High-sensitivity and high-resolution therapeutic antibody charge variant and impurity characterization by microfluidic native capillary electrophoresis-mass spectrometry.
Therapeutic antibodies are a major class of pharmaceutical drugs used to treat a wide variety of diseases. They have several advantages including the high specificity and binding affinity to their molecular targets, and generally low immunotoxicity and mild adverse effects. The characterization of therapeutic antibodies is crucial to ensure drug efficacy and safety. Charge variant analysis can be used to examine the charge variant forms of therapeutic antibodies, which may reflect modifications that impact the drug quality. Native capillary electrophoresis-mass spectrometry (nCE-MS) analysis by an integrated ZipChip CE-MS system is an alternative and complementary method to cation-exchange chromatography and imaged capillary isoelectric focusing to support the characterization of charge variants. In this study, we performed nCE-MS analysis to evaluate the charge variants and impurities in therapeutic antibodies including immunoglobin G (IgG) monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and alternative formats such as therapeutic antibodies with addition or removal of antigen-binding domain. With the ZipChip CE-MS system, high-resolution charge variant separation was achieved for different types of therapeutic antibodies. Moreover, ZipChip nCE-MS analysis enabled high-sensitivity detection and identification of species with low abundance, including proteolytic cleavage and fragmentation in mAb, monospecific mAb impurities in bsAb, and O-glycosylation in alternative formats to support biopharmaceutical development and investigations.


Automated detection and classification of counterfeit banknotes using quantitative features captured by spectral-domain optical coherence tomography.
Counterfeiting of banknotes is still a severe crime problem in many countries. One of the most significant issue for solving the crime is to classify the counterfeit types and identify the sources. Most of the current methods to classify counterfeit banknotes rely on manual examination that is time-consuming and labor-intensive. Moreover, these methods only detect surface features which can be easily imitated through advanced printing technology. In this study, an automated method based on optical coherence tomography (OCT) and machine-learning algorithms was proposed to classify different types of banknotes based on the internal features. A spectral-domain OCT (SD-OCT) system was employed for sub-surface imaging and quantitative assessment of banknotes. A total of 29 Chinese 100-Yuan banknotes were collected, in which 4 of them were real and 25 of them were counterfeiting by three different printing processes. Each banknote was imaged 10 times in 3 distinct regions, which resulted in a dataset of 290 samples. Each sample was characterized by extracting 2 A-scan (OCT signal intensity along depth) based features and 14B-scan (cross-sectional OCT images) based features. Several machine-learning models, including logistic regression (LR), support vector machines (SVM), K-nearest neighbor (KNN) and random forest (RF), were built and optimized as the classifiers that were trained using 203 samples and applied to predict 87 testing samples. The best performance was achieved by SVM classifier in which the sensitivity of 96.55% and specificity of 98.85% were obtained in discriminating between authentic and counterfeit banknotes, and the sensitivity of 94.67% and specificity of 98.22% were obtained in predicting the types of counterfeit banknotes. These classifiers were also evaluated using the receiver operating characteristic (ROC) curves. To the best of our knowledge, this is the first study where A-scan and B-scan derived features from OCT images have been used for the detection and classification of different types of counterfeit banknotes.


A confidence interval for mutant frequency in assays using microtiter wells.
Previous attempts to derive a confidence interval for the estimated mutant fraction in assays using microtiter wells have not considered the variance introduced by the early growth and dilution steps. We derive a confidence interval that includes these sources of variability.


Serum cholesterol levels and mood symptoms in the postpartum period.
During pregnancy, the total serum cholesterol concentration rises up to 43%, followed by a rapid fall after delivery. Mild depressive symptoms ('postpartum blues') are a common complication of the puerperium and affect 30-85% of women in the early postpartum period. Based on these observations, it has been suggested that the sudden fall in cholesterol levels after delivery could serve as a 'natural model' to test the suggested association between cholesterol and mood. The present study was designed to expand the database concerning the association between cholesterol levels and mood in the postpartum period and to address some methodological problems raised by previous studies. Forty-seven healthy primiparous women were interviewed with a structured clinical interview on two occasions: during late pregnancy (median: day -20 before the expected delivery) and during the early postpartum period (median: day 32 after delivery). On both occasions, serum concentrations of total and HDL cholesterol were measured and mood symptoms were assessed with the state form of Spielberger's State-Trait Anxiety Index (STAI), the state form of the State-Trait Anger Scale (STAS), and the Beck Depression Inventory (BDI). We found significant, albeit moderate, relationships between serum cholesterol levels and mood symptoms in the postpartum period that were not present during late pregnancy. Lower postpartum levels of total cholesterol were associated with symptoms of anxiety (r=-0.30, P=0.04), anger/hostility (r=-0.31, P=0.04), and depression (r=-0.35, P=0.02), and lower postpartum levels of HDL cholesterol were associated with symptoms of anxiety (r=-0.34, P=0.02). This study confirms that the physiological fall in blood lipids in the postpartum period can be a useful model to test the relationship between serum cholesterol levels and mood.


Assignment of the human gene for enolase 1 to region pter in equilibrium p36 of chromosome 1.
Somatic cell hybrids between mouse cells and human cells carrying a reciprocal translocation between chromosomes 1 and 7 were tested for the expression of human enolase 1 (ENO1) by starch-gel electrophoresis. The results indicated that the gene for human enolase 1 can be assigned to the region p36 in equilibrium pter of human chromosome 1.


Impact of aging and gender on the Ig-containing cell profile of the lacrimal gland.
The present study investigated the influence of age and gender on the number of IgA- and IgM-containing cells in the lacrimal gland. Tissues were obtained from male and female rats at 0.2 (infant), 0.6 (pre-pubertal), 1.3 (pubertal), 3 (adult), 8 (mid-life) and 17 (senescent) months of age, then processed for immunofluorescence microscopy. No IgA-containing cells could be detected in lacrimal glands from infant rats, but a significant accumulation had occurred by 0.6 months of age. The extent of this increase was gender-dependent: tissues from male rats had significantly higher IgA-positive cell densities than those of females. After 0.6 months of age, no further variations in the density of IgA-containing lymphocytes were observed in female gland. In contrast, male glands exhibited marked fluctuations in the density of IgA-containing lymphocytes during the time period spanning puberty (0.6----3 months). Of interest, the frequency distribution of IgA-containing cells in tissue sections was not uniform in rats older than 0.2 months. Correction of cell densities for age-related elevations in lacrimal gland weight demonstrated that the total accumulation of IgA-containing cells was both age- and gender-related. Highest cell numbers were attained at 3 months in females and 3 and 17 months in males. Moreover, at all assessed ages, the total IgA-containing cell number in glands of males was greater than, or equal to, that in tissues of females.(ABSTRACT TRUNCATED AT 250 WORDS)


Does the inclusive disjunction really mean the conjunction of possibilities?
There is an ongoing dispute in the psychology of reasoning about how people interpret disjunctions, p or q. In the original mental models theory (MMT1) people interpret p or q as the disjunction of three possibilities (possibly p¬q, or possibly ¬pq, or possibly pq, where "¬" = not). p or q is true if one disjunct is actually true. In a recent revision of mental models theory (MMT2), people interpret p or q as a conjunction of the three possibilities, and they treat it as true only if each is possible and ¬p¬q is impossible. Two experiments investigated possibility and truth judgments about disjunctions given sets consisting of one or more of the four cases (p¬q, ¬pq, pq, and ¬p¬q). The results showed that in both possibility and truth judgments, participants' interpretations of disjunctions were only consistent with MMT1. Inclusive disjunctions imply the disjunction of the three possibilities, and they are true when one of the three cases (p¬q, ¬pq, and pq) is actual. These findings support MMT1, but not MMT2. In conclusion, the revised mental models theory may be unnecessary for disjunctions.


Pleuroperitoneal communication in a patient with right pleural effusion and ascites diagnosed by technetium-99m sulfur colloid imaging.
A 55-year-old man with an 11-year history of intermittent right pleural effusions had continued fevers and a large right transudative pleural effusion. Minimal ascites was noted by ultrasound examination. A communication between the thorax and intraperitoneal cavity was established by radionuclide examination of the chest and abdomen. Tc-99m sulfur colloid was injected into the peritoneal cavity, and imaging at 1 and 4.5 hours confirmed passage from the peritoneal to the pleural cavity. Repeated attempts to sclerose the pleural cavity failed to decrease the transudative accumulations. The patient was subsequently treated with the placement of a LeVeen shunt.


