. Of 93 reports reviewed, 53 met the inclusion criteria. Information about the prevalence and magnitude of effect for the 3 risk determinants at the national and regional level was scarce. Heterogeneity between studies, even in the same sub-population, was significant. An improved research base and better sharing of information are needed within countries of the Eastern Mediterranean Region.


Evidence maps: communicating risk assessments in societal controversies: the case of engineered nanoparticles.
The transparent and fair characterization of scientific evidence for reporting the results of a hazard assessment is a demanding task. In this article, we present an approach for characterizing evidence--the evidence map approach. The theoretical starting point is to view evidence characterization as a form of argumentation. Thus, evidence maps are designed to depict the evidence base, the pro and con arguments, and the remaining uncertainties, which together lead experts to their conclusions when summarizing and evaluating the scientific evidence about a potential hazard. To illustrate its use, the evidence maps approach is applied to characterizing the health-relevant effects of engineered nanoparticles. Empirical data from an online survey suggests that the use of evidence maps improves the reporting of hazard assessments. Nonexperts prefer to receive the information included in an evidence map in order to come to an informed judgment. Furthermore, the benefits and limitations of evidence maps are discussed in the light of recent literature on risk communication. Finally, the article underlines the need for further research in order to increase quality of evidence reporting.


Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2.
Emerging evidence suggests that restoration of blood flow in a stuttering manner may limit lethal myocardial ischemia-reperfusion injury. However, the mechanisms contributing to this phenomenon, termed postconditioning (post-C), remain poorly defined. Our aim was to test the hypothesis that activation of classic "survival kinases," phosphatidylinositol 3-kinase (PI3-kinase) and/or extracellular signal-regulated kinase (ERK)1/2, may play a role in post-C-induced cardioprotection. In protocol 1, isolated buffer-perfused rabbit hearts underwent 30 min of sustained coronary artery occlusion and were randomized to receive abrupt reperfusion (controls) or four cycles of 30 s of reperfusion and 30 s of reocclusion before full restoration of flow (post-C). Protocol 2 was identical except control and postconditioned hearts received the PI3-kinase inhibitor LY-294002 (protocol 2A) or the ERK1/2 antagonist PD-98059 (protocol 2B) throughout the first 25 min of reperfusion, whereas in protocol 3, myocardial samples were obtained during the early minutes of reflow from additional control, postconditioned, and nonischemic sham hearts for the assessment, by standard immunoblotting, of phospho-Akt (downstream target of PI3-kinase) and phospho-ERK. Protocols 1 and 2 corroborated that infarct size (delineated by tetrazolium staining and expressed as a percent of risk region) was reduced in postconditioned hearts vs. control hearts and also revealed that post-C-induced cardioprotection was maintained despite LY-294002 treatment but was abrogated by PD-98059. These pharmacological data were supported by protocol 3, which showed increased immunoreactivity of phospho-ERK but not phospho-Akt with post-C. Thus our results implicate the involvement of ERK1/2 rather than PI3-kinase/Akt in the reduction of infarct size achieved with post-C.


The diagnosis and treatment of abduction deficiencies.
Deficient abduction can be due to both innervational deficiencies and/or mechanical restrictions. Innervational deficiencies include lateral rectus weakness or paralysis, myasthenia gravis, progressive external ophthalmoplegia nd Duane's syndrome with aberrant innervation to the lateral rectus muscle. Mechanical causes include restrictions on the medial side of the globe (a tight medical rectus due to endocrine ophthalmopathy, a contractured medial rectus muscle as a result of a lateral rectus paralysis, excessive resection of the medial rectus muscle, scarring and hemorrhage due to multiple previous operations upon the medial rectus), as well as a posteriorly inserted lateral rectus. This latter condition may result from a traumatically disinserted lateral rectus muscle, an excessively recessed lateral rectus muscle or a lateral rectus that has slipped from its attachment following strabismus surgery. Insufficient force for full abduction is caused by posterior insertion of the lateral rectus. The diagnosis of these various conditions is considered with reference to the forced duction, force generation and saccadic velocity tests. The treatment of these different causes of abduction deficiency is discussed noting that the approach to treatment depends upon the etiology of the abduction deficiency.


Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study.
The lipid profile is consistently associated with coronary artery disease (CAD) and ischemic stroke (IS). However, the lipoprotein subfractions have not been deeply explored in stroke subtypes, especially in IS outcome. We performed two-sample Mendelian randomization (MR) analysis using 92 lipid traits measured by nuclear magnetic resonance in 115,000 subjects from the UK Biobank. Data for genetic associations with IS, its subtypes, and long-term outcome (LTO) were obtained from three cohorts of European ancestry: GIGASTROKE (73,652 cases, 1,234,808 controls), GODS (n = 1791) and GISCOME (n = 6165). Results obtained using CARDIoGRAMPlusC4D were used to identify differences with CAD. Genetically determined low concentration of medium high-density lipoprotein (HDL) particles (odds ratio (OR) = 0.92, 95% CI 0.88-0.96; p = 3.6 × 10-4) and its cholesterol content (OR = 0.92, 95% CI 0.88-0.96; p = 1.9 × 10-4) showed causal associations with an increased risk of stroke. Genetic predisposition to high apolipoprotein (apo)B to apoA-I ratio was causally associated with an increased risk of IS (OR = 1.12, 95% CI 1.06-1.18, p = 1.1 × 10-4), and a highly suggestive association was found between non-esterified cholesterol in low-density lipoprotein (LDL) and increased risk of atherothrombotic stroke (LAS) (OR = 1.35, 95% CI 1.10-1.66; p = 4.0 × 10-3). Low cholesterol in small and medium LDL was suggestively associated with poor LTO. Our results support that low medium HDL concentration was causally associated with an increased stroke risk, while high levels of non-esterified cholesterol in LDL were suggestively associated with an increased risk of LAS and with a better LTO.


Haematopoietic transplant potential of unrelated and related cord blood: the first six years of the EUROCORD/NETCORD Bank Germany.
To date, human umbilical cord blood (CB) has been employed successfully in well over 1000 allogeneic (unrelated and sibling) stem cell transplantations. Because of primary limitations in volume and cell numbers, over 90% of these transplantations were performed in children. Therefore requests for well standardised cord blood units of high quality are now increasing constantly. Examination and standardisation of unrelated and related cord blood stem cell preparations and banking as well as their biological characterisation was already initiated in Düsseldorf in 1992. Hitherto a total of 3236 CB samples with a mean volume of 89 +/- 25 ml, a mean total number of nucleated cells (NC) of 10 +/- 5 x 10(8) and a mean number of CFU-GM of 6 +/- 5 x 10(5) have also been validated by haematological, immunological and microbiological criteria. In addition to that, 97 directed CB donations of siblings with a clinical indication have been characterised and banked along the same lines. All CB units were collected from the umbilical cord vein immediately after vaginal full term delivery or caesarean section, then frozen and stored in liquid nitrogen. 1940 CB units were stored unseparated, the other 1296 were volume reduced using Hetastarch (HES) with a mean recovery of 85 +/- 13% of the nucleated cells, 86 +/- 12% and 84 +/- 13% for CFC and CD34+ cells, respectively. Only 5.0 ml of a CB sample is required for routine laboratory testing as there are HLA-class I typing, HLA-class II typing by sequence specific oligonucleotide probes (PCR-SOP), ABO typing, sterility control, assessment of progenitor and stem cells by colony forming assays, and CD34+ status as well as certain viral infections such as CMV, Hepatitis B, C, HIV, Parvo B19 by PCR technology before releasing the CB unit for transplantation. For apparent viral infections, maternal sera obtained at birth were tested for HBsAg, anti-HBc, anti-HCV, -HAV-(IgG, IgM), -HIV-1-2, -EBV- (IgG, IgM), -HTLVI-II, -CMV (IgM, IgG), toxoplasmosis and syphilis. Within the last three years a total of 4860 preliminary searches and 680 extended unit reports were submitted to the CB bank Düsseldorf by fax or World Wide Web. So far 68 unrelated and 3 related CB units were delivered. From these 70 have been transplanted in 30 different transplant centres world-wide. Until now the evaluation of the first 53 unrelated CB-transplantations was performed together with the EUROCORD transplant registry. Three patients were excluded from the analysis, since they received an unrelated CB-transplant for non-engraftment after previous allotransplants. The median patient age of these 50 patients was 5.0 years (range 0.3-44), the median weight 18 kg (range 4-70 kg). The majority of the patients transplanted for malignancies (66%) suffered from ALL (n = 19), AML (n = 7), CML (n = 4) and lymphoma (n = 2) with two third (75%) in an intermediate (2nd CR) or advanced stage of disease (> 2nd CR); 13 patients had metabolic diseases and immunodeficiencies and three had aplastic anaemia. All CB samples as well as the patients' blood samples were typed in Düsseldorf for HLA-class I by serology confirmed by PCR-SSP and by high resolution DNA typing for HLA-DRB1 and HLA-DQB1 alleles. 96% of the 50 patients receiving unrelated CB were mismatched at one or more HLA-antigens. 41 of the 50 patients transplanted with unrelated CB from Düsseldorf were evaluable for engraftment with an overall engraftment rate of 83%. According to the defined criteria of EUROCORD, 9 of the 50 patients were not evaluable for engraftment, since they died before day 60. The present median follow-up time is 14 months (1.4-38). The Kaplan-Meier estimate of survival at one year is 42 percent. The three paediatric patients after sibling CB transplantations (ALL, amegakaryocytic thrombocytopenia and CML) are alive with a follow-up time of 350, 379 days and 531 days. (ABSTRACT TRUNCATED)


