Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs.
In six conscious dogs with esophageal, gastric, and pancreatic fistulas, the effects of intravenous infusion of neurotensin and intraduodenal instillation of sodium oleate on gastric and pancreatic secretion were determined under basal conditions and after exogenous (secretin and cholecystokinin octapeptides) or endogenous stimulants (feeding and duodenal acidification). Neurotensin given intravenously in graded doses (1.5-200 pmol . kg-1 . min-1) to fasted dogs produced a dose-dependent stimulation of pancreatic bicarbonate and protein secretion reaching, respectively, about 18 and 100% of maximal responses to secretin and cholecystokinin octapeptide (CCK). Duodenal oleate in graded doses (0.5-16 mmol/h) resulted in a similar pattern of bicarbonate and protein secretion but increased plasma neurotensin only to about 10% of that achieved with infusion of exogenous neurotensin producing an equal rate of pancreatic secretion. Neurotensin, like oleate, potentiated the action of secretin and CCK on pancreatic bicarbonate and had additive effects on protein response to these secretagogues. Both neurotensin and oleate increased pancreatic response to liver extract meal kept in the stomach at constant pH (5.5) and the response to sham feeding but decreased the response to ordinary feeding, probably due to the inhibition of gastric acid secretion and reduction of duodenal acidification. Neurotensin given intra-arterially directly to the pancreas or to isolated intestinal segment increased dose dependently the blood flow and oxygen consumption without affecting general circulation. We conclude that 1) neurotensin mimics the pancreatic secretory effects of intestinal fat, 2) neurotensin may contribute in part to fat-induced stimulation of the pancreatic secretion, and 3) the secretory effects of neurotensin are accompanied by a marked stimulation of intestinal and pancreatic circulation and metabolism.


Comparison of the Peabody Picture Vocabulary Test-Third Edition and Wechsler Adult Intelligence Scale-Third Edition with university students.
This study examined the relationship between the Peabody Picture Vocabulary Test-Third Edition (PPVT-III) and Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) using 40 adults who ranged in age from 18 to 41 (mean age of 22 years). Participants were administered the PPVT-III and WAIS-III in counterbalanced fashion to control for order effects. Results revealed that the PPVT-III score was related to the WAIS-III Verbal IQ (VIQ) and Full Scale IQ (FSIQ) scores but unrelated to the Performance IQ (PIQ) score. In addition, analyses indicated that, while there were no significant differences between the PPVT-III score and WAIS-III mean FSIQ and PIQ scores, the PPVT-III mean score was significantly lower than the WAIS-III VIQ. Further analysis indicated that the PPVT-III adequately estimated WAIS-III FSIQ and VIQ scores for participants who were classified as Average or High Average on the WAIS-III. However, for participants in the Superior range, the PPVT-III tended to underestimate FSIQ and VIQ scores by approximately 10 points.


The effects of angiotensin-receptor blockers on mortality and morbidity in heart failure: a systematic review.
Trials evaluating angiotensin-receptor blockers in heart failure (HF) have shown inconsistent results. To evaluate the effect of angiotensin II (AII) receptor blockers in HF patients on total mortality and HF hospitalisations. Systematic search of the literature through MEDLINE (1980-2007) and abstracts of major cardiovascular congresses from 2002 to 2007. (i) randomised controlled trials with more than 500 patients and follow up > 6 months, (ii) availability of total mortality and/or (iii) availability of hospital admission because of worsening HF. Data retrieved by two independent reviewers. DerSimonian random effects model was used. Mortality data were available from 27,495 patients. When AII receptor blockers plus angiotensin-converting enzyme inhibitors (ACE-I) were compared with ACE-I in chronic HF trials, the relative risk (RR) for death was 0.98 (95% CI: 0.84-1.15). When AII receptor blockers were compared with ACE-I the RR for death was 1.06 (95% CI: 0.56-1.62). Similar results were found for postmyocardial infarction trials. The effects on hospital admission revealed a RR of 0.83 (95% CI: 0.71-0.97) and 1.09 (95% CI: 0.74-1.60) respectively. Angiotensin II receptor blockers did not show any beneficial effect on mortality when used in combination with ACE-I or when compared with ACE-I alone. A 17% reduction in hospital admissions was observed.


[Validation of the general help-seeking questionnaire for mental health problems in adolescents].
Help-seeking behavior is a protective factor in young people, essential for their mental health, well-being and development. However, some adolescents do not seek professional help when they need to. In this context, it is relevant to study the help-seeking behavior for mental health problems in adolescent population. To adapt and validate the general help-seeking questionnaire for mental health problems in Chilean adolescents. Cross-sectional and correlational study of a non-random sample of 793 adolescent students, between 14 and 19 years old, from the city of Talca (Chile). The general help-seeking questionnaire, vignette version, (GHSQ-V) was administered after a transcultural adaptation and criterion validation. Descriptive statistics, exploratory factor analysis and non-parametric Mann-Whitney U test were used for analysis. An exploratory analysis identified two factors regarding available sources of help: 1) informal sources; 2) formal sources. Reliability was calculated separately for each of the health problems, resulting alpha values ranging from 0.87 to 0.75. In addition, the scale showed significant association with the variables self-efficacy and depression in the hypothesized directions. Finally, significant differences were identified in the willingness to seek help by adolescent's level of mental health literacy, for all mental health issues presented, except suicide. The adaptation of the GHSQ-V for Chilean adolescent and youth population is a valid and reliable instrument to measure willingness to seek help for mental health problems in our socio-cultural environment.


Development of long-circulating docetaxel loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles: Optimization, pharmacokinetic, cytotoxicity and in vivo assessments.
Long-circulating nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett-Burman (PBD) and Box-Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39±0.85%. The particle size of the nanoparticles was found to be 260±2.85nm, while the zeta potential was -18±2.12mV, indicating more stable particles. SEM, TEM, and AFM were used for characterization of surface morphology and the physicochemical characters of NPs. A pharmacokinetic evaluation carried out intravenous administration in healthy Charles Foster rats displayed enhanced systemic bioavailability and plasma drug concentration. The in vivo-in silico assessment by GastroPlus™ showed good prediction accuracy and presented best-fit model. Nanoparticles were also studied for stability testing and were found to be stable concerning their drug content and physical characters. In vitro cytotoxicity was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. Anticancer studies of optimized NPs showed a significant increase in efficacy as observed by relative tumor volume up to 30 days.


College students' preferences for health care providers when accessing sexual health resources.
Many emerging adults (18-25 year olds) report unmet health needs and disproportionately experience problems such as sexually transmitted infections. This study was conducted to examine college students' perceptions of health care providers, specifically in the context of accessing sexual health resources. Students (N = 52) were recruited from five diverse colleges in one state to participate in a one-to-one interview that involved walking and virtually exploring resources on and near campus. Interviews were conducted from May to November 2010. Open-ended one-to-one interview questions. Inductive qualitative analysis yielded six themes summarizing students' perceptions of provider characteristics, health care resources, the role of their peers, and students' suggestions for strengthening health care services. Importantly, students consider a variety of staff-and their student peers-to be resources for sexual health information and services. Findings emphasize the importance of collaboration between health service staff and broader campus staff because students often turn to campus staff initially. Postsecondary students welcome opportunities to know a provider through interactive websites that include details about providers on campus; their decisions to seek sexual health care services are influenced by their perceptions of providers' characteristics and interpersonal skills.


Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit.
The effects of forskolin, isoprenaline, sodium nitroprusside and the frequency of stimulation were examined on cyclic nucleotide levels and tension responses in rabbit isolated right ventricular papillary muscles. Increasing the frequency of stimulation from 0.01 Hz to 1.6 Hz induced positive inotropic responses that were not obviously related to alterations in the level of either cyclic AMP or cyclic GMP. Isoprenaline induced rapid, concentration-related positive inotropic responses that were associated with increases in the levels of both cyclic AMP and cyclic GMP. There existed good correlations between the increases in tension and the concentrations of both cyclic nucleotides measured in the tissues. Forskolin induced concentration-related positive inotropic responses that were slow to develop. These responses were accompanied by concentration-related increases in the levels of cyclic AMP but not cyclic GMP. The tension responses correlated well with the levels of cyclic AMP measured. The cyclic AMP levels produced by forskolin were some 8 fold higher than those induced by isoprenaline for similar increases in tension. Sodium nitroprusside was without inotropic effect either positive or negative; it nevertheless elevated cyclic GMP levels whilst slightly reducing cyclic AMP levels. These data show that the ratio of cyclic AMP to cyclic GMP does not correlate well with changes in mammalian cardiac contractility. The data further suggest that whilst the intracellular concentration of cyclic AMP in rabbit ventricular myocardium may be an important determinant of positive inotropism, the relationship between the two parameters is more complex than simple proportionality between the tension generated and the amount of cyclic AMP measured within the cells.