Bioactive Bianthraquinones and Meroterpenoids from a Marine-Derived Stemphylium sp. Fungus.
Three new bianthraquinones, alterporriol Z1-Z3 (1-3), along with three known compounds of the same structural class, were isolated from the culture broth of a marine-derived Stemphylium sp. fungus. Based upon the results of spectroscopic analyses and ECD measurements, the structures of new compounds were determined to be the 6-6'- (1 and 2) and 1-5'- (3) C-C connected pseudo-dimeric anthraquinones, respectively. Three new meroterpenoids, tricycloalterfurenes E-G (7-9), isolated together with the bianthraquinones from the same fungal culture broth, were structurally elucidated by combined spectroscopic methods. The relative and absolute configurations of these meroterpenoids were determined by modified Mosher's, phenylglycine methyl ester (PGME), and computational methods. The bianthraquinones significantly inhibited nitric oxide (NO) production and suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW 264.7 cells.


A Genome-Wide Survey of MATE Transporters in Brassicaceae and Unveiling Their Expression Profiles under Abiotic Stress in Rapeseed.
The multidrug and toxic compound extrusion (MATE) protein family is important in the export of toxins and other substrates, but detailed information on this family in the Brassicaceae has not yet been reported compared to Arabidopsis thaliana. In this study, we identified 57, 124, 81, 85, 130, and 79 MATE genes in A. thaliana, Brassica napus, Brassica oleracea, Brassica rapa, Brassica juncea, and Brassica nigra, respectively, which were unevenly distributed on chromosomes owing to both tandem and segmental duplication events. Phylogenetic analysis showed that these genes could be classified into four subgroups, shared high similarity and conservation within each group, and have evolved mainly through purifying selection. Furthermore, numerous B. napusMATE genes showed differential expression between tissues and developmental stages and between plants treated with heavy metals or hormones and untreated control plants. This differential expression was especially pronounced for the Group 2 and 3 BnaMATE genes, indicating that they may play important roles in stress tolerance and hormone induction. Our results provide a valuable foundation for the functional dissection of the different BnaMATE homologs in B. napus and its parental lines, as well as for the breeding of more stress-tolerant B. napus genotypes.


Identifying Human Trafficking Victims on a Psychiatry Inpatient Service: a Case Series.
Human trafficking is a serious and prevalent human rights violation that closely intersects with mental health. Limited empirical attention has been paid to the presentations and identification of trafficking victims in psychiatric settings. The primary goal of this paper is to describe the varied presentations of trafficking victims on an urban inpatient psychiatric unit. A literature review was conducted to identify relevant empirical articles to inform our examination of cases. Adult inpatient cases meeting criteria for known or possible human trafficking were systematically identified and illustrative cases were described. Six cases were identified including one male and five females. Two had been labor trafficked and four were suspected or confirmed to have been sex trafficked. The cases demonstrated a tremendous diversity of demographic and psychiatric identifying factors. These cases indicate the importance of routinely screening for trafficking victims in inpatient psychiatry settings. Identification of cases is a requisite step in providing informed and evidence-based treatments and enabling the secondary prevention of re-exploitation. Additional research is warranted given the limited current empirical research on this topic area.


An investigation of the presence of Escherichia coli O149:K91:F4 on pig farms in southern Ontario and the use of antimicrobials and risk factors associated with the presence of this serogroup.
Prevalence, causative factors, treatment, and preventative measures for O149:K91:F4 Escherichia coli infection of postweaning pigs was determined by using a cross-sectional study including 70 farms in Ontario. Surveys were distributed and samples cultured bacteriologically, resulting in 30% of farms testing positive to E. coli 0149:K91:F4. Possible causative factors, such as housing or nutrition, were not significantly different between positive and negative farms. Use of injectable antibiotics (P = 0.05) and zinc oxide (P = 0.003) was higher on E. coli O149:K91:K88 (F4)-positive farms. A higher level of biosecurity and the presence of other diseases may be associated with an increased risk of isolating E. coli O149:K91:F4 from weanling pigs.


The effect of plateletpheresis on the Fenwal CS-3000 on donor platelet counts.
To evaluate the risk of significant plateletpheresis-induced thrombocytopenia in normal volunteer donors undergoing plateletpheresis less frequently than every 56 days and to help understand factors influencing platelet yield in these donors, pre- and postapheresis platelet counts (X 10(3)/microliter) and platelet yields were analyzed from 916 plateletpheresis procedures (Fenwal CS-3000) on 607 donors (405 men, 202 women). The mean preapheresis platelet count was 265 +/- 59 (SD) (range 155-650) (men 256 +/- 55 [170-444]; women 284 +/- 65 [155-650]; P less than .001, t-test). After an average platelet yield of 4.08 X 10(11), the mean postplatelet count was 185 +/- 46 (range 72-420) (men 184 +/- 42 [80-345]; women 194 +/- 52 [72-500]; P less than 0.1). The percent decrease in platelet count (mean 29.4 +/- 13, range -28.1-65.5) had positive correlations with platelet yield (P less than .01, r = 0.10), predonation platelet count (P less than .001, r = 0.29), and age (P less than .01, r = .10) and a negative correlation with weight (P less than .001, r = 0.18) Both the percent decrease and platelet yield were significantly higher in women than in men (P less than .001, t-test), and platelet yield was best predicted by preapheresis platelet count in both sexes (r = 0.65). The effects of plateletpheresis on donor platelet count thus vary widely among donors. Although a decrease of greater than 50% was not a rare event (5.9% of all procedures), in only three instances (0.3%) was the actual postapheresis platelet count below 100 (72, 94, 95). Thus, plateletpheresis in normal donors appears unlikely to produce clinically significant thrombocytopenia immediately after apheresis.


Program evaluation in a rural community mental health center.
Can a rural community mental health center with limited resources meet the federal guidelines for program evaluation? This case example shows that a rural center can comply with the guidelines through evaluation activities tailored to its special needs and small size.


Delayed myocardial ischemia following the cessation of sympathetic stimulation.
A phenomenon entitled "delayed myocardial ischemia" has been described, in which there is a significant degree of coronary malperfusion following the cessation of behavioral stress. The primary objective of the present study was to develop a model for the delayed ischemic response in anesthetized animals to gain insights into the underlying mechanisms. In 15 morphine and chloralose-anesthetized dogs, a moderate degree of stenosis was applied to the left circumflex coronary artery by means of a toroidal balloon occluder. The pulsed Doppler technique was used to monitor coronary flow. After baseline data were obtained, the left stellate ganglion was stimulated for 30 seconds. Heart rate increased (63%), as did systemic blood pressure (41%) and flow in the left circumflex artery (47%). These parameters rapidly returned to control levels when stimulation was terminated. Forty-five to 90 seconds later, coronary flow decreased by 65% and coronary vascular resistance increased by 45%. These hemodynamic changes were accompanied by ECG abnormalities indicative of regional myocardial ischemia. The delayed ischemic response could be prevented by pretreatment with either nifedipine (20 micrograms/kg) or prazosin (0.3 mg/kg). These data indicate that the primary mechanism for the delayed ischemic response is alpha-adrenergically mediated contraction of the smooth muscle in the coronary artery wall.


Recent changes in UK medical law: implications for radiologists.
Since Lord Woolf declared in 2001 that the courts have been excessively deferential to the medical profession, there has been an incremental series of changes to the law concerning medical negligence. The most substantial changes concern consent, but significant change has also appeared regarding the concept of causation. This article reviews these changes, and points out areas of direct relevance to diagnostic and interventional radiology.