Molecular analysis of ciprofloxacin resistance mechanisms in Malaysian ESBL-producing Klebsiella pneumoniae isolates and development of mismatch amplification mutation assays (MAMA) for rapid detection of gyrA and parC mutations.
Ninety-three Malaysian extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolates were investigated for ciprofloxacin resistance. Two mismatch amplification mutation (MAMA) assays were developed and used to facilitate rapid detection of gyrA and parC mutations. The isolates were also screened for plasmid-mediated quinolone resistance (PMQR) genes including aac(6')-Ib-cr, qepA, and qnr. Ciprofloxacin resistance (MICs 4- ≥ 32 μ g/mL) was noted in 34 (37%) isolates, of which 33 isolates had multiple mutations either in gyrA alone (n = 1) or in both gyrA and parC regions (n = 32). aac(6')-Ib-cr was the most common PMQR gene detected in this study (n = 61), followed by qnrB and qnrS (n = 55 and 1, resp.). Low-level ciprofloxacin resistance (MICs 1-2 μ g/mL) was noted in 40 (43%) isolates carrying qnrB accompanied by either aac(6')-Ib-cr (n = 34) or a single gyrA 83 mutation (n = 6). Ciprofloxacin resistance was significantly associated with the presence of multiple mutations in gyrA and parC regions. While the isolates harbouring gyrA and/or parC alteration were distributed into 11 PFGE clusters, no specific clusters were associated with isolates carrying PMQR genes. The high prevalence of ciprofloxacin resistance amongst the Malaysian ESBL-producing K. pneumoniae isolates suggests the need for more effective infection control measures to limit the spread of these resistant organisms in the hospital.


Modulation of H2 histamine receptor-mediated cAMP generation and granulocytic differentiation by extracellular nucleotides via activation of protein kinase C.
Extracellular ATP exerts a variety of biological actions through several kinds of P2 receptor in HL-60 promyelocytes. We show that stimulation of P2Y2 receptors with ATP and analogs resulted in the inhibition of a subsequently histamine-induced cAMP production and functional differentiation. Treatment of the cells with phorbol 12-myristate 13-acetate also blocked the histamine-mediated cAMP generation just as ATP did. Incubation of the cells with the protein kinase C inhibitor bisindolylmaleimide (GF109203X) abolished the inhibitory effects of extracellular nucleotides, suggesting that protein kinase C may act as an inter-regulator between two receptors. However, ATP did not affect the binding affinity or total binding of [3H]histamine to membrane receptors; it also did not heterologously desensitize H2 receptors. The ATP treatment synergistically elevated the cAMP levels induced directly by forskolin or indirectly by G protein activation after cholera toxin treatment. This indicates that the site of the protein kinase C action is not the G protein or effector enzyme. Co-stimulation of the cells with nucleotides and histamine inhibited histamine-mediated granulocytic differentiation, which was evaluated by looking at the extent of N-formyl-methionyl-leucyl-phenylalanine responses. Taken together, the results demonstrate that extracellular nucleotides are negatively involved in the modulation of histamine signaling via activation of protein kinase C, probably by inhibiting coupling between receptor and G protein.