Influence of multiple scattering on the resolution of an imaging system: a Cramér-Rao analysis.
We revisit the notion of resolution of an imaging system in the light of a probabilistic concept, the Cramér-Rao bound (CRB). We show that the CRB provides a simple quantitative estimation of the accuracy one can expect in measuring an unknown parameter from a scattering experiment. We then investigate the influence of multiple scattering on the CRB for the estimation of the interdistance between two objects in a typical two-sphere scattering experiments. We show that, contrarily to a common belief, the occurence of strong multiple scattering does not automatically lead to a resolution enhancement.


Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex.
Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.


Discovery of antitumor indolocarbazoles: rebeccamycin, NSC 655649, and fluoroindolocarbazoles.
A fermentation directed product search for potential anticancer drugs conducted by Bristol-Myers in the 1970s and early 1980s resulted in the identification of a novel indolocarbazole (IC) rebeccamycin (RBM) as a potential drug development candidate. Subsequently, an analog program designed to impart distal site in vivo antitumor activity resulted in the discovery of diethylaminoethyl analog of RBM (DEAE-RBM), which is presently undergoing clinical evaluation as NSC 655649 and BMY-27557. Strong DNA intercalation is the primary mechanism of action of DEAE-RBM resulting in the potent catalytic inhibition of both topoisomerases I and II. Precursor feeding fermentation experiments with fluorine-substituted tryptophans yielded novel fluoroindolocarbazoles (FICs). These FICs were identified as targeting topoisomerase (topo) I in a mechanism-based screen and their action on topo I was confirmed by production of topo I-mediated single-strand breaks in DNA at sites essentially identical to those induced by camptothecin. Topo I dependent cytotoxicity was demonstrated for specific FICs using a P388 and camptothecin-resistant P388/CPT45 pair of cell lines, the latter expresses little or no functional topo I. For example, topo I selectivity was greatest with 3,9-difluoro substituted FIC and was least significant and least cytotoxic with 4,8-difluoro substituted FIC. The review focuses on the discovery of the rebeccamycin class of compounds and their structure-activity relationships leading to the development of the clinical candidate BMY-27557 (NSC 655649), as well as the lead identification of the fluoroindolocarbazole class of compounds.


Relationship between breast arterial calcifications detected on mammography and brachial artery intima-media thickness.
Although breast arterial calcification (BAC) was shown to be related with coronary artery disease (CAD), hypertension (HT), diabetes mellitus (DM) and carotid intima-media thickness (C-IMT), but the association between BAC and brachial intima-media thickness (B-IMT) has not been evaluated yet. Our aim was to investigate whether associations existed between BAC and measure B-IMT and atherosclerosis (AS) by comparing these patients with healthy control subjects. A Total of 75 patients were included in the study. Subjects with or without BAC were assigned into one of two groups and those with a BAC were graded. Main brachial artery IMT was measured. When the effect of age was partialled out statistically, we found a statistically significant difference in mean B-IMT between BAC (+) (0.54 ± 0.09) and BAC (-) (0.45 ± 0.08) groups (p = 0.001) after the groups were adjusted for age. In conclusion, even though the relationship between B-IMT and BAC was significant, like the relationship between C-IMT and BAC, significant age difference between BAC (+) and BAC (-) groups and no significant relationship between BAC and time after menopause, after adjustment for age, suggest a strong association between BAC and age rather than AS. This can be elucidated by pathological correlation studies in larger series of subjects.


Population-based study of lung function and incidence of heart failure hospitalisations.
Reduced forced expiratory volume (FEV(1)) and forced vital capacity (FVC) are risk factors for myocardial infarction (MI) and stroke. However, the relationship with incidence of heart failure (HF) is incompletely known. This population-based study explored whether reduced FEV(1) or FVC is associated with the incidence of hospitalisation for HF. 20 998 men (mean age 43 years) with no history of MI or stroke were examined with spirometry in 1974-84. The incidence of hospitalisation due to HF was studied over a mean follow-up of 23 years in relation to age- and height-adjusted FEV(1) and FVC. 725 incident HF hospitalisations occurred during the follow-up period, 503 of them without a previous or concurrent diagnosis of MI. In non-smokers the risk factor-adjusted hazard ratio (HR) for HF hospitalisation was 1.25 (95% CI 1.11 to 1.40) and 1.26 (95% CI 1.13 to 1.42), respectively, per 1SD lower FEV(1) and FVC. The corresponding risk factor-adjusted HRs in smokers were 1.32 (95% CI 1.21 to 1.45) and 1.22 (95% CI 1.11 to 1.33), respectively, for FEV(1) and FVC. This relationship was consistent in men with and without hypertension, in men above and below the median age of 44 years and for HF events without previous or concurrent MI. Exclusion of cases with a diagnosis of chronic obstructive pulmonary disease during the follow-up period did not substantially change the results. In this long-term population-based study of men, moderately reduced FEV(1) and FVC were associated with an increased incidence of hospitalisations due to HF.


Performance of Cytokine Storm Syndrome Scoring Systems in Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children.
The objective of this study is to evaluate pediatric patients using existing macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH) scoring systems to determine how these systems identify patients with cytokine storm syndrome (CSS) in the setting of a multisystem inflammatory syndrome in children (MIS-C) and active coronavirus disease 2019 (COVID-19) infection. Hospitalized pediatric patients with MIS-C and active COVID-19 infection at a single institution were identified. Infectious data, clinical findings, and laboratory values were collected, and patients were stratified by disease severity. Eight historically used scoring systems for MAS, HLH, and CSS were examined in the cohort of patients with MIS-C and pediatric COVID-19. The HLH-2004 criteria and HScore did not identify any patients as having CSS on admission, with only one patient with COVID-19 meeting criteria at peak disease severity. The 2016 systemic juvenile idiopathic arthritis (sJIA)/MAS criteria, ferritin/erythrocyte sedimentation rate (ESR) ratio, and COVID-19 CSS Quick Score most frequently identified CSS in this population and distinguished between COVID-19 and MIS-C hyperinflammation. The 2019 MAS/sJIA (MS) score and the COVID-19-associated hyperinflammatory syndrome (cHIS) criteria were less likely to identify CSS, as the MS score overestimated CSS and the cHIS resulted in similar scores regardless of severity or disease type. The Caricchio COVID-Cytokine Storm (COVID-CS) criteria identified patients with COVID-19 frequently but was less useful in MIS-C because of its COVID-19-specific criteria. MIS-C and pediatric COVID-19 result in relatively unique CSSs and patterns of inflammation. Existing scoring systems for CSSs likely do not capture the full breadth of this disease process in MIS-C and pediatric COVID-19.


U.S. Political Parties and Support for Suicide Prevention.
As a public health problem, suicidal behavior demands a community-level response, including government action. We aimed to test whether support for suicide prevention in the United States has been independent from political party affiliation (Democrat and Republican). Actions from both political parties have supported suicide prevention efforts. The only differences in support based on party affiliation showed greater support from the Democrat Party in one instance, and the Republican Party in the other. The results were consistent with the hypothesis that degree of support for suicide prevention cannot be predicted solely by political party.


Incidence, course, and prediction of hyperbilirubinemia in near-term and term newborns.
In this study, we investigated prospectively the incidence of significant hyperbilirubinemia and demographic and laboratory characteristics and pattern of serum bilirubin levels of near-term newborns (35-37 weeks' [245-265 days'] gestation) by comparing them with those of term newborns (38-42 weeks' [266-294 days'] gestation) longitudinally in the first 7 days of life; we also aimed to determine the value of an early (6th-hour) serum bilirubin measurement in predicting the development of significant hyperbilirubinemia later during the first week of life in near-term newborns. Serum total bilirubin measurements were initially made at the 6th hour of life and repeated daily for the next 4 days, and a last measurement was performed on the 7th day (150th hour) in 219 term newborns (term group) and 146 near-term newborns (near-term group). Newborns with serum total bilirubin levels of > or =8 and > or =12 mg/dL on day 2, > or =12 and > or 15 mg/dL on day 3, and > or =14 and > or =17 mg/dL on days 4, 5, and 7 for birth weights 2000 to 2500 g and >2500 g, respectively, were defined to have significant hyperbilirubinemia, and phototherapy treatment was started. The predictive ability of the 6th-hour serum total bilirubin value in determining the development of significant hyperbilirubinemia in the near-term group was assessed on the basis of the placement of any of the first week's serum bilirubin measurements in the > or =95th percentile of the study population. A Gaussian distribution curve, the 5th, 30th, 60th, and 95th percentiles, and 4 percentile tracks were obtained from mean serum total bilirubin values. On the basis of the percentile tracks with various sensitivity, specificity, and negative and positive predictive values, a nomogram demonstrating the 4 percentile tracks as risk-zone demarcators with divided risk zones was produced. Twenty-three newborns (10.5%) in the term group and 37 newborns (25.3%) in the near-term group had significant hyperbilirubinemia and required phototherapy. When the daily mean serum bilirubin levels of the 2 groups were compared, the first 4 days' values did not significantly differ between the 2 groups, whereas the 5th and 7th days' values were significantly higher in the near-term group. There were significant differences between the 2 groups with respect to the incidence of significant hyperbilirubinemia, hematocrit, Apgar score, and mode of delivery. On the age-specific nomogram, the zone >95th percentile was labeled as high risk, and that <5th percentile was labeled as low risk. Serum total bilirubin values between the 5th and 30th, 30th and 60th, and 60th and 95th percentiles were designated as being in the low-intermediate, intermediate, and high-intermediate risk zones, respectively. The 5th and 95th percentiles on the nomogram had the highest sensitivity (100%) and specificity (98.2%), respectively, in predicting the subsequent development of significant hyperbilirubinemia. Near-term newborns should not be treated as term newborns in the approach to management of hyperbilirubinemia, because infants of 35 to 37 weeks' gestation had significantly lower birth weights, significantly higher serum total bilirubin levels on days 5 and 7, and were 2.4 times more likely to develop significant hyperbilirubinemia than those of 38 to 42 weeks' gestation in the present study. In near-term newborns of 35 to 37 weeks' (245 to 265 days') gestation, the decision to diagnose and treat significant hyperbilirubinemia should be made on the basis of risk status (percentile distribution of the serum bilirubin values on postnatal age) rather than using birth-weight-based thresholds. A nomogram constructed from daily serum bilirubin values of each population, as we present herein, can be used in assessing the age (hour)-specific jaundice risk (high, intermediate, or low) of each near-term newborn.