The glucose permease of Bacillus subtilis is a single polypeptide chain that functions to energize the sucrose permease.
Biochemical, immunological, and sequence analyses demonstrated that the glucose permease of Bacillus subtilis, the glucose-specific Enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system, is a single polypeptide chain with a C-terminal Enzyme III-like domain. A flexible hydrophilic linker, similar in length and amino acid composition to linkers previously identified in other regulatory or sensory transducing proteins, functions to tether the Enzyme IIIGlc-like domain of the protein to the membrane-embedded Enzyme IIGlc. Evidence is presented demonstrating that the Enzyme IIIGlc-like domain of the glucose permease plays a dual role and functions in the transport and phosphorylation of both glucose and sucrose. The sucrose permease appears to lack a sucrose-specific Enzyme III-like domain or a separate, soluble IIIScr protein. Enzyme IIScr was capable of utilizing the IIIGlc-like domain of the glucose permease regardless of whether the IIIGlc polypeptide was provided as a purified, soluble protein, as a membrane-bound protein within the same membrane as Enzyme IIScr, or as a membrane-bound protein within membrane fragments different from those bearing Enzyme IIScr. These observations suggest that the IIIGlc-like domain is an autonomous structural unit that assumes a conformation independent of the hydrophobic, N-terminal intramembranal domain of Enzyme IIGlc. Preferential uptake and phosphorylation of glucose over sucrose has been demonstrated by both in vivo transport studies and in vitro phosphorylation assays. Addition of the purified IIIGlc-like domain strongly stimulated the phosphorylation of sucrose, but not that of glucose, in phosphorylation assays that contained the two sugars simultaneously. The results suggest that the preferential uptake of glucose over sucrose is determined by competition of the corresponding sugar-specific permeases for the common P approximately IIIGlc/Scr domain.


Learning by looking: Infants' social looking behavior across the transition from crawling to walking.
This study investigated how infants gather information about their environment through looking and how that changes with increases in motor skills. In Experiment 1, 9.5- and 14-month-olds participated in a 10-min free play session with both a stranger and ambiguous toys present. There was a significant developmental progression from passive to active social engagement, as evidenced by younger infants watching others communicate more and older infants making more bids for social interaction. Experiment 2 examined longitudinally the impact of age and walking onset on this progression. The transition to independent walking marked significant changes in how often infants watched others communicate and made active bids for social interaction. Results suggest that infants transition from passive observers as crawlers to active participants in their social environment with the onset of walking.


Introduction to the role of oxygen radicals in myocardial ischemia and infarction.
There has been considerable interest over the past several years concerning the role of oxygen radicals in myocardial ischemia-reperfusion injury. The purpose of the following symposium will be to review recent advances in the understanding of oxygen free radical damage to the heart. Included in the symposium are descriptions of the biochemistry of free radicals and evidence of their direct toxic effects on the heart, as well as discussions concerning the effect of oxygen free radical scavengers on myocardial infarct size, the stunned myocardium, and cardiac preservation during surgery.


Acute liver failure.
ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation.


Comparison of clinical and radiological outcomes of local morselized bone grafts and structural iliac bone grafts in the treatment of lumbar tuberculosis with posterior-only surgery.
Many surgeons have reported results similar to those of anterior debridement and bone grafting in treating spinal tuberculosis in the lumbar region using only a posterior approach. However, there is still no consensus regarding bone graft methods. This study aims to compare the clinical and radiological outcomes of morselized versus structural iliac bone grafts in the treatment of lumbar tuberculosis via one-stage posterior surgery. A retrospective study was performed with 82 patients with lumbar tuberculosis who had undergone posterior-only debridement, bone grafting, and instrumentation between January 2014 and June 2018. Morselized bone grafts were used in 43 patients, whereas structural iliac bone grafts were used in 39 patients. The clinical data and imaging results of the patients were compared between the two groups to evaluate the clinical effects of the two types of grafts. The operation time, blood loss and hospital stay values in the morselized bone group were significantly lower than those in the structural iliac bone group (p < 0.05). No significant differences were observed with respect to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Cobb angle, or improvement of neurological function between the two groups. The VAS pain scores for low back and leg pain decreased significantly after the operation (p < 0.05). However, postoperatively, the VAS score was higher in the structural iliac bone group than in the morselized bone group, and there was no significant difference at the last follow-up between the two groups (p > 0.05). Bone fusion was achieved in 41 patients (95%) in the morselized bone group and 38 patients (97%) in the structural iliac bone group. There was no significant difference between the fusion rates of the two groups (p > 0.05). The two graft techniques achieved comparable clinical outcomes in lumbar spinal tuberculosis treatment. However, the morselized bone graft was more beneficial in terms of reducing surgical trauma and postoperative complications.


Electron microscopic visualization of DNA single strand breaks.
DNA single strand breaks (ssb) have been induced in FLC/C cells in culture. They have been visualized in the electron microscope after decoration with biotin-avidin-ferritin complexes and spreading as monomolecular mixed films. This allowed one to determine the average number of decorated ssbs per unit of DNA length applying straight-forward and simple evaluation methods. This method has been used to investigate the DNA alterations by benzo[a]pyrene (B[a]P) on FLC/C culture cells. Thus a B[a]P-DNA damage curve can be constructed as a regression with a correlation coefficient of r = 0.97, while its isomer benzo[e]pyrene (B[e]P) known to have only low mutagenicity under the same experimental conditions is virtually without effect. The method has further informational potential regarding damage distribution and repair of DNA.


Comparison of pre-cryopreserved and post-thaw-and-wash-nucleated cell count on major outcomes following unrelated cord blood transplant in children.
Engraftment and OS after umbilical CBT is highly dependent on the TNC. The contribution of the wash step to cell loss and ultimately the dose of cells available for transplant is not well described. To investigate the amount of cell loss after washing and its impact on major outcomes compared to pre-cryopreserved TNC, we analyzed data from patients prospectively enrolled on a National Heart, Lung and Blood Institute sponsored cord blood transplant study between 1999 and 2003. There were 310 patients ≤18 yr of age with malignant (N = 218) or non-malignant (N = 92) disease enrolled on this trial. Only single CBU were used. All CBU were thawed and washed using an identical process. The median TNC after thawing and washing (PTW) was 5.43 × 10(7) /kg (79% recovery of cells). The cumulative incidence of neutrophil engraftment was significantly higher in patients receiving a PTW TNC ≥2.5 × 10(7) /kg (p = 0.01). The cumulative incidence of TRM was higher among patients receiving post-thaw-and-wash TNC <2.5 × 10(7) /kg (p = 0.039). In conclusion, receiving a PTW TNC of <2.5 × 10(7) /kg resulted in worse neutrophil engraftment and increased transplant-related mortality compared to a PTW TNC of ≥2.5 × 10(7) /kg.


Peer group training of pragmatic skills in adolescents with acquired brain injury.
To empirically evaluate a method of treating adolescents with cognitive communication disorders, including pragmatic deficits, secondary to acquired brain injury (ABI) in a group setting by objectively measuring outcomes before treatment and immediately after treatment and at 6 months posttreatment. A before-after trial with follow-up in a consecutive sample, with no control group. Inpatient and outpatient pediatric rehabilitation center. Adolescents who demonstrated pragmatic deficits and scored a rating of 3 or less on each subdomain of the Rehabilitation Institute of Chicago Rating Scale of Pragmatic Communication Skills (RICE-RSPCS) were eligible for the study. Eight subjects were recruited into the study, and two subjects were lost to follow-up. Thus, six of the eight completed the study. RICE-RSPCS, Communication Performance Scale (CPS). Clinically relevant and statistically significant (P <.01) changes occurred during the treatment and were maintained at follow-up for the four RICE-RSPCS subscales and the CPS. These results suggest that the potential and often typical long-term pragmatic and subsequent social difficulties associated with ABI can possibly be lessened through effective intervention.