Time course and role of luteinizing hormone and follicle-stimulating hormone in the expansion of the Leydig cell population at the time of puberty in the rhesus monkey (Macaca mulatta).
In higher primates, development of the adult population of Leydig cells has received little attention. Here, the emergence of 3β-hydroxysteroid dehydrogenase (HSD3B) positive cells in the testis of the rhesus monkey was examined during spontaneous puberty, and correlated with S-phase labeling in the interstitium at this critical stage of development. In addition, the relative role of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in initiating the pubertal expansion of Leydig cells was studied by precociously stimulating the juvenile testis in vivo with pulsatile 11-day infusions of recombinant LH and FSH, either alone or in combination. At the time of castration, testes were immersion fixed in Bouin's, embedded in paraffin, and sectioned at 5 μm. Leydig cells/testis were enumerated using HSD3B as a Leydig cell marker. Leydig cell number per testis increased progressively during puberty to reach values in the adult approximately 10 fold greater than in early-pubertal animals. The rise in cell number was associated with an increase in nuclear diameter. That the pubertal expansion of Leydig cell number was driven primarily by the increase in LH secretion at this stage of development was suggested by the finding that precocious stimulation of mid-juvenile monkeys with LH, either alone or in combination with that of FSH, resulted in a 20-30 fold increase in the number of HSD3B-positive cells. Interestingly, precocious FSH stimulation, alone, also resulted in appearance of Leydig cells as indicated by the occasional HSD3B-positive cell in the interstitium. The nuclear diameter of these Leydig cells, however, was less than that of those generated in response to LH.


Lumbar vertebral angles and back muscle loading with belts.
The study examined belt effects on the change of lumbosacral angle (LSA) and back muscle activity in postures of standing, erect sitting, and slump sitting. We thought that the resulting changes of LSA and back muscle activity when wearing belts with different mechanical characteristics should be different. Eighteen healthy male subjects participated in this study. Though we failed to identify a significant belt effect on the back muscle EMG, the radiographic data revealed an interactive effect of postures and belts on the change of LSA. In standing, the belts increased LSA by increasing almost every lumbar vertebral angle. In erect sitting, the lumbar belt had no effect but the pelvic belt decreased LSA through a decrease in the L1/L3. While sitting slump with a trunk flexion of 15 degrees, both belts increased LSA by restricting the movement of the pelvis. Belt effect on LSA was accompanied with a change of pelvic angle. Significant correlation was found between the backward rotation angles of the pelvis and the angles of LSA (r = 0.692, p < 0.0001), also between the decrease of pelvic angles and the increase of back muscle EMG (r = -0.4, p = 0.017). A change in LSA and pelvic angle after wearing a belt along with posture change seems lead to an increase of the myoelectric activities on the back.


Management of acute exacerbations of COPD: a summary and appraisal of published evidence.
To critically review the available data on the diagnostic evaluation, risk stratification, and therapeutic management of patients with acute exacerbations of COPD. English-language articles were identified from the following databases: MEDLINE (from 1966 to week 5, 2000), EMBASE (from 1974 to week 18, 2000), HealthStar (from 1975 to June 2000), and the Cochrane Controlled Trials Register (2000, issue 1). The best available evidence on each subtopic then was selected for analysis. Randomized trials, sometimes buttressed by cohort studies, were used to evaluate therapeutic interventions. Cohort studies were used to evaluate diagnostic tests and risk stratification. Study design and results were summarized in evidence tables. Individual studies were rated as to their internal validity, external validity, and quality of study design. Statistical analyses of combined data were not performed. Limited data exist regarding the utility of most diagnostic tests. However, chest radiography and arterial blood gas sampling appear to be useful, while short-term spirometry measurements do not. In terms of the risk of relapse and the risk of death after hospitalization for an acute exacerbation, there are identifiable clinical variables that are associated with these outcomes. Therapies for which there is evidence of efficacy include bronchodilators, corticosteroids, and noninvasive positive-pressure ventilation. There is also support for the use of antibiotics in patients with more severe exacerbations. Based on limited data, mucolytics and chest physiotherapy do not appear to be of benefit, and oxygen supplementation appears to increase the risk of respiratory failure in an identifiable subgroup of patients. Although suggestions for appropriate management can be made based on available evidence, the supporting literature is spotty. Further high-quality research is needed and will require an improved, generally acceptable, and transportable definition of the syndrome "acute exacerbation of COPD" and improved methods for observing and measuring outcomes.