Effect of the interparticle potential on the yield stress of amorphous solids.
A crucially important material parameter for all amorphous solids is the yield stress, which is the value of the stress for which the material yields to plastic flow when it is strained quasistatically at zero temperature. It is difficult in laboratory experiments to determine what parameters of the interparticle potential affect the value of the yield stress. Here we use the versatility of numerical simulations to study the dependence of the yield stress on the parameters of the interparticle potential. We find a very simple dependence on the fundamental scales that characterize the repulsive and attractive parts of the potential, respectively, and offer a scaling theory that collapses the data for widely different potentials and in different space dimensions.


Spina bifida and anencephaly: miscarriage as possible cause.
In two retrospective Liverpool surveys the domestic, family, dietary, and medical environments of the mothers of children affected by anencephaly or spina bifida, or both (ASB) were examined. None seemed to be of more than minor importance and the findings of others were therefore examined to see if they suggested a major factor. The most promising lead came from the hypothesis that ASB is usually due to an interaction between twin fetuses or between a fetus and residual trophoblastic material from the previous normal pregnancy, particularly when this is of the opposite sex to the propositus. The sex finding was not confirmed. It was noted that hydatidiform moles, like children with ASB, were usually female and that moles and choriocarcinomas on the one hand and children with ASB on the other occurred in mothers of similar ages, but were to some extent reciprocal in geographical incidence. This suggested that trophoblastic disease might be a factor common to all three and if so then one would expect the frequency of miscarriages to be higher immediately before than immediately after the birth of an ASB child, since mole and choriocarcinoma seldom follow a normal pregnancy. An analysis of published data confirmed that this was almost certainly so. Hence residual pathological trophoblastic material from either a previous miscarriage or a co-twin may interact unfavourably with another fetus to produce ASB and this may be the primary cause of the condition. The hypothesis is consistent with the observed lack of concordance in twins, the high incidence in females, the maternal age effect, and the greater prevalence in social classes IV and V.


Scleral Flap Wound Dehiscence with Valsalva Maneuver After Trabeculectomy with Mitomycin C.
Incisional surgeries such as trabeculectomy reduce the resistance of the eye to trauma. Trabeculectomy is often performed together with mitomycin C, and late onset hypotony is already an expected complication in these eyes. This case report presents a patient who developed dehiscence of the scleral flap and hypotony maculopathy after Valsalva maneuver after 5.5 years of trabeculectomy. In a 6-month period, the patient's hypotonic maculopathy became evident, and vision was affected after this period. Thereupon, the wound site was explored, and dehiscence of the scleral flap at the temporal wound site and increased aqueous outflow were detected. Repair was done with sterile pericardium patch. Post-operative vision, intraocular pressure, and hypotony maculopathy recovered very quickly. After incisional surgeries, patients should be warned against both external trauma and minor traumas such as eye rubbing and Valsalva maneuver.


Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction: A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial.
In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Percutaneous coronary intervention in addition to optimal medical therapy. Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. ClinicalTrials.gov Identifier: NCT01920048.


Attribute-Aware RBFs: Interactive Visualization of Time Series Particle Volumes Using RT Core Range Queries.
Smoothed-particle hydrodynamics (SPH) is a mesh-free method used to simulate volumetric media in fluids, astrophysics, and solid mechanics. Visualizing these simulations is problematic because these datasets often contain millions, if not billions of particles carrying physical attributes and moving over time. Radial basis functions (RBFs) are used to model particles, and overlapping particles are interpolated to reconstruct a high-quality volumetric field; however, this interpolation process is expensive and makes interactive visualization difficult. Existing RBF interpolation schemes do not account for color-mapped attributes and are instead constrained to visualizing just the density field. To address these challenges, we exploit ray tracing cores in modern GPU architectures to accelerate scalar field reconstruction. We use a novel RBF interpolation scheme to integrate per-particle colors and densities, and leverage GPU-parallel tree construction and refitting to quickly update the tree as the simulation animates over time or when the user manipulates particle radii. We also propose a Hilbert reordering scheme to cluster particles together at the leaves of the tree to reduce tree memory consumption. Finally, we reduce the noise of volumetric shadows by adopting a spatially temporal blue noise sampling scheme. Our method can provide a more detailed and interactive view of these large, volumetric, time-series particle datasets than traditional methods, leading to new insights into these physics simulations.


Multifactorial analysis of the stochastic epigenetic variability in cord blood confirmed an impact of common behavioral and environmental factors but not of in vitro conception.
An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted. This study aims to evaluate the effect of ART and other common behavioral or environmental factors associated with pregnancy on stochastic epigenetic variability using a multivariate approach. DNA methylation levels of cord blood from 23 in vitro and 41 naturally conceived children were analyzed using the Infinium HumanMethylation450 BeadChips. After multiple testing correction, no statistically significant difference emerged in the number of cord blood stochastic epigenetic variations or in the methylation levels between in vitro- and in vivo-conceived babies. Conversely, four multiple factor analysis dimensions summarizing common phenotypic, behavioral, or environmental factors (cord blood cell composition, pre or post conception supplementation of folates, birth percentiles, gestational age, cesarean section, pre-gestational mother's weight, parents' BMI and obesity status, presence of adverse pregnancy outcomes, mother's smoking status, and season of birth) were significantly associated with stochastic epigenetic variability. The stochastic epigenetic variation analysis allowed the identification of a rare imprinting defect in the locus GNAS in one of the babies belonging to the control population, which would not have emerged using a classical case-control association analysis. We confirmed the effect of several common behavioral or environmental factors on the epigenome of newborns and described for the first time an epigenetic effect related to season of birth. Children born after ART did not appear to have an increased risk of genome-wide changes in DNA methylation either at specific loci or randomly scattered throughout the genome. The inability to identify differences between cases and controls suggests that the number of stochastic epigenetic variations potentially induced by ART was not greater than that naturally produced in response to maternal behavior or other common environmental factors.


Decortication for childhood empyema. The primary provider's peccadillo.
Of the 31 children treated for empyema thoracis secondary to pneumonitis at the Loma Linda University Medical Center, Loma Linda, Calif, from 1980 to 1990, 23 responded to prompt directed antibiotic therapy coupled with drainage, usually tube thoracostomy. All patients were cured clinically; some demonstrated residual pleural reaction with chest roentgenography or computed tomography that resolved over time. Decortication was necessary in eight severely ill children; three required concurrent lung resection for abscess. Distinct from the nonoperated group, there was a pattern of initial antibiotic trials in these patients averaging 6.5 different drugs plus delayed drainage of effusions. Delay in the initiation of antibiotic therapy was six times longer for the operated vs the nonoperated group. Delay to tube thoracostomy was 18 days for the decorticated children compared with 5.4 days for the nondecorticated children. All eight children responded completely and rapidly to their decortications. Roentgenographic changes lagged considerably behind the clinical course of the child, and computed tomographic scans provided better identification of chest tube placement but little information predictive of the need for decortication. Decortication for empyema seldom is necessary when a child is treated promptly with appropriate antibiotics directed by thoracentesis findings, and drainage, usually tube thoracostomy. The criterion for decortication is persistent sepsis, not the roentgenographic appearance of the chest.


Fetal Urinary Tract Anomalies: Review of Pathophysiology, Imaging, and Management.
Common fetal anomalies of the kidneys and urinary tract encompass a complex spectrum of abnormalities that can be detected prenatally by ultrasound. Common fetal anomalies of the kidneys and urinary tract can affect amniotic fluid volume production with the development of oligohydramnios or anhydramnios, resulting in fetal pulmonary hypoplasia and, potentially, abnormal development of other fetal structures. We provide an overview of common fetal anomalies of the kidneys and urinary tract with an emphasis on sonographic patterns as well as pathologic and postnatal correlation, along with brief recommendations for postnatal management. Of note, we render an updated classification of fetal abnormalities of the kidneys and urinary tract based on the presence or absence of associated urinary tract dilation. In addition, we review the 2014 classification of urinary tract dilation based on the Linthicum multidisciplinary consensus panel.