Neighbourhood Deprivation, Individual-Level and Familial-Level Socio-demographic Factors and Risk of Congenital Heart Disease: A Nationwide Study from Sweden.
The purpose of the study is to examine whether there is an association between neighbourhood deprivation and incidence of congenital heart disease (CHD), after accounting for family- and individual-level potential confounders. All children aged 0 to 11 years and living in Sweden (n = 748,951) were followed between January 1, 2000 and December 31, 2010. Data were analysed by multilevel logistic regression, with family- and individual-level characteristics at the first level and level of neighbourhood deprivation at the second level. During the study period, among a total of 748,951 children, 1499 (0.2%) were hospitalised with CHD. Age-adjusted cumulative hospitalisation rates for CHD increased with increasing level of neighbourhood deprivation. In the study population, 1.8 per 1000 and 2.2 per 1000 children in the least and most deprived neighbourhoods, respectively, were hospitalised with CHD. The incidence of hospitalisation for CHD increased with increasing neighbourhood-level deprivation across all family and individual-level socio-demographic categories. The odds ratio (OR) for hospitalisation for CHD for those living in high-deprivation neighbourhoods versus those living in low-deprivation neighbourhoods was 1.23 (95% confidence interval (CI) = 1.04-1.46). In the full model, which took account for age, paternal and maternal individual-level socio-economic characteristics, comorbidities (e.g. maternal type 2 diabetes, OR = 3.03; maternal hypertension, OR = 2.01), and family history of CHD (OR = 3.27), the odds of CHD were slightly attenuated but did not remain significant in the most deprived neighbourhoods (OR = 1.20, 95% CI = 0.99-1.45, p = 0.057). This study is the largest so far on neighbourhood influences on CHD, and the results suggest that deprived neighbourhoods have higher rates of CHD, which represents important clinical knowledge. However, the association does not seem to be independent of individual- and family-level characteristics.


Model systems for understanding DNA base pairing.
The fact that nucleic acid bases recognize each other to form pairs is a canonical part of the dogma of biology. However, they do not recognize each other well enough in water to account for the selectivity and efficiency that is needed in the transmission of biological information through a cell. Thus proteins assist in this recognition in multiple ways, and recent data suggest that these mechanisms of recognition can vary widely with context. To probe how the chemical differences of the four nucleobases are defined in various biological contexts, chemists and biochemists have developed modified versions that differ in their polarity, shape, size, and functional groups. This brief review covers recent advances in this field of research.


ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages.
Acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies free cholesterol and stores cholesteryl esters in lipid droplets. Macrophage ACAT1 deficiency results in increased atherosclerotic lesion area in hyperlipidemic mice via disrupted cholesterol efflux, increased lipoprotein uptake, accumulation of intracellular vesicles, and accelerated apoptosis. The objective of this study was to determine whether lipid synthesis is affected by ACAT1. The synthesis, esterification, and efflux of new cholesterol were measured in peritoneal macrophages from ACAT1(-/-) mice. Cholesterol synthesis was increased by 134% (p=0.001) in ACAT1(-/-) macrophages compared to wildtype macrophages. Increased synthesis resulted in a proportional increase in the efflux of newly synthesized cholesterol. Although the esterification of new cholesterol was reduced by 93% (p<0.001) in ACAT1(-/-) macrophages, trace amounts of newly synthesized cholesteryl esters were detectable. Furthermore, the expression of SREBP1a mRNA was increased 6-fold in ACAT1(-/-) macrophages compared to wildtype macrophages, suggesting an up-regulation of cholesterol and fatty acid synthesis in ACAT1(-/-) macrophages. Increased cholesterol synthesis and up-regulation of SREBP in ACAT1(-/-) macrophages suggests that ACAT1 affects the regulation of lipid metabolism in macrophages. This change in cholesterol homeostasis may contribute to the atherogenic potential of ACAT1(-/-) macrophages.


[Dual roles and mechanism of microglia in ischemic stroke].
Stroke is the second most common cause of death after cancer worldwide and a major cause of acquired disability in adults. Overwhelming majority of strokes are caused by cerebral ischemia and are classified as ischemic stroke. Microglia are the resident immune cells and play dual roles in response to ischemia injury in the central nervous system (CNS). On the one hand, microglia may contribute to tissue function recovery process by promoting inflammation resolution, cellular debris clearance, nerve regeneration and synapse remodeling. On the other hand, excessive activation of microglia aggravates nerve damage after ischemic injury. Here, we briefly describe the mechanism of microglia activation after stroke, and comprehensively review the dual role of microglia in neurodegeneration and regeneration after stroke. In-depth exploration of the cytotoxic and protective mechanisms of microglia will provide new targets and new strategies for stroke treatment.


Controlling and measuring the equilibration of dynamic combinatorial libraries of imines.
Imine formation is one of the most powerful methods for the construction of azamacrocycles, especially when combined with Dynamic Combinatorial Chemistry. Careful NaBH 4 reduction of the imine libraries opens the possibility of determination of their composition via HPLC analysis of the resulting amine mixture. Templates, reagent concentrations, as well as reaction conditions influence the library composition.


Cholinergic innervation of the zebrafish olfactory bulb.
A number of fish species receive forebrain cholinergic input but two recent reports failed to find evidence of cholinergic cell bodies or fibers in the olfactory bulbs (OBs) of zebrafish. In the current study we sought to confirm these findings by examining the OBs of adult zebrafish for choline acetyltransferase (ChAT) immunoreactivity. We observed a diffuse network of varicose ChAT-positive fibers associated with the nervus terminalis ganglion innervating the mitral cell/glomerular layer (MC/GL). The highest density of these fibers occurred in the anterior region of the bulb. The cellular targets of this cholinergic input were identified by exposing isolated OBs to acetylcholine receptor (AChR) agonists in the presence of agmatine (AGB), a cationic probe that permeates some active ion channels. Nicotine (50 microM) significantly increased the activity-dependent labeling of mitral cells and juxtaglomerular cells but not of tyrosine hydroxlase-positive dopaminergic neurons (TH(+) cells) compared to control preparations. The nAChR antagonist mecamylamine, an alpha7-nAChR subunit-specific antagonist, calcium-free artificial cerebrospinal fluid, or a cocktail of ionotropic glutamate receptor (iGluR) antagonists each blocked nicotine-stimulated labeling, suggesting that AGB does not enter the labeled neurons through activated nAChRs but rather through activated iGluRs following ACh-stimulated glutamate release. Deafferentation of OBs did not eliminate nicotine-stimulated labeling, suggesting that cholinergic input is primarily acting on bulbar neurons. These findings confirm the presence of a functioning cholinergic system in the zebrafish OB.


Conformational change of hydroxyapatite/gelatin nanocomposite by glutaraldehyde.
The hydroxyapatite (HAp)/gelatin (GEL) nanocomposite was prepared through the coprecipitation and then cross-linked by using glutaraldehyde (GA). From FT-IR measurement the spectral features for amide bands and phosphate bands were severely modified by the cross-linkage and the organic content increased with the degree of cross-linkage. From Transmission Electron Microscopy (TEM) and electron diffraction analyses we could confirm the preferentially directional growth of needle-like HAp particles, which were embedded in GEL by the mineralization. Also we could observe worm-like stria patterns of contrast, which were revealed by the mineralization on the individual GEL fibrils. Moiré images were observed in a highly cross-linked HAp/GEL nanocomposite sample and we think the cross-linkage induced the assembly of unordered individual fibrils along the preferential direction.


Inadequate documentation of urinary tract infection symptoms in the medical chart.
We evaluated symptom documentation for 312 inpatients with bacteriuria by comparing information found in the chart with that obtained prospectively from the medical and nursing team caring for the patient. There was only moderate agreement (κ = 0.55), and only 77% of symptomatic patients had any symptom documented in the chart.