Data Exchange Interoperability in IoT Ecosystem for Smart Parking and EV Charging.
Many domains are trying to integrate with the Internet of Things (IoT) ecosystem, such as public administrations starting smart city initiatives all over the world. Cities are becoming smart in many ways: smart mobility, smart buildings, smart environment and so on. However, the problem of non-interoperability in the IoT hinders the seamless communication between all kinds of IoT devices. Different domain specific IoT applications use different interoperability standards. These standards are usually not interoperable with each other. IoT applications and ecosystems therefore tend to use a vertical communication model that does not allow data sharing horizontally across different IoT ecosystems. In 2014, The Open Group published two domain-independent IoT messaging standards, O-MI and O-DF, aiming to solve the interoperability problem. In this article we describe the practical use of O-MI/O-DF standards for reaching interoperability in a mobile application for the smart city context, in particular for the Smart Mobility domain, electric vehicle (EV) charging case study. The proof-of-concept of the smart EV charging ecosystem with mobile application user interface was developed as a part of an EU (Horizon 2020) Project bIoTope.


Evaluation of physician assistants in National Health Service Scotland.
Physician assistants (PAs) have medical training and work supervised by a doctor. In 2006-2008 the Scottish Government piloted use of USA-trained PAs. The aim of the paper is to evaluate the impact and contribution made by PAs to delivering effective health care in National Health Service (NHS) Scotland. Mixed methods, longitudinally, including interviews, feedback forms and activity data collection. Data analysis used nVivo, SPSS and Excel. Participants were 15 USA-trained PAs, medical supervisors and team members, 20 patients, four NHS senior managers and three trade union representatives. Settings were four Scottish NHS Boards where PAs worked in primary care, out of hours clinics, emergency medicine, intermediate care and orthopaedics. Two minor patient safety issues arose. Patients were satisfied with PAs. Scope of practice did not replicate US working. Inability to prescribe was a hindrance. PAs tended to have longer consultations, but provided continuity and an educational resource. They were assessed to be mid-level practitioners approximating to nurse practitioner or generalist doctor. Valued features were generalism, medical background, confidence differential diagnosis and communication. Interviewees suggested PAs could fulfil roles currently filled by medical staff, potentially saving resources. In conclusion, there is potential for PAs to fulfil distinctive mid-level roles in the Scottish NHS adding value in continuity, communication and medical approach.


The Combined Effect of Tropicamide and Phenylephrine on Corneal Astigmatism Axis.
To analyze astigmatism axis changes after tropicamide and phenylephrine combined instillation. One hundred and thirty-one eyes from 66 patients enrolled this cross-sectional study. An extensive ocular examination was carried out prior to tropicamide and phenylephrine instillation. Power and axis value from flat, steep, and mean keratometry were calculated using an Auto Kerato-Refractometer (AKR). Later, topography and tomography maps were evaluated with Pentacam HR® (Oculus, Wetzlar, Germany). Subsequently, a single drop of tropicamide 1% and phenylephrine hydrochloride 10% were instilled twice, with a five-minute gap between each instillation. After 30 minutes, the AKR and Pentacam HR® tests were repeated. Incyclotorsion was found in 59 eyes (45.1%) and mean absolute incyclotorsion change was 3.91 ± 3.62 degrees (0.10 to 14.20). Excyclotorsion was found in 72 eyes (54.9%) and mean excyclotorsion change was 4.99 ± 5.94 degrees (0.20 to 36.20). We observed that 74.6% and 68.1% of eyes experienced incyclotorsion and excyclotorsion within 0 to 5 degrees, respectively. Fewer patients experienced incyclotorsion and excyclotorsion changes within 5 to 10 degrees, precisely 11.8% and 19.4%, respectively. Eyes that experienced over 10 degrees of incyclotorsion and excyclotorsion were 13.6% and 12.5%, respectively. Astigmatism axis could change after combined tropicamide and phenylephrine instillation. Reference axis marking in astigmatism correction surgery should be performed under the same circumstances as the astigmatism axis has been measured.