Interleukin-13 (IL-13)-A Pleiotropic Cytokine Involved in Wound Healing and Fibrosis.
The liver, as a central metabolic organ, is systemically linked to metabolic-inflammatory diseases. In the pathogenesis of the metabolic syndrome, inflammatory and metabolic interactions between the intestine, liver, and adipose tissue lead to the progression of hepatic steatosis to metabolic-dysfunction-associated steatohepatitis (MASH) and consecutive MASH-induced fibrosis. Clinical and animal studies revealed that IL-13 might be protective in the development of MASH through both the preservation of metabolic functions and Th2-polarized inflammation in the liver and the adipose tissue. In contrast, IL-13-associated loss of mucosal gut barrier function and IL-13-associated enhanced hepatic fibrosis may contribute to the progression of MASH. However, there are only a few publications on the effect of IL-13 on metabolic diseases and possible therapies to influence them. In this review article, different aspects of IL-13-associated effects on the liver and metabolic liver diseases, which are partly contradictory, are summarized and discussed on the basis of the recent literature.


Cyclic fatigue and energy-dispersive X-ray spectroscopy examination of the novel ROTATE instrument.
To investigate the cyclic fatigue resistance of novel ROTATE instruments and to compare with the same size of One Curve, TF adaptive, and Mtwo instruments using a root canal simulation model. Four-type of 25/0.06 instruments were used: ROTATE, Mtwo, One Curve, TF adaptive. Instruments were divided into two subgroups: Distilled water and 2.5% sodium hypochlorite (n = 20). Instruments were operated at 35°C. The time to fracture and the length of the fractured fragments were compared One-way analysis of variance (ANOVA) followed by Tukey's multiple comparison tests (p < .05). Descriptive analysis was performed for the elemental composition of instruments by Energy-dispersive X-ray spectroscopy. ROTATE demonstrated the lowest Ni content and SD values. ROTATE had significantly higher NCF values than other groups (p < .0001). Sodium hypochlorite was decreased the mean NCF values. This is the first study in the literature on the cyclic fatigue of ROTATE. ROTATE presented higher cyclic fatigue life than One Curve, TF Adaptive, and Mtwo.


Ultrahigh scan-rate quasi-distributed acoustic sensing system using array match interrogation.
Inspired by compressed sensing techniques, a method for significantly enhancing the maximum allowable scan rate in quasi-distributed acoustic sensing (Q-DAS) is described and studied. Matching the scan parameters to the interrogated array facilitates orders of magnitude improvement in the scan rate and a corresponding increase in the maximum slew rate (SR) of differential phase variations which can be measured without ambiguity. The method is termed array matched interrogation (AMI). To improve the method's SNR, maximum number of sensing sections and maximum range, the interrogation pulse can be replaced by a perfect periodic autocorrelation (PPA) code. This version of the method is referred to as coded array matched interrogation (C-AMI). The implementation of C-AMI is not trivial and requires special design rules which are derived and tested experimentally. The design rules ensure that the 'folding' of the returning peaks of the Q-DAS array into a scan period, which is much shorter than the fiber's roundtrip time, will not lead to overlaps. The method demonstrated a scan rate of 20 times higher than the common limit and measurement of unprecedented slew-rate of 10.5 ×106 rad/s.


Structural and immunological characterization of the intracellular forms of an abundant 68,000 Mr human cytomegalovirus protein.
Murine monoclonal antibodies and polyvalent monospecific antisera reactive with an abundant 68,000 Mr (p68) human cytomegalovirus (CMV) virion protein were used to characterize this protein within CMV-infected cells. The protein was found to partition within the nucleus and cytoplasm of infected cells. Pulse-chase analysis indicated the p68 was degraded into three proteins of 52,000, 51,000 and 50,000 Mr which were found only within infected cells. Both cellular forms as well as the virion p68 were phosphorylated but non-glycosylated. The p68 was synthesized shortly after infection and in the presence of cytosine arabinoside, an inhibitor of viral DNA replication. Studies with monospecific antisera and a panel of monoclonal antibodies specific for the p68 suggested that this protein was not expressed on the surface of infectious virions or infected cells.


A partial intensity invariant feature descriptor for multimodal retinal image registration.
Detection of vascular bifurcations is a challenging task in multimodal retinal image registration. Existing algorithms based on bifurcations usually fail in correctly aligning poor quality retinal image pairs. To solve this problem, we propose a novel highly distinctive local feature descriptor named partial intensity invariant feature descriptor (PIIFD) and describe a robust automatic retinal image registration framework named Harris-PIIFD. PIIFD is invariant to image rotation, partially invariant to image intensity, affine transformation, and viewpoint/perspective change. Our Harris-PIIFD framework consists of four steps. First, corner points are used as control point candidates instead of bifurcations since corner points are sufficient and uniformly distributed across the image domain. Second, PIIFDs are extracted for all corner points, and a bilateral matching technique is applied to identify corresponding PIIFDs matches between image pairs. Third, incorrect matches are removed and inaccurate matches are refined. Finally, an adaptive transformation is used to register the image pairs. PIIFD is so distinctive that it can be correctly identified even in nonvascular areas. When tested on 168 pairs of multimodal retinal images, the Harris-PIIFD far outperforms existing algorithms in terms of robustness, accuracy, and computational efficiency.


Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactoferrin in animals.
Bovine lactoferrin (bLF), a milk protein known to have bacteriostatic properties was examined for its preventive effects on colon and other organ carcinogenesis and experimental metastasis. (Experiment 1) The influence on colon carcinogenesis was investigated in male rats treated with azoxymethane (AOM), then received 2 or 0.2% bLF for 36 weeks. Significant reduction in the incidence (27% and 46% of the control, respectively) and number of adenocarcinomas of the large intestine was observed. (Experiment 2) In BALB/c mice bearing subcutaneous (s.c.) implants of colon carcinoma 26 (Co 26Lu). bLF demonstrated significant inhibition of spontaneous lung metastasis (approximately 43% of the control). Number of cytotoxic asialoGM1+ and CD8+ cells in white blood cells increased (171% and 122% of control, respectively) after treatment. Results of those experiments indicate that bLF remarkably prevents colon carcinogenesis and lung metastasis of colon carcinoma cells, possibly due to increasing cytotoxic cells in the peripheral blood.


Evidence for genetic hitchhiking effect associated with insecticide resistance in Aedes aegypti.
Information on genetic variation within and between populations is critical for understanding the evolutionary history of mosquito populations and disease epidemiology. Previous studies with Drosophila suggest that genetic variation of selectively neutral loci in a large fraction of genome may be constrained by fixation of advantageous mutations associated with hitchhiking effect. This study examined restriction fragment length polymorphisms of four natural Aedes aegypti mosquito populations from Trinidad and Tobago, at 16 loci. These populations have been subjected to organophosphate (OP) insecticide treatments for more than two decades, while dichlor-diphenyltrichlor (DDT) was the insecticide of choice prior to this period. We predicted that genes closely linked to the OP target loci would exhibit reduced genetic variation as a result of the hitchhiking effect associated with intensive OP insecticide selection. We also predicted that genetic variability of the genes conferring resistance to DDT and loci near the target site would be similar to other unlinked loci. As predicted, reduced genetic variation was found for loci in the general chromosomal region of a putative OP target site, and these loci generally exhibited larger F(ST) values than other random loci. In contrast, the gene conferring resistance to DDT and its linked loci show polymorphisms and genetic differentiation similar to other random loci. The reduced genetic variability and apparent gene deletion in some regions of chromosome 1 likely reflect the hitchhiking effect associated with OP insecticide selection.


Orbscan mapping in Ehlers-Danlos syndrome.
A candidate for refractive surgery presented with classic (type I) Ehlers-Danlos syndrome (EDS). Clinical examination revealed blue sclera, limbus-to-limbus corneal thinning, myopia, and astigmatism. Orbscan (Bausch & Lomb) pachymetry mapping provided a striking demonstration of the limbus-to-limbus thinning with a central corneal thickness of 360 microm in the right eye and 383 microm in the left eye and midperipheral corneal thickness ranging from 370 to 438 microm and 376 to 434 microm, respectively. Despite the theoretical biomechanical weakness from the thin cornea and defective collagen, regular surface topography was maintained without the development of keratoconus. Although all types of EDS remain a contraindication to laser refractive surgery, Orbscan mapping provides a valuable insight into corneal shape and thickness in this condition.