Need for Routine Preoperative Insertion of Indwelling Urinary Catheter Prior to Endovascular Repair of Abdominal Aortic Aneurysm.
Evaluate outcomes following urinary catheter (UC) versus no urinary catheter (NUC) insertion in elective endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). Retrospective record review of all elective EVAR at a university affiliated medical center over a 5-year period. Statistical analysis included Chi Sq, Independent Student t Test. Six surgeons performed 272 elective EVAR. Three surgeons preferred selective insertion of indwelling UC, such that 86 (32%) EVAR were completed without indwelling urinary catheters (NUC). Differences between NUC versus UC included; male: (86% vs. 70%; P = 0.004), CAD: (45% vs. 33%; p = 0.046), conscious sedation: (36% vs. 8%; P < 0.001), bilateral percutaneous EVAR (PEVAR): (100% vs. 90%; P = 0.01), within ProglideTM IFU guidelines (87% vs 75%; P = .05), major adverse operative event (MAOE): (3.5% vs. 10%; P = 0.05) and mean operative time (185 ± 73 vs. 140 ± 37; P < 0.001). Intra-operative catheterization was never required among NUC. Postoperative adverse urinary events (AUE) were more common among UC (11.4% vs. 8.1%; P = 0.41); with longer times to straight catheterization/reinsertion (1575 ± 987 vs, 522 ± 269 min; P = 0.015) and lower likelihood of eligibility for same day discharge (SDD); (41% vs. 59%; P = 0.008). Ineligibility for SDD was due to AUE in 18% of UC patients. Selective preoperative UC insertion should be considered for EVAR, with particular consideration to no preoperative catheterization in men meeting Proglide IFU. Adverse urinary events occurred less frequently among NUC and were identified/ treated earlier. Moreover, AUEs were the most common reason for potential SDD ineligibility among UC patients. Selective policies may facilitate SDD.


Retraction Note: Protective role of silymarin in a mouse model of renal Ischemia-Reperfusion injury.
This article [1] is retracted at request of the Editor. After publication of this article [1] concerns were raised regarding aspects of the methodology, including the choice of stains being inappropriate or inadequate to answer the research question. A discrepancy was also noted between the number of groups described in the methods and the number of groups presented in some of the figures. Furthermore the western blot images did not entirely correspond with the information reported in the results. For these reasons the conclusions of the study cannot be considered to be supported by the data. All authors agree to this retraction.


The virtual slice setup.
In an effort to design a simulation environment that is more similar to that of neurophysiology, we introduce a virtual slice setup in the NEURON simulator. The virtual slice setup runs continuously and permits parameter changes, including changes to synaptic weights and time course and to intrinsic cell properties. The virtual slice setup permits shocks to be applied at chosen locations and activity to be sampled intra- or extracellularly from chosen locations. By default, a summed population display is shown during a run to indicate the level of activity and no states are saved. Simulations can run for hours of model time, therefore it is not practical to save all of the state variables. These, in any case, are primarily of interest at discrete times when experiments are being run: the simulation can be stopped momentarily at such times to save activity patterns. The virtual slice setup maintains an automated notebook showing shocks and parameter changes as well as user comments. We demonstrate how interaction with a continuously running simulation encourages experimental prototyping and can suggest additional dynamical features such as ligand wash-in and wash-out-alternatives to typical instantaneous parameter change. The virtual slice setup currently uses event-driven cells and runs at approximately 2 min/h on a laptop.


Congenital heart defect and mental retardation in a patient with a 13q33.1-34 deletion.
13q deletion syndrome is a rare genetic disorder caused by deletions of the long arm of chromosome 13. Patients with 13q deletion display a variety of phenotypic features. We describe a one-year-old female patient with congenital heart defects (CHD), facial anomalies, development and mental retardation. We identified a 12.75Mb deletion in chromosome region 13q33.1-34 with high resolution SNP Array (Human660W-Quad, Illumina, USA). This chromosome region contains about 55 genes, including EFNB2, ERCC5, VGCNL1, F7, and F10. Comparing our findings with previously reported 13q deletion patients with congenital heart defects, we propose that the 13q33.1-34 deletion region might contain key gene(s) associated with cardiac development. Our study also identified a subclinical deficiency of Factors VII and X in our patient with Group 3 of 13q deletion syndrome.


In-hospital cardiopulmonary resuscitation: organization, management and training in hospitals of different levels of care.
: During recent years in-hospital cardiopulmonary resuscitation (CPR) management has received much attention. This can be attributed to the Utstein model for in-hospital CPR developed in 1997. The present status of in-hospital resuscitation management in Finnish hospitals is not known. Therefore, a study was designed to describe the organization of training and clinical management of CPR in Finnish hospitals of different levels of care. : In the summer of 2000, we performed a cross-sectional mail survey throughout Finland, including all district, central and university hospitals. The questionnaire outlined in detail in-hospital resuscitation management and training. For analysis the hospitals were divided into primary, secondary and tertiary groups, depending on levels of care. : Most hospitals (72%) reported having a physician or a nurse in charge of resuscitation management and training. Training in advanced life support was more common among nurses (80%) than among physicians (53%). Surprisingly, a majority of respondents (75%) reported that they felt training in CPR was insufficient. On the general wards and on wards treating cardiac patients, defibrillation was in most cases performed by a physician (91% and 51%, respectively), and less often by a nurse (16% and 31%, respectively). In the secondary and tertiary hospitals cardiac arrest was managed by a cardiac arrest team (53% and 62%, respectively) and in the primary hospitals by the ward physician (56%), anesthesiologist or emergency physician on call (44%). Most hospitals used do-not-resuscitate orders (83%) but only 33% of the hospitals had a unified style of notation. Systematic data collection was practised in 55% of hospitals, predominantly by using a model of their own. Only a few hospitals (11%) used the in-hospital Utstein model. : Our study showed that more attention needs to be paid to CPR management in Finnish hospitals. At present, 25% of hospitals do not have an appointed physician or nurse in charge of organizing CPR management. The study also revealed a lack of regular organized training in resuscitation for physicians. Fifty-five per cent of hospitals practise systematic data collection, but only 11% according to the Utstein template; and without which further quality assurance is difficult.


Acute Care Surgery Service Is Essential During a Nonsurgical Catastrophic Event, the COVID-19 Pandemic.
The role of an acute care surgery (ACS) service during the COVID-19 pandemic is not well established. A retrospective review of the ACS service performance in an urban tertiary academic medical center. The study was performed between January and May 2020. The demographics, clinical characteristics, and outcomes of patients treated by the ACS service 2 months prior to the COVID surge (pre-COVID group) and during the first 2 months of the COVID-19 pandemic (surge group) were compared. Trauma and emergency general surgery volumes decreased during the surge by 38% and 57%, respectively; but there was a 64% increase in critically ill patients. The proportion of patients in the Department of Surgery treated by the ACS service increased from 40% pre-COVID to 67% during the surge. The ACS service performed 32% and 57% of all surgical cases in the Department of Surgery during the pre-COVID and surge periods, respectively. The ACS service managed 23% of all critically ill patients in the institution during the surge. Critically ill patients with and without confirmed COVID-19 infection treated by ACS and non-ACS intensive care units during the surge did not differ in demographics, indicators of clinical severity, or hospital mortality:13.4% vs. 13.5% (P = .99) for all critically ill patients; and 13.9% vs. 27.4% (P = .12) for COVID-19 critically ill patients. Acute care surgery is an "essential" service during the COVID-19 pandemic, capable of managing critically ill nonsurgical patients while maintaining the provision of trauma and emergent surgical services. III. Therapeutic.


FTY720 attenuates acute colitis via colonic T cells reduction and inhibition of M1 macrophages polarization independent of CCR2-mediated monocytes input.
Ulcerative colitis (UC) is a complex multifactorial disease, of which the exact etiology is not fully understood. The inappropriate aggressive inflammatory response is closely related to the disease progression of UC. FTY720 is a sphingosine-1-phosphate receptor agonist and acts as a key immunomodulator in inflammation. This study aims to investigate the protective influence of FTY720 on inflammation in the DSS-induced colitis model. In the present study, the C57BL/6 mice and the CCR2-/- mice were exposed to 5% Dextran Sodium Sulfate (DSS) drinking water for 6 days followed by an injection of FTY720 (1 mg/kg/d) or vehicle (PBS) 6 times starting on the next day. The body weight, stool consistency, and occult blood were assessed daily. The inflammatory cytokines level in colon tissues and serum were assessed. Leukocyte subsets of bone marrow (BM), spleen, and colon were analyzed by flow cytometry. Our results demonstrated that FTY720 ameliorated the aberrant immune responses by trapping T cells and inhibiting the polarization of M1 macrophages in colitis mice. The effect of FTY720 on the increased number of colonic macrophages did not dependent on CCR2-mediated monocyte influx, despite most monocytes being reduced after DSS administration in the inflamed colon of CCR2-/- mice. Rather, depletion of CCR2 did not impact the protective influence of FTY720 on colonic injury in acute colitis. All these findings unravel a beneficial function of FTY720 in the inflammatory response to DSS-induced acute colitis, provided further insights into monocyte migration and might provide potential opportunities for UC therapeutic intervention.