Laser photocoagulation of feeder vessels in lipid keratopathy.
Argon laser photocoagulation was performed on rabbit eyes with lipid keratopathy. The lipid keratopathy was induced by rendering 30 rabbits hypercholesterolemic and inciting neovascularization by insertion of corneal sutures. The number of laser shots required to occlude corneal vessels increased with the suture residence time, whereas the number of limbal shots remained essentially constant. Corneal opacification and cholesterol content increased as a result of greater suture residence time and unexpectedly from the laser applications which were administered in a single treatment session.


Effects of neonatal lung abnormalities on parenchymal R2 * estimates.
Infants admitted to the neonatal intensive care unit (NICU) often suffer from multifaceted pulmonary morbidities that are not well understood. Ultrashort echo time (UTE) magnetic resonance imaging (MRI) is a promising technique for pulmonary imaging in this population without requiring exposure to ionizing radiation. The aims of this study were to investigate the effect of neonatal pulmonary disease on R2 * and tissue density and to utilize numerical simulations to evaluate the effect of different alveolar structures on predicted R2 *.This was a prospective study, in which 17 neonatal human subjects (five control, seven with bronchopulmonary dysplasia [BPD], five with congenital diaphragmatic hernia [CDH]) were enrolled. Twelve subjects were male and five were female, with postmenstrual age (PMA) at MRI of 39.7 ± 4.7 weeks. A 1.5T/multiecho three-dimensional UTE MRI was used. Pulmonary R2 * and tissue density were compared across disease groups over the whole lung and regionally. A spherical shell alveolar model was used to predict the expected R2 * over a range of tissue densities and tissue susceptibilities. Tests for significantly different mean R2 * and tissue densities across disease groups were evaluated using analysis of variance, with subsequent pairwise group comparisons performed using t tests. Lung tissue density was lower in the ipsilateral lung in CDH compared to both controls and BPD patients (both p < 0.05), while only the contralateral lung in CDH (CDHc) had higher whole-lung R2 * than both controls and BPD (both p < 0.05). R2 * differences were significant between controls and CDHc within all tissue density ranges (all p < 0.05) with the exception of the 80%-90% range (p = 0.17). Simulations predicted an inverse relationship between alveolar tissue density and R2 * that matches empirical human data. Alveolar wall thickness had no effect on R2 * independent of density (p = 1). The inverse relationship between R2 * and tissue density is influenced by the presence of disease globally and regionally in neonates with BPD and CDH in the NICU. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.


Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes.
Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown. In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events. Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome. Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729.).


Characterization of Osteogenesis and Chondrogenesis of Human Decellularized Allogeneic Bone with Mesenchymal Stem Cells Derived from Bone Marrow, Adipose Tissue, and Wharton's Jelly.
Allogeneic bone grafts are a promising material for bone implantation due to reduced operative trauma, reduced blood loss, and no donor-site morbidity. Although human decellularized allogeneic bone (hDCB) can be used to fill bone defects, the research of revitalizing hDCB blocks with human mesenchymal stem cells (hMSCs) for osteochondral regeneration is missing. The hMSCs derived from bone marrow, adipose tissue, and Wharton's jelly (BMMSCs, ADMSCs, and UMSCs, respectively) are potential candidates for bone regeneration. This study characterized the potential of hDCB as a scaffold for osteogenesis and chondrogenesis of BMMSCs, ADMSCs, and UMSCs. The pore sizes and mechanical strength of hDCB were characterized. Cell survival and adhesion of hMSCs were investigated using MTT assay and F-actin staining. Alizarin Red S and Safranin O staining were conducted to demonstrate calcium deposition and proteoglycan production of hMSCs after osteogenic and chondrogenic differentiation, respectively. A RT-qPCR was performed to analyze the expression levels of osteogenic and chondrogenic markers in hMSCs. Results indicated that BMMSCs and ADMSCs exhibited higher osteogenic potential than UMSCs. Furthermore, ADMSCs and UMSCs had higher chondrogenic potential than BMMSCs. This study demonstrated that chondrogenic ADMSCs- or UMSCs-seeded hDCB might be potential osteochondral constructs for osteochondral regeneration.