Evaluation of Baseline Characteristics and Prognostic Factors in Multisystemic Inflammatory Syndrome in Children: Is It Possible to Foresee the Prognosis in the First Step?
Background: Two years after the first cases, critical gaps remain in identifying prognostic factors in multisystem inflammatory syndrome in children (MIS-C). Methods: This retrospective study included 99 patients with MIS-C hospitalized between August 2020 and March 2022 in a pediatric tertiary center. The patients were divided into two groups according to clinical severity (low- and high-risk). Prognostic values of baseline clinical and laboratory characteristics were evaluated with advanced statistical analysis, including machine learning. Results: Sixty-three patients were male, and the median age was 83 (3−205) months. Fifty-nine patients (59.6%) were low-risk cases. Patients aged six years and over tended to be at higher risk. Involvement of aortic or tricuspid valve or >1 valve was more frequent in the high-risk group. Mortality in previously healthy children was 3.2%. Intensive care unit admission and mortality rate in the high-risk group were 37.5% and 7.5%, respectively. At admission, high-risk patients were more likely to have reduced lymphocyte count and total protein level and increased brain natriuretic peptide (BNP), ferritin, D-dimer, and troponin concentrations. The multiple logistic regression model showed that BNP, total protein, and troponin were associated with higher risk. When the laboratory parameters were used together, BNP, total protein, ferritin, and D-dimer provided the highest contribution to the discrimination of the risk groups (100%, 89.6%, 85.6%, and 55.8%, respectively). Conclusions: Our study widely evaluates and points to some clinical and laboratory parameters that, at admission, may indicate a more severe course. Modeling studies with larger sample groups are strongly needed.


Scientific community. Soft money's hard realities.
"Second-class citizen" is how researchers on soft money, who have to raise their salaries from grants, describe their position--even those who like their jobs. It can be fraught with financial insecurity, disrespect, and poor facilities--as well as some advantages, such as freedom from administrative duties. Those who have done it say that success requires a strong will, an accommodating department, friends in high places, and money in the bank as a cushion--not to mention emotional security and a tough skin.


Epidemiology of breastfeeding in Italy.
To evaluate the rates of initiation and duration of breastfeeding in the major geographical areas of Italy, 1601 mothers randomly selected as representative of the November 1995 deliveries in all 20 regional districts underwent interviews within 1 mo after delivery. A cross-sectional telephone scanner-ready questionnaire was administered by trained personnel. Mothers who started breastfeeding were interviewed again at 3, 6, 9 and 12 mo after delivery. The results indicate that 85.3% mothers initiated breastfeeding, with significant geographical differences (rate ranging from 75.8% in the islands to 90.8% in the north-east; p < 0.0001). The overall breastfeeding prevalence considering all 1601 mothers decreased steadily to 41.8% at 3 mo and 19.4% at 6 mo, and was even lower when considering only exclusive/predominant breastfeeding (37.3% and 8.1%, respectively). The duration of breastfeeding was shorter in the islands than in other areas, particularly the north-east (p = 0.001). Although the rate of breastfeeding initiation is fairly high in Italy, the rapid decrease in breastfeeding practice throughout the first 6 mo requires strategies for improvement. The differences between the continental areas and the islands should be considered in programming intervention plans.


Composition and structural effects on the adsorption of ionic liquids onto activated carbon.
The applications and variety of ionic liquids (ILs) have increased during the last few years, and their use at a large scale will require their removal/recovery from wastewater streams. Adsorption on activated carbons (ACs) has been recently proposed for this aim and this work presents a systematic analysis of the influence of the IL chemical structures (cation side chain, head group, anion type and the presence of functional groups) on their adsorption onto commercial AC from water solution. Here, the adsorption of 21 new ILs, which include imidazolium-, pyridinium-, pyrrolidinium-, piperidinium-, phosphonium- and ammonium-based cations and different hydrophobic and hydrophilic anions, has been experimentally measured. This contribution allows an expansion of the range of IL compounds studied in previous works, and permits a better understanding of the influence of the IL structures through the adsorption on AC. In addition, the COSMO-RS method was used to analyze the measured adsorption isotherms, allowing the understanding of the role of the cationic and anionic structures in the adsorption process, in terms of the different interactions between the IL compound and AC surface/water solvent. The results of this work provide new insights for the development of adsorption as an effective operation to remove/recover ILs with very different chemical nature from water solution.


Activity of Cinnamomum osmophloeum leaf essential oil against Anopheles gambiae s.s.
The increasing status of insecticide resistant mosquitoes in sub-Saharan Africa is a threatening alert to the existing control efforts. All sibling species of An. gambiae complex have evolved insecticide resistance in wild populations for different approved classes of the insecticides currently in use in the field. An alternative compound for vector control is absolutely urgently needed. In this study, the larvicidal activity and chemical composition of the Cinnamomum osmophloeum leaf essential oils were investigated. C. osmophloeum leaf essential oils were extracted by hydrodistillation in a Clevenger-type apparatus for 6 hours, and their chemical compositions identified using GC-MS. These oils were evaluated against An. gambiae s.s. in both laboratory and semi-field situations. The WHO test procedures for monitoring larvicidal efficacy in malaria vectors were used. The composition of C. osmophloeum leaf essential oil has been found to have 11 active compounds. The most abundant compound was trans-cinnamaldehyde (70.20%) and the least abundant was caryophyllene oxide (0.08%). The larvicidal activity was found to be dosage and time dependant both in laboratory and semi-field environments with mortality ranging from 0% to 100%. The LC50 value was found to vary from 22.18 to 58.15 μg/ml in the laboratory while in semi-field environments it was 11.91 to 63.63 μg/ml. The LC90 value was found to range between 57.71 to 91.54 μg/ml in the laboratory while in semi-field environments was 52.07 to 173.77 μg/ml. Mortality ranged from 13% to 100% in the laboratory while in semi-field environments it ranged between 43% to 100% within mortality recording time intervals of 12, 24, 48, and 72 hours. The larvicidal activity shown by C. osmophloeum leaf essential oil is a promising alternative to existing larvicides or to be incorporated in integrated larval source management compounds for An. gambiae s.s control. The efficacy observed in this study is attributed to both major and minor compounds of the essential oils.


McCarey-Kaufman (MK) organ culture and MK medium-shifted corneas.
Paired human donor corneas were studied to determine the effects of temperature, osmolarity, and media shifts on the endothelium of corneas stored in McCarey-Kaufman (MK) medium initially and then shifted to standard organ culture medium. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated intact corneal endothelium in six of seven human control corneas stored in MK medium prior to fixation. Intact corneal endothelium was similarly demonstrated by specular microscopy, SEM, and TEM in seven of seven "MK-shifted" corneas. These data suggest that MK-stored donor corneas may be transferred into an organ culture system at 34 degrees C for prolonged storage with maintenance of corneal endothelial cell viability.


Vitamin D and hyperemesis gravidarum: A mendelian randomization study.
The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method. Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum. We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403-0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population. The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.


Comparison of Qualitative and Volumetric Assessments of Breast Density and Analyses of Breast Compression Parameters and Breast Volume of Women in Bahcesehir Mammography Screening Project.
We aimed to compare visual and quantitative measurements of breast density and to reveal the density profile with compression characteristics. Screening mammograms of 1399 women between May 2014 and May 2015 were evaluated by using Volpara 4th and 5th version. First 379 mammograms were assessed according to ACR BI-RADS 4th edition and compared to Volpara. We categorized the breast density in two subgroups as dens or non-dens. Two radiologists reviewed the images in consensus. Agreement level between visual and volumetric methods and volumetric methods between themselves assessed using weighted kappa statistics. Volpara data such as fibroglandular volume (FGV), breast volume (BV), compression thickness (CT), compression force (CF), compression pressure (CP) were also analyzed with relation to the age. 1399 mammograms were distributed as follows: 12.7% VDG1, 39.3% VDG2, 34.1% VDG3, 13.9% VDG4 according to the 4th edition of Volpara; 1.2% VDG1, 46% VDG2, 36.8% VDG3, 15.9% VDG4 according to the 5th edition of Volpara. The difference between two editions was 4.7% increase in dense category. 379 mammograms, according to ACR BI-RADS 4th edition, were distributed as follows: 25.9% category A, 50.9% category B, 19.8% category C, 3.4% category D. The strength of agreement between the Volpara 4th and 5th editions was found substantial (k=0.726). The agreements between visual assessment and both Volpara editions were poor (k=-0.413, k=-0.399 respectively). There was a 142% increase in dense group with the VDG 4th edition and 162% with the VDG 5th edition when compared to visual assessment. Compression force decreased while compression pressure increased with increasing Volpara Density Grade (VDG) (p for trend <0.001 for both). Compression thickness and breast volume decreased with increasing VDG (p for trend <0.001 for both). The FGV decreases with age and the breast volume increases with increasing age (p<0.001). Visual assessment of breast density doesn't correlate well with volumetric assessments. Obtaining additional information about physical parameters and breast profile by the results of quantified methods is important for breast cancer risk assessments and prevention strategies.