Military Environmental Exposure Concerns, Posttraumatic Stress Disorder, and Somatic Symptoms: Their Interrelation Among Treatment-Seeking Veterans.
Research suggests military environmental exposure concerns are associated with negative health outcomes. This study investigated the relationship among exposure concerns, Posttraumatic Stress Disorder (PTSD), and somatic symptoms to enhance post-deployment health care programs for veterans. We analyzed intake health data from a heterogeneous sample of predominantly Operation Desert Storm/Shield and Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans (N = 247). Individual exposure concerns and somatic symptoms were associated with higher PTSD symptom severity. Regression modeling demonstrated total exposure concerns and PTSD symptom severity linked with total somatic symptom severity. Mediation modeling revealed PTSD symptom severity to partially explain the relation between exposure concerns and somatic symptoms. These findings illustrate the need for integrative treatment approaches incorporating physiological and exposure-related concerns associated with PTSD among veterans.


Extraction of proteins from Saccharomyces cerevisiae ribosomes under nondenaturing conditions.
The differential sensitivity of ribosomal proteins to removal by salts has been studied. Proteins were extracted from the large and small subunits of cytoplasmic ribosomes from Saccharomyces cerevisiae by washing the individual subunits with a series of solutions containing increasing concentrations of NH4Cl (0.74-3.56 M) for a defined time (20 min) at 0 degrees C. The molar ratio of magnesium to ammonium ions of 1:40 was maintained to protect the ribosomal subparticles from complete disassembly. Proteins extracted under each salt condition were analyzed for composition by two-dimensional polyacrylamide gel electrophoresis. The relative quantity of each protein was determined. Most proteins were not removed from the ribosomal particle completely by any one condition, but were preferentially enriched in a single fraction. Whereas most proteins could be solubilized, several proteins remained predominantly or exclusively with the final core particle. The kinetics of protein release from both subunits at a single NH4Cl concentration (0.74 M) were also studied. Release of protein was time dependent, i.e., longer extraction generally removed more of the same proteins. However, prolonged treatment (240 min) of subunits, even at the same salt concentration, resulted in removal of additional species of proteins in varying amounts. Among the ribosomal RNA species, only the 5 S RNA species was released from the ribosomal particles upon treatment.


[A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura].
Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.


New monolithic chromatographic supports for macromolecules immobilization: challenges and opportunities.
This mini-review reports on some recent advances in the field of immobilized protein employing both silica and polymer-based monoliths as supports, and their application in affinity chromatography and immobilized enzyme reactors (IMERs) developments. The major emphasis is put on some interesting challenges and opportunities related to the development of new monolithic affinity supports based on biofriendly sol-gel inorganic monoliths with entrapped proteins and on organic monolithic supports with improved hydrophilicity for IMERs development in proteomic studies. The ease of preparation of monoliths and the multitude of functionalization techniques, make monoliths interesting for an increasing number of biochemical and medical applications.


Iliac vein to pulmonary artery missile embolus: case report and review of the literature.
Intravascular foreign body emboli, although first reported in 1834, are rare sequelae of penetrating injuries. We report a case of missile embolus to the pulmonary artery after penetrating injury to the left iliac vein and artery. A review of the literature and discussion of appropriate management are presented.


Trends in dietary energy, fat, carbohydrate and protein intake in Chinese children and adolescents from 1991 to 2009.
Few studies have examined nutrition transition in children in China. Our aim, in the present study, was to examine temporal trends in dietary energy, fat, carbohydrate and protein intake in Chinese children aged 7-17 years. The analysis used individual level, consecutive 3 d dietary recall data from seven rounds of the China Health and Nutrition Surveys in 1991 (n 2714), 1993 (n 2542), 1997 (n 2516), 2000 (n 2142), 2004 (n 1341), 2006 (n 1072) and 2009 (n 996). Mixed-effect models were constructed to obtain adjusted means and to examine trends after adjusting for intra-class correlation within clusters and for covariates including age, sex, urban/rural residence and income. From 1991 to 2009, daily energy intake steadily declined from 9511·0 to 7658·2 kJ (P<0·0001). There was a steady decline in daily carbohydrate intake from 382·5 to 254·1 g (P<0·0001), and in the proportion of energy from carbohydrate from 66·7 to 56·8 % (P<0·0001). In contrast, daily fat intake steadily increased from 54·8 to 66·0 g (P<0·0001), as did the proportion of energy from fat from 21·5 to 30·0 % (P<0·0001). The proportion of children who consumed a diet with more than 30 % of energy from fat increased from 20·1 to 49·4 % (P<0·0001). The proportion of energy from protein increased from 11·8 to 13·1 % (P<0·0001), although daily protein intake dropped from 66·2 to 58·0 g (P<0·0001). Our data suggest that Chinese children have been undergoing a rapid nutrition transition to a high-fat diet.


Reproductive axis ageing and fertility in men.
Compared to women, increasing male age is not accompanied by such marked changes in reproductive function but changes certainly do happen. These include alterations to the hypothalamo-pituitary-testicular axis, with resultant implications for testosterone production and bioavailability as well as spermatogenesis. There is a decline in sexual function as men age, with a dramatic increase in the prevalence of erectile dysfunction after the age of 40, which is a marker for both clinically evident as well as covert coronary artery disease. Despite a quantitative decline in spermatogenesis and reduced fecundability, the male potential for fertility persists throughout adult life, however there are also increasingly recognised alterations in sperm quality and function with significant implications for offspring health. These changes are relevant to both natural and medically assisted conception.


Distant Metastasis in Pediatric and Adolescent Differentiated Thyroid Cancer: Clinical Outcomes and Risk Factor Analyses.
The specific characteristics of pediatric and adolescent differentiated thyroid cancer (DTC) is the more frequent occurrence of distant metastasis (DM) compared with adult DTC. To investigate the clinical outcomes of DM in this population and analyze risk factors related to DM. Medical records of 171 patients with DTC < 19 years old, who underwent initial surgery between 1979 and 2014 were retrospectively reviewed. Clinical responses to radioiodine (RAI) therapy evaluated by the American Thyroid Association (ATA) guidelines for adult DTC and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Risk factors related to distant-metastasis-free survival (DMFS). DM was observed in 29 patients, and all were lung metastases. The pattern of lung metastasis was classified into 3 categories: macronodular, micronodular, and no apparent nodule (detected only by RAI scintigraphy). Patients with excellent responses according to the ATA guideline criteria or complete remission of the RECIST criteria were most frequently observed in those with no apparent nodule. Significant factors related to DMFS were sex, clinical lymph node metastasis (LNM), extrathyroidal extension, and number of LNM. Subjects were divided into 3 groups according to the number of risk factors: low risk (no risk factors); intermediate risk (1 risk factor); and high risk (≥2 risk factors). Twenty-year DMFS rates in the low-, intermediate-, and high-risk groups were 99.0%, 71.7%, and 28.6%, respectively. To achieve the full efficacy of RAI therapy, early diagnosis of DM before apparent metastases appear is desirable. The selective approach would be preferable for pediatric and adolescent DTC.


Antibacterial Co(II) and Ni(II) Complexes of N-(2-Furanylmethylene)-2-Aminothiadiazole and Role of SO(4), NO(3), C(2)O(4) and CH(3)CO(2) anions on Biological Properties.
Co(II) and Ni(II) complexes with a Schiff base, N-(2-furanylmethylene)-2-aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The synthesized Schiff-bases act as tridentate ligands during the complexation reaction with Co(II) and Ni(II. metal ions. They possess the composition [M(L)(2)]X(n) (where M=Co(II) or Ni(II), L=, X=NO(3) (-), SO(4) (2-), C(2)O(4) (2-) or CH(3)CO(2) (-) and n=1 or 2) and show an octahedral geometry. In order to evaluate the effect of anions upon chelation, the Schiff-base and its complexes have been screened for antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.


Economic impacts of the mortality rate for suckling pigs in the United States.
To measure economic impacts attributable to the mortality rate for suckling pigs in the United States. Economic analysis that incorporated data from various sources. Suckling pigs on U.S. swine farms. Economic impacts associated with the mortality rate for suckling pigs during 1995 were estimated from supply-and-demand curves for pork and from an estimate of the elasticity of production for pigs entering the grower-finisher phase of production. A decrease in the mortality rate for suckling pigs would have caused an increase in pork production and a decrease in price and total value of production. Assuming no suckling pigs had died during 1995, consumer surplus would have increased by (mean +/- SE) 430 +/- 160 million dollars, whereas producer surplus would have decreased by 180 +/- 140 million dollars. The total gain to the US economy would have been 250 +/- 30 million dollars. Researchers who attempt to estimate the economic impact of mortality and morbidity rates of livestock should not ignore the influence of demand and the possibility of price adjustments. Consumers would stand to benefit from an increase in pork production associated with a reduction in the mortality rate for suckling pigs, whereas the swine industry would experience an economic loss. Individual producers need to compare the costs of measures intended to reduce the mortality rate for suckling pigs with the anticipated benefits.


Coombs-positive autoimmune hemolytic anemia in ulcerative colitis.
Coombs-positive autoimmune hemolytic anemia is a rare complication of ulcerative colitis, occurring in fewer than 1% of cases. We have found eight patients with autoimmune hemolytic anemia in a series of 1150 hospitalized patients with ulcerative colitis (0.7%). There was a marked preponderance of female patients F:M = 7:1, in accord with previous reports. The hemolytic anemia appeared at a mean of 10 years after the onset of colitis, apparently independent of the age of the patient. Although seven of the eight patients had active colitis at the time of diagnosis of anemia, there was no consistent relationship to the extent of the bowel disease. Seven of the eight patients survived. One patient showed a partial response to steroid therapy, two responded to splenectomy, but four required both colectomy and splenectomy. Steroids should be the first line of therapy followed by splenectomy, if necessary. For those patients who have severe colitis, which in itself would merit surgery, a total proctocolectomy combined with splenectomy seems advisable.


Comparing perceptions of long-acting reversible contraception among women during periods of incarceration and women attending a local clinic: An exploratory study.
The objective of this study was to understand perceptions of long-acting reversible contraception (LARC) among incarcerated women. We compared survey responses specific to IUDs and implants between a convenience sample of incarcerated women to a sample of women attending a local ob/gyn clinic. We conducted a cross-sectional survey among two groups: (1) incarcerated women receiving medical care at the state correctional facility, and (2) women receiving care at an ob/gyn clinic in the same community. The anonymous survey included questions about demographic variables, current and past contraceptive use, and perception of IUDs and implants. Almost half of the total sample stated that they might consider an IUD or implant for contraception. Incarcerated women tended to be less likely to give an affirmative answer to current or future use of an IUD or implant (29% vs 39%, p = 0.19). Concerns about pain and side effects were similar between the groups, but more incarcerated women cited concerns about device removal (72% vs 57%, p = 0.02) and the level of training of the provider inserting the device (68% vs 53%, p = 0.02). Incarcerated women interested in using the IUD or implant were more comfortable with device placement in the community than in the correctional setting (42% to 30%, p < 0.001). Incarcerated women have concerns about LARC that may be specific to their experience of incarceration. Providers working with incarcerated women should consider these when counseling patients on contraceptive choices. Options for post-release follow-up care and device removal should be included in this discussion. Incarcerated women should receive comprehensive reproductive health care, including contraceptive services if desired. However, incarceration itself may introduce fundamental concerns regarding contraception and these concerns need to be better understood to balance the provision of services with the potential for reproductive coercion.


Inflammatory pathways in spondyloarthritis.
Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional evidence from human and animal studies support a role of these pathways in the disease. TNF has a key role in SpA as blockade significantly reduces inflammation and destruction, however the treatment does not halt new bone formation. New insights into the TNF pathway were recently obtained from an animal model specifically overexpressing the transmembrane form of TNF. This model leads to axial and peripheral new bone formation which is not seen in soluble TNF overexpression models, indicating different pathogenic roles of soluble and transmembrane TNF in arthritis development. Besides TNF, the IL-23/IL-17 axis is emerging as an important inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17 blockade has been shown to be efficacious for AS patients in a phase II trial. In this review, we focus on the cytokine pathways that have recently been genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review the current genetic, experimental and human in vivo data available and discuss how these different pathways are involved in the pathophysiology of SpA. Additionally, we discuss how these pathways relate to the pathogenic new bone formation in SpA.


Effectiveness of drug-eluting stent implantation for patients with unprotected left main coronary artery stenosis.
This study was aimed to evaluate outcomes of patients with unprotected left main coronary artery (LMCA) stenosis who were treated with drug-eluting stents. Sixty-three consecutive patients with unprotected LMCA stenosis were treated with sirolimus-eluting stents in 52 (83%) patients and paclitaxel-eluting stents in 11 (17%) patients, in whom percutaneous intervention was considered the sole alternative because of high surgical risk and/or patient preference. Urgent percutaneous coronary intervention within 24 hours after angiography was performed in 6 (10%) patients. The patients were predominantly at high surgical risk with 35 (56%) having EuroSCORE >6 and 39 (62%) having Parsonnet score >15. Involvement of the distal LMCA was observed in 46 (73%) patients. Procedural success was achieved in all patients. Intravascular ultrasound was used in 51 (81%) patients. Single-stenting strategy was adopted in 36 (78%) patients with bifurcation stenosis. There were no death, Q-wave myocardial infarction, stent thrombosis, or urgent repeat revascularization events during hospitalization. Over a mean follow-up of 11.7 +/- 7.7 months, 18 (29%) patients experienced major adverse cardiac events, including 3 (5%) deaths, 7 (11%) myocardial infarctions, and 10 (16%) target lesion revascularizations. Stent thrombosis developed in 1 (0.6%) patient at 35 days after the procedure. Bifurcation involvement was an independent predictor of major adverse cardiac events by multivariate analysis (hazard ratio 12.90, 95% confidence interval 1.36 to 122.45, p = 0.0259). In conclusion, drug-eluting stent placement for unprotected LMCA stenosis may be a feasible therapeutic alternative in patients at high surgical risk. However, bifurcation stenosis remains a significant predictor of unfavorable clinical outcome.


Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma.
The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.


Steroids and related products. LIV. The synthesis of 11-oxa steroids. VI. The synthesis of 11-oxatestosterone.
The synthesis of 11-oxatestosterone from 11-oxa-5 alpha-androstane-3,17-dione, which is available from hecogenin, is described. The product shows, in comparison with the natural hormone, diminished androgenic and anabolic activities.


Bioclimatic dataset of Metropolitan France under current conditions derived from the WorldClim model.
Several studies have shown that adequate bioclimatic information is of major importance for mapping ecological niches or for modelling the distribution ranges of species and communities, particularly from a climate change perspective [1,2]. However, in France, there are few data sources that provide consistent information, available data being produced at low spatial resolution and based on classification systems that are not suitable for mapping French ecological systems. This paper presents bioclimatic maps produced on Metropolitan France and based on the Worldwide Bioclimatic Classification System, which are called Global Bioclimatics [3]. This data paper documents a set of variables that includes 23 bioclimatic maps generated according to the Worldwide Bioclimatic Classification System. These maps describe current bioclimatic conditions in Metropolitan France at a resolution of 30 arc-seconds. Climatic parameters and bioclimatic indices usually used for the analysis or modelling of species and communities' distribution, and bioclimatic typological units, were calculated using the temperature and precipitation data derived from the WorldClim 2 model. These maps can be used in GIS or models by researchers for mapping ecological conditions, but can also provide natural resource managers with analytical tools to assess Nature conservation policies.