Serum cytokine profile in schizophrenic patients.
Schizophrenia is a chronic severe mental disorder in which immunologic imbalances have been reported. Some researchers have demonstrated dysregulation of cytokine levels in this mental disorder. Considering the possible role of cytokines in the pathogenesis or clinical course of schizophrenia, we assessed serum levels of IL-4, IL-10, IL-17A and IFN-γ in a homogenous sample of Iranian patients who were in remission under treatment with Clozapine compared with sex and age matched controls. There was a statistically significant difference in IL-4 levels between patients and healthy subjects (P= 0.023). IL-4 levels were 83% higher in cases than in control group. No significant group*gender interaction was detected suggesting the similar IL-4 levels between males and females in each study group. There was no statistically significant difference in IFN-γ levels between patients and healthy subjects, but IFN-γ levels were 70% higher in male compared with female group. No significant differences have been found in serum levels of other cytokines between cases and controls or between males and females. The higher levels of IL-4 in patients treated with Clozapine might be due to effects of this antipsychotic drug on immune responses. Future studies are needed to elaborate the exact underlying mechanism.


Prevalence of invasive ability and other virulence-associated characteristics in Providencia alcalifaciens strains isolated in São Paulo, Brazil.
Providencia alcalifaciens is an invasive enteric pathogen. The present study determined the prevalence of invasive ability in P. alcalifaciens strains isolated in São Paulo, Brazil, mainly from patients with diarrhoea. Invasion of HeLa cells was found in 17 (42%) of 41 strains studied. Most (88%) of the invasive strains were isolated from diarrhoeal stools. The invasive property was identified in 50% of P. alcalifaciens strains isolated as pure cultures or from stool samples where no other enteropathogen was identified. All the invasive strains caused actin condensation in infected cells. Plasmid profile analysis showed the presence of plasmids of 35.8-180 kb in 70% of the strains regardless of their invasive ability, suggesting that invasiveness in P. alcalifaciens is not plasmid related. No homology with a probe for gene sequences for invasion of enteroinvasive Escherichia coli and Shigella strains was identified in colony hybridisation assays. The invasive property of P. alcalifaciens was confirmed in the present study, but this characteristic did not predominate among strains isolated from patients with diarrhoea in São Paulo City. The presence of other virulence mechanisms and the role of non-invasive P. alcalifaciens strains as a cause of diarrhoea remain to be established.


Characterization of an immunosuppressive anti-CD40 ligand monoclonal antibody.
The interaction between CD40 ligand (CD40L) and its counter-receptor CD40 is critically important in T- and B-cell costimulation and generation of the humoral immune response. But several questions still remain unsolved, particularly in the human in vivo system. To clarify the precise function of CD40L and develop an immunosuppressive agent, we have generated a murine monoclonal antibody (MAb), 2B2 specific for human CD40L. The specificity of this MAb for human CD40L was verified by enzyme-linked immunoadsorbent assay (ELISA) and flow cytometry. MAb 2B2 immunoprecipitated proteins of molecular weight 35 and 28 kD on human peripheral blood lymphocytes (PBLs) stimulated with phorbol 12-myristate-13-acetate (PMA) plus ionomycin. Then we have studied the biological effect of MAb 2B2 in severe combined immunodeficiency (SCID) mice reconstituted with human PBLs. The data showed that this MAb strongly suppressed human IgG production of human B cells transplanted in SCID mice, indicating that this MAb 2B2 could be used to regulate unwanted immune responses associated with autoimmune disease. Then we analyzed the sequence of MAb 2B2. The 2B2 heavy chain variable region (VH) and light chain variable region (VL) genes were cloned using PCR. The cloned VH gene coded for 123 amino acid residues and belonged to the subgroup III(D). The VL gene coded for 126 amino acid and belonged to the subgroup V. Collectively, these results will be used to develop an immunosuppressive chimeric or humanized anti-CD40L antibody.


[Comparison of Quality of Life of the Patients Three Months after Uniportal and Multiportal Thoracoscopic Lobectomy].
The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.


Substance Use and Mental Health Screening Within an Emergency Department-Based HIV Screening Program: Outcomes From 1 Year of Implementation.
The emergency department (ED) may be an optimal setting to screen for substance use disorders (SUDs) and co-occurring psychiatric disorders (CODs). We report on the frequency of problematic substance use and comorbid elevated mental health symptoms detected during a 1-year implementation period of an ED-based SUD/COD screening approach within an established ED HIV screening program. Patients (N = 1,924) were approached by dedicated HIV screening staff in an urban, Midwestern ED. Patients first completed measures assessing problematic alcohol (Alcohol Use Disorder Identification Test-Concise [AUDIT-C]) and substance use across 10 categories of substances (National Institute on Drug Abuse-Modified Alcohol, Smoking, and Substance Involvement Screening Test [NIDA-Modified ASSIST]). Patients with positive alcohol and/or substance use screens completed measures assessing symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and post-traumatic stress disorder (PTSD) (PTSD Checklist-Civilian [PCL-C]). Patients were predominantly male (60.3%) with a mean age of 38.1 years (SD = 13.0); most identified as White (50.8%) or Black (44.8%). A majority (58.5%) had a positive screen for problematic alcohol and/or other substance use. Of those with a positive substance use screen (n = 1,126), 47.0% had a positive screen on one or more of the mental health measures with 32.1% endorsing elevated depressive symptoms, 29.6% endorsing elevated PTSD-related symptoms, and 28.5% endorsing elevated anxiety symptoms. Among those receiving ED HIV screening, a majority endorsed problematic alcohol and/or other substance use and co-occurring elevated mental health symptoms. Substance use and mental health screening programs that can be integrated within other ED preventive services may enhance the identification of individuals in need of further assessment, referral, or linkage to substance use treatment services.


An evaluation of the nutrient intake of a group of elderly people attending a luncheon club.
A study was conducted to assess the nutrient intake of a group of 18 elderly men and women aged 67-85 years who attend a luncheon club in a North London Borough. Adequate intakes of most nutrients were demonstrated with the exception of zinc, although due to wide individual variation some people had intakes greatly below recommendations. The contribution of the luncheon club meal to the total diet varied widely between individuals. For the group, the difference between the mean energy and nutrient (except protein) intakes on luncheon club days and non-luncheon club weekdays was not statistically significant. However, for some individuals whose intakes of certain nutrients was low, e.g. vitamin C, it is probable that a greater contribution to the nutrients intake was obtained from the luncheon club meal than from meals consumed at home.


Current state of dialysis access management in Korea.
The prevalence rate and the incidence rate of hemodialysis and functioning kidney transplant recipients have continuously increased; on the contrary, those of peritoneal dialysis have continuously decreased since 2006. Dialysis patients have been getting older and have been maintained on dialysis longer. Diabetic nephropathy was the leading cause of end stage renal disease. The type of hemodialysis vascular access has been stable during the last 5 years (arteriovenous fistulas 76%, arteriovenous grafts 16%, central venous catheters 8% at 2016). Peritoneal dialysis catheter was mostly inserted surgically (67%), and swan neck straight tip peritoneal dialysis catheter was the most commonly used (48%). Vascular access was managed by radiologists and surgeons, and the management was fragmented among them in the past. However, since the nephrologists became interested in and knowledgeable about the vascular access, they began to play roles in vascular access management. Vascular access has been mostly created by vascular surgeons (≈60%); tunneled central venous hemodialysis catheter insertion and endovascular intervention such as percutaneous transluminal angioplasty (PTA) and thrombectomy have been mostly performed by radiologists (≈70%). Tunneled hemodialysis catheter insertion and endovascular intervention by nephrologists have slowly but consistently increased. Recently, the number of central venous hemodialysis catheter insertion has decreased, and tunneled hemodialysis catheter has been inserted more than non-tunneled hemodialysis catheter, indicating that vascular access has been created timely and the vascular access team has been educated about and following international guidelines.


Exquisite sensitivity of adrenocortical carcinomas to induction of ferroptosis.
Adrenocortical carcinomas (ACCs) are rare and highly malignant cancers associated with poor survival of patients. Currently, mitotane, a nonspecific derivative of the pesticide DDT (1,1-(dichlorobiphenyl)-2,2-dichloroethane), is used as the standard treatment, but its mechanism of action in ACCs remains elusive. Here we demonstrate that the human ACC NCI-H295R cell line is remarkably sensitive to induction of ferroptosis, while mitotane does not induce this iron-dependent mode of regulated necrosis. Supplementation with insulin, transferrin, and selenium (ITS) is commonly used to keep NCI-H295R cells in cell culture. We show that this supplementation prevents spontaneous ferroptosis, especially when it contains polyunsaturated fatty acids (PUFAs), such as linoleic acid. Inhibitors of apoptosis (zVAD, emricasan) do not prevent the mitotane-induced cell death but morphologically prevent membrane blebbing. The expression of glutathione peroxidase 4 (GPX4) in H295R cells, however, is significantly higher when compared to HT1080 fibrosarcoma cells, suggesting a role for ferroptosis. Direct inhibition of GPX4 in H295R cells led to high necrotic populations compared to control, while cotreatment with ferrostatin-1 (Fer-1) completely reverted ferroptosis. Interestingly, the analysis of public databases revealed that several key players of the ferroptosis pathway are hypermethylated and/or mutated in human ACCs. Finally, we also detected that growth hormone-releasing hormone (GHRH) antagonists, such as MIA602, kill H295R cells in a nonapoptotic manner. In summary, we found elevated expression of GPX4 and higher sensitivity to ferroptosis in ACCs. We hypothesize that instead of treatment with mitotane, human adrenocortical carcinomas may be much more sensitive to induction of ferroptosis.


Dietary folate, B vitamins, genetic susceptibility and progression to advanced nonexudative age-related macular degeneration with geographic atrophy: a prospective cohort study.
There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value. We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility. Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses. There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither folate nor any B vitamin was significantly associated with neovascular AMD. High folate intake was associated with a reduced risk of progression to GA. This relation could be modified by genetic susceptibility, particularly related to the C3 genotype. This trial was registered at clinicaltrials.gov as NCT00594672.


Pharmacokinetic and Drug Metabolism Properties of Novel Therapeutic Modalities.
The discovery and development of novel pharmaceutical therapies is rapidly transitioning from a small molecule-dominated focus to a more balanced portfolio consisting of small molecules, monoclonal antibodies, engineered proteins (modified endogenous proteins, bispecific antibodies, and fusion proteins), oligonucleotides, and gene-based therapies. This commentary, and the special issue as a whole, aims to highlight these emerging modalities and the efforts underway to better understand their unique pharmacokinetic and absorption, disposition, metabolism, and excretion (ADME) properties. The articles highlighted herein can be broadly grouped into those focusing on the ADME properties of novel therapeutics, those exploring targeted-delivery strategies, and finally, those discussing oligonucleotide therapies. It is also evident that whereas the field in general continues to progress toward new and more complex molecules, a significant amount of effort is still being placed on antibody-drug conjugates. As therapeutic molecules become increasingly complex, a parallel demand for advancements in experimental and analytical tools will become increasingly evident, both to increase the speed and efficiency of identifying safe and efficacious molecules and simultaneously decreasing our dependence on in vivo studies in preclinical species. The research and commentary included in this special issue will provide researchers, clinicians, and the patients we serve more options in the ongoing fight against grievous illnesses and unmet medical needs. SIGNIFICANCE STATEMENT: Recent trends in drug discovery and development suggest a shift away from a small molecule-dominated approach to a more balanced portfolio that includes small molecules, monoclonal antibodies, engineered proteins, and gene therapies. The research presented in this special issue of Drug Metabolism and Disposition will serve to highlight advancements in the understanding of the mechanisms that govern the pharmacokinetic and drug metabolism properties of the novel therapeutic modalities.


Validation of three-dimensional wound measurements using a novel 3D-WAM camera.
To monitor wound healing, it is essential to obtain accurate and reliable wound measurements. Various methods have been used to measure wound size including three-dimensional (3D) measurement devices enabling wound assessment from a volume perspective. However, the currently available methods are inaccurate, costly, or complicated to use. As a consequence, we have developed a 3D-wound assessment monitor (WAM) camera, which is able to measure wound size in three-dimension and to assess wound characteristics. The aim of the study was to assess the intrarater and interrater reliability of the 3D wound measurements using the 3D camera and to compare these with traditional measurement methods. Four raters measured 48 wounds using the 3D camera, digital imaging method (2D area), and gel injection into the wound cavity (volume). The data were analyzed using linear mixed effect model. Intraclass and interclass correlation coefficient (ICC) and Bland-Altman plots were used to assess intrarater and interrater reliability for the 3D camera and agreement between the methods. The Bland-Altman plots for intrarater reliability showed minor differences between the measurements, especially the 3D area and perimeter measurements. Moreover, ICCs were very high for both the intrarater and interrater reliability for the 2D area, 3D area, and perimeter measurements (ICCs > 0.99), although slightly lower for the volume measurements (ICC = 0.946-0.950). Finally, a high agreement was found between the 3D camera and the traditional methods (2D area and volume) assessed by narrow 95% prediction intervals and high ICCs above 0.97. In conclusion, the 3D-WAM camera is an accurate and reliable method, which is useful for several types of wounds. However, the volume measurements were primarily useful in large, deep wounds. Moreover, the 3D images are based on digital technology and therefore carry the possibility for use in remote settings.


[Effect of calcium, thrombin and nucleotides (ADP, cAMP, cGMP) on blood platelet glycolysis and energy metabolism].
It has been shown that ADP, thrombin, calcium, cAMP and cGMP induce changes in platelet metabolism. Aggregation inducers that inhibit the glycolytic enzymes decrease the content of pyruvate and ATP in platelets. The aggregation inhibitor, cAMP increases the activity of pyruvate kinase and the content of pyruvate and ATP in platelets. Cyclic AMP does not affect the activity of pyruvate kinase but raises the level of pyruvate and diminishes the content of ATP in platelets.


cAMP-stimulated cation cotransport in avian erythrocytes: inhibition by "loop" diuretics.
The effect of a series of diuretically active substituted 3-aminobenzoic acid derivatives and related compounds was investigated on a cyclic AMP-activated Na+-K+ cotransport system in avian erythrocytes. A good correlation between the diuretic potency of this class of "loop" diuretics in the dog and their inhibition of cation cotransport in turkey erythrocytes was found. Selected thiazide-type diuretics were found to be ineffective. The most active compound tested (3-benzylamino-4-phenylthio-5-sulfamoylbenzoic acid) had an effective dose50 of 4.6 x 10(-8) M in the avian system, and was about 5 times more potent than bumetanide and 500 times more potent than furosemide in this regard. The diuretics appear to interact directly with the cation transport system itself, and not with some antecedent step in the sequence of events from intracellular cAMP accumulation to stimulation of transport. The compounds tested did not appear to compete at Na+- or K+-binding sites on the transport system. The similarity in the structure-activity relationship of these agents in the avian erythrocyte and the kidney suggests that the avian erythrocyte may be a useful model for analysis both of the diuretic-sensitive transport system of the mammalian kidney, and of the molecular mechanism of loop diuretic action.


lncRNA FBXL19-AS1 regulates osteosarcoma cell proliferation, migration and invasion by sponging miR-346.
It was recently reported that lncRNA FBXL19 antisense RNA 1 (FBXL19-AS1) is a novel tumor-promoting RNA that contributes to tumor progression by sponging miRNAs. However, the expression and function of FBXL19-AS1 in osteosarcoma (OS) have not been investigated. Cell proliferation was assessed by the CCK-8 and colony formation assays, while cell migration and invasion were assessed using wound healing and transwell invasion assays, respectively. Quantitative reverse transcriptase PCR and immunofluorescence were used to detect the level and subcellular localization of FBXL19-AS1 expression. Interactions between miRNAs and FBXL19-AS1 were determined using luciferase reporter assays. Finally, in vivo experiments were performed to assess tumor formation. We first showed that lncRNA FBXL19-AS1 was upregulated in OS tissues and cell lines. In vitro experiments showed that FBXL19-AS1 promoted OS cell proliferation, migration, and invasion. Inhibiting miR-346 led to a significant upregulation of FBXL19-AS1, suggesting FBXL19-AS1 was negatively regulated by miR-346, which was further confirmed by the inverse correlation between FBXL19-AS1 and miR-346 expression in OS patient specimens. Furthermore, we proved that miR-346 could directly target FBXL19-AS1 through luciferase assays, suggesting FBXL19-AS1 could sponge miR-346. Additionally, inhibiting miR-346 blocked the effects of silencing FBXL19-AS1 on proliferation, migration, and invasion. Moreover, inhibiting FBXL19-AS1 significantly promoted the malignancy of MG63 and 143B cells in vivo. We validated FBXL19-AS1 as a novel oncogenic lncRNA and demonstrated the molecular mechanism through which it promotes OS progression. This work advances our understanding of the clinical significance of this RNA species.


A multicentric, randomized, comparative clinical trial to evaluate the efficacy and safety of S-etodolac in the treatment of osteoarthritis in Indian patients.
To compare the efficacy and safety of S-etodolac with etodolac in the treatment of osteoarthritis in Indian patients. This was a double-blind, multicentric, comparative clinical trial conducted in 108 Indian patients with osteoarthritis. All patients received either S-etodolac ER 300 mg or etodolac ER 600 mg tablets once daily. Assessment was done on the basis of WOMAC score and VAS pain score, patient's and physician's global assessment of the arthritic condition. All patients were evaluated after every 2 weeks for 4 weeks for efficacy and safety variables. Total 49 patients in the test group and 52 patients in the reference group completed the study. There was significant improvement (p < 0.0001) in all WOMAC subscales (pain, stiffness and physical function), WOMAC total score and VAS pain score in both the groups. Patient's and physician's global assessment of the arthritic condition also improved significantly (p < 0.0001). All patients showed improvement in WOMAC and VAS pain score by (3) 20%. There was no significant difference between the groups for the efficacy parameters. The adverse events reported were few and no serious adverse events were reported. Total 5 patients in S-etodolac group and 2 patients in etodolac group dropped out of the study. Only 1 patient dropped out because of the side effects of burning sensation, palpitations and anxiety in the test group. The present study has established the efficacy, tolerability and safety of S-etodolac extended release tablets in the treatment of osteoarthritis in Indian patients.


Sauna-induced acceleration in insulin absorption from subcutaneous injection site.
The effect of the Finnish sauna on insulin absorption from a subcutaneous injection site was examined in eight insulin-dependent diabetic patients by measuring externally the disappearance rate of 125I-labelled rapid-acting insulin. The sauna (twice for 25 minutes at 85 degrees C) accelerated insulin absorption by 110% as compared with room temperature (p < 0.01). After the sauna blood glucose concentrations were 3.0-3.3 mmol/1 (54.1-59.5 mg/100 ml) lower than on the control day (p < 0.05). The fall in blood glucose values was proportional to the increased rate of insulin absorption (r = 0.30; p < 0.01). The hypoglycaemic effect of a sauna in insulin-treated diabetics is clearly at least partly due to enhanced insulin absorption from the injection site. Such an effect might be prevented by taking a snack or reducing the insulin dose.


Biochemical properties, homology, and genetic variation of Drosophila "nonspecific" esterases.
The biochemical properties and tissue distribution of two major, soluble "nonspecific" esterases have been studied in Drosophila melanogaster, D. pseudoobscura, and related species. The "alpha-like" activity is due to a monomer enzyme (MW congruent to 60 kd) having a nonspecific tissue distribution, which was inhibited by p-hydroxymercuribenzoate (5 X 10(-4)M) plus eserine (1 X 10(-5)M) and was relatively unstable during polyacrylamide gel electrophoresis. Electrophoretograms of this enzyme could be enhanced by treating gels with beta-mercaptoethanol before staining. This procedure allowed the identification of a new alpha-esterase (Est-4) in D. pseudoobscura. The "beta-like" esterase activity (EC 184.108.40.206) is due to a dimer (MW congruent to 120 kd) in most Drosophila species. D. melanogaster and its siblings (D. simulans and D. mauritiana) were exceptions in which this enzyme had an unusual tissue distribution (increased activity in the male reproductive system) and was a monomer (MW congruent to 60 kd). Differences in the genetic variability of these esterases are discussed and interpreted by a population expansion model rather than by differences in biochemical properties of enzyme forms.


A user-driven treadmill control scheme for simulating overground locomotion.
Treadmill-based locomotor training should simulate overground walking as closely as possible for optimal skill transfer. The constant speed of a standard treadmill encourages automaticity rather than engagement and fails to simulate the variable speeds encountered during real-world walking. To address this limitation, this paper proposes a user-driven treadmill velocity control scheme that allows the user to experience natural fluctuations in walking velocity with minimal unwanted inertial force due to acceleration/deceleration of the treadmill belt. A smart estimation limiter in the scheme effectively attenuates the inertial force during velocity changes. The proposed scheme requires measurement of pelvic and swing foot motions, and is developed for a treadmill of typical belt length (1.5 m). The proposed scheme is quantitatively evaluated here with four healthy subjects by comparing it with the most advanced control scheme identified in the literature.


Fluoroscopy-assisted dual-catheter thromboembolectomy: a new technique useful in patients with embolization to arteries of disproportionate diameters.
Distal embolization is a complication of aortoiliac aneurysm repair. Fluoroscopy-assisted catheter thromboembolectomy is useful in removing popliteal and tibial emboli from the femoral approach. Concomitant presence of aortoiliac and popliteal aneurysms, a known association, may present a difficult challenge to embolus extraction. Currently available embolectomy catheters large enough for thrombus extraction from a popliteal aneurysm are too large for safe tibial artery cannulation, and tibial balloon catheters cannot be enlarged sufficiently to transfer the thrombus through the aneurysmal popliteal segment. We treated a patient who embolized to his popliteal aneurysm and distal tibial circulation following aortoiliac aneurysm repair. A fluoroscopy-assisted dual-catheter technique was used to extract the thrombus through the femoral approach, eliminating the need for direct popliteal or tibial exploration. This technique uses two balloon catheters of graduated size, maneuvered concurrently under fluoroscopic guidance into the tibial and popliteal circulation. The smaller tibial catheter is inflated, and thrombus is withdrawn into the popliteal segment. The larger popliteal balloon catheter is then inflated distal to the smaller catheter, and both catheters are withdrawn simultaneously to deliver the clot through the femoral arteriotomy. This technique can be useful for successful balloon catheter extraction of thrombus via remote access, in an arterial system with variable diameter, eliminating the need for direct popliteal or tibial exploration.


Self-reported financial conflicts of interest during scientific presentations in emergency medicine.
This study was a review of the scientific abstracts presented at a national conference for the required conflict of interest (COI) disclosure both before the meeting and during presentation. All presenters were given specific instructions regarding COI reporting at the time of abstract acceptance. All poster presentations were required to have a COI statement. Three physicians using standardized data abstraction forms reviewed abstracts accepted for poster presentation at the 2010 annual meeting of the Society for Academic Emergency Medicine (SAEM). Posters were reviewed for the presence of a required COI disclosure statement, and these results were compared to the mandatory continuing medical education (CME) disclosure form that was sent by the presenters to the SAEM central office before the meeting. There were 412 posters accepted for presentation at the 2010 SAEM annual meeting. The reviewers observed 382 (93%) of the total posters for the conference. Sixty-nine abstracts (18%) reported a COI. Only 26 (38%) of these were actually reported to the SAEM office on the CME disclosure form before the meeting; the remaining 62% were found on the poster alone. COI that were reported on the CME disclosure form were found on the poster 46% of the time. The remaining posters without a COI actually displayed the mandatory disclosure statement only 14% of the time. This review of presentations at a national meeting found a lack of compliance with printed guidelines for COI disclosure during scientific presentation. Efforts to increase uniformity and clarity may result in increased compliance.


Instrumentation for automated and quantitative low temperature compaction and sintering.
This report describes the design, operation, and capabilities of a semiautomated uniaxial press with in situ measurement of platen displacements designed to facilitate, understand, and improve compaction and densification of particulate materials contained in conventional metal dies under modest temperatures. While not exclusive to one implementation, the instrumentation is particularly well-suited to study cold sintering. The instrumentation shares similarities to dilatometry, given the ability to monitor pellet compaction, and calorimetry, given the ability to monitor phase transitions by their molar volume signatures. Pursuant to these similarities, we refer to this device as a sinterometer. A critical benefit to this automation is a new ability to conduct experiments unattended for indefinite amounts of time under constant pressure while collecting quantitative data. We demonstrate densification profile computation (i.e., sintegram) using this instrument, including methods to account for the thermal expansion background of the metal die. A set of examples are provided where this stable and long-term data collection allows one to identify densification mechanisms and phase transformations that occur during cold sintering, which would be extremely time consuming, or impossible, to extract using a conventional, manual press.


A graduate course in work site health promotion for occupational health practitioners.
This paper describes the rationale, teaching strategies, outcomes, and a 6-month follow-up of an academic course in work site health promotion, in which 35 occupational health practitioners participated. The one-semester course was part of the Masters in Science program in occupational health at the Tel-Aviv University Medical School. The primary goals of the study were to teach the theoretical bases of work site health promotion and their application to specific health needs, and to train better role models for employees. The primary teaching strategies were: (1) facilitation of experiential learning, by encouraging students to undergo health screening and then engage in a personal health promotion plan; (2) use of health promotion experts as guest teachers; and (3) an increase in formal knowledge through formal lectures and background reading. At the time of follow-up, most of the students were still adhering to their plans and maintaining much of their health promotion achievements. Additional outcomes included increased awareness of health risks and health promotion issues, and positions as role models in the private and professional domains. The primary barrier to adherence was low frustration tolerance, which can be regarded as the major challenge to health promotion programs and courses. It is suggested that the course format is an effective means of educating health promoters.


Rapid Sentinel Surveillance for COVID-19 - Santa Clara County, California, March 2020.
On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.


Transcriptional Profiling Reveals Differential Gene Expression of Amur Ide (Leuciscus waleckii) during Spawning Migration.
Amur ide (Leuciscus waleckii), an important aquaculture species, inhabits neutral freshwater but can tolerate high salinity or alkalinity. As an extreme example, the population in Dali Nor lake inhabits alkalized soda water permanently, and migrates from alkaline water to neutral freshwater to spawn. In this study, we performed comparative transcriptome profiling study on the livers of Amur ide to interrogate the expression differences between the population that permanently inhabit freshwater in Ganggeng Nor lake (FW) and the spawning population that recently migrated from alkaline water into freshwater (SM). A total of 637,234,880 reads were generated, resulting in 53,440 assembled contigs that were used as reference sequences. Comparisons of these transcriptome files revealed 444 unigenes with significant differential expression (p-value ≤ 0.01, fold-change ≥ 2), including 246 genes that were up-regulated in SM and 198 genes that were up-regulated in FW. The gene ontology (GO) enrichment analysis and KEGG pathway analysis indicated that the mTOR signaling pathway, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, and oxidative phosphorylation were highly likely to affect physiological changes during spawning migration. Overall, this study demonstrates that transcriptome changes played a role in Amur ide spawning migration. These results provide a foundation for further analyses on the physiological and molecular mechanisms underlying Amur ide spawning migration.