Extracellular vesicles from hair follicle-derived mesenchymal stromal cells: isolation, characterization and therapeutic potential for chronic wound healing.
Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have demonstrated to elicit immunomodulatory and pro-regenerative properties that are beneficial for the treatment of chronic wounds. Thanks to different mediators, MSC-EVs have shown to play an important role in the proliferation, migration and cell survival of different skin cell populations. However, there is still a big bid to achieve the most effective, suitable and available source of MSC-EVs. We isolated, characterized and compared medium-large EVs (m-lEVs) and small EVs (sEVs) obtained from hair follicle-derived MSCs (HF-MSCs) against the gold standard in regenerative medicine, EVs isolated from adipose tissue-derived MSCs (AT-MSCs). We demonstrated that HF-EVs, as well as AT-EVs, expressed typical MSC-EVs markers (CD9, CD44, CD63, CD81 and CD105) among other different functional markers. We showed that both cell types were able to increase human dermal fibroblasts (HDFs) proliferation and migration. Moreover, both MSC-EVs were able to increase angiogenesis in human umbilical vein endothelial cells (HUVECs) and protect HDFs exposed to a hyperglycemic environment from oxidative stress and cytotoxicity. Taken together, HF-EVs demonstrated to exhibit comparable potential to that of AT-EVs as promising candidates in the treatment of chronic wounds.


Thyroid hormone effects on protein and RNA metabolism in the rat anterior pituitary.
Thyroidectomy reduced the incorporation of [3H]amino acids into total rat pituitary proteins as well as into electrophoretic fractions corresponding to growth hormone (GH) and prolactin. A single injection of thyroxine (200 microgram/kg) reversed the effects of thyroidectomy on the GH (12 h) and prolactin (36 h) fractions. Evidence for a general increase in the rate of pituitary protein synthesis following this treatment was less conclusive, but two injections of the hormone had a definite stimulatory effect. [3H]Uridine uptake by the pituitary and its incorporation into RNA were elevated for 2 weeks after thyroidectomy. Thyroxine failed to suppress these changes for at least 36 h after injection. Actinomycin C (400 microgram/kg) inhibited pituitary RNA synthesis and blocked the stimulatory effect of thyroxine on amino acid incorporation into the GH fraction. These results indicate that thyroid hormones: (1) promote pituitary protein synthesis, probably as a consequence of their effects on somatotrophs and lactotrophs; (2) exert a stimulatory effect on GH synthesis by affecting transcription.


Decreased fibrinolytic activity in porcine-to-primate cardiac xenotransplantation.
One major barrier to successful xenotransplantation is acute vascular rejection, a process pathologically characterized by microvascular thrombosis and diffuse fibrin deposition in transplant blood vessels. This pathologic picture may result from a disturbance in the coagulant or fibrinolytic pathways that regulate normal vascular patency. This study evaluated the regulation of fibrinolytic activity defined by tissue plasminogen activator and plasminogen activator inhibitor-1 as it may exist in the setting of acute vascular rejection. Serial biopsies from cardiac xenotransplants evaluated by immunofluorescence microscopy demonstrated progressive decreases in tissue plasminogen activator and increases in plasminogen activator inhibitor-1. In vitro studies measuring fibrinolytic activity of cell culture medium from porcine aortic endothelial cells stimulated with human serum or autologous porcine serum revealed that human serum triggered as much as 93% increase in antifibrinolytic activity. These findings demonstrate that porcine vascular endothelial cells change toward an antifibrinolytic state following stimulation with human xenoreactive antibodies and complement. The shift is at least partly explained by an increased ratio of plasminogen activator inhibitor-1 to tissue plasminogen activator, and is at least in part mediated by the activation of complement. This increased antifibrinolytic activity may contribute to the thrombotic diathesis seen in acute vascular rejection in pig-to-primate xenografts.


DGAT1 protects tumor from lipotoxicity, emerging as a promising metabolic target for cancer therapy.
We recently demonstrated that glioblastoma, the most lethal brain cancer, upregulates diacylglycerol O-acyltransferase 1 (DGAT1) to store excess fatty acids into triglycerides to prevent lipotoxicity and promote tumor growth. Targeting DGAT1 resulted in marked tumor cell death by triggering extensive oxidative stress, indicating that DGAT1 could be a promising target for cancer therapy.


Transverse evolution of a plasma channel in air induced by a femtosecond laser.
We investigate the evolution of filamentation in air by using a longitudinal diffraction method and a plasma fluorescence imaging technique. The diameter of a single filament in which the intensity is clamped increases as the energy of the pump light pulse increases, until multiple filaments appear.


Glutaraldehyde inactivation of exotic animal viruses in swine heart tissue.
Glutaraldehyde, 0.2%, in a 1:100 (wt/vol) ratio, inactivated four animal viruses (foot-and-mouth disease, swine vesicular disease, African swine fever, hog cholera) in swine heart tissues during 11-day exposures at 22 to 26 degrees C.


Mortality from respiratory disease at follow-up of patients with asthma.
Over a 20-year period 765 men and 1127 women with asthma were followed up; 272 men and 282 women died compared with expected deaths of 165 men and 185 women. As anticipated there was an appreciable number of deaths attributed to asthma but an even higher absolute excess of deaths attributed to bronchitis when compared with the expected numbers. The relative excess from asthma and bronchitis was highest in the younger subjects. Mortality from all other causes was lower than expected.


Autophagy Regulation of Bacterial Pathogen Invasion.
Autophagy pathway is highly conserved in all eukaryotic species and responsible for targeting of cytosol components, such as protein aggregates, damaged or unnecessary organelles, and intracellular bacterial pathogens for lysosome-dependent degradation. Besides severing as a catabolic process, autophagy pathway furthermore has been discovered to function pivotally in both innate and adaptive immune responses. At present, it has been well demonstrated that certain types of bacteria could be targeted by autophagy upon their invasion. However, several bacterial pathogens have developed strategies to evade this degradation and clearance. Here, we review the role and mechanism of autophagy in the regulation of bacteria invasion, which may facilitate the designing of clinical drugs for efficient and safe cure of infection diseases caused by toxic bacteria.


Recognition by a murine monoclonal antibody of a unique epitope specific for the human alloantigen HLA-B8.
A cytotoxic murine monoclonal antibody recognizing a specific HLA alloantigen was produced from the spleen cells of a BALB/c immunized with partially purified class I glycoproteins from an HLA-A1,B8 homozygous B-lymphoblastoid cell line. The antibody, designated P8.1, was tested against cells from 521 unrelated donors. It reacted with each of the 83 donors known to be HLA-B8 positive and with no HLA-B8 negative donors (sensitivity, 100%; specificity, 100%). Immunoprecipitation with antibody P8.1 and polyacrylamide gel electrophoresis confirmed that the antigen recognized was a class I structure. Although most murine monoclonal anti-HLA antibodies previously described have recognized "public" or supertypic specificities, the identification of a monoclonal antibody specific for a "private" HLA alloantigen indicates first that the BALB/c mouse has the appropriate immune response repertoire for recognizing certain HLA allospecificities and second that HLA-B8 can be defined by a single unique epitope.


The Effect of Intratumoral Interrelation among FOXP3+ Regulatory T Cells on Treatment Response and Survival in Triple-Negative Breast Cancer.
Triple-negative breast cancer (TNBC) is characterized by an active immune response. We evaluated intratumoral interrelation between FOXP3+ tumor-infiltrating lymphocytes and other cytokines in TNBC. Network analysis refined cytokines significantly correlate with FOPX3 in TNBC. Information on the treatment response and prognosis of patients, and survival data from the TGCA and METABRIC databases were analyzed according to refined cytokines. Interleukin (IL)-33 was significantly expressed by TNBC cell lines compared to luminal cell lines (log2 fold change: 5.31, p < 0.001) and IL-33 and TGFB2 showed a strong correlation with FOXP3 in the TNBC cell line. Immunohistochemistry demonstrated that the IL-33 high group was a significant predictor of complete response of neoadjuvant chemotherapy (odds ratio (OR) 4.12, p < 0.05) and favorable survival compared to the IL-33 low group (OR 6.48, p < 0.05) in TNBC. Survival data from TGCA and METABRIC revealed that FOXP3 was a significantly favorable marker in the IL-33 high group compared to the low IL-33 low group (hazard ratio (HR) 2.1, p = 0.02), and the IL-33 high/TGFB2 high subgroup showed significant favorable prognosis in the FOXP3 high group compared to the FOPX3 low group in TNBC (HR 3.5, p = 0.01). IL-33 and TGFB2 were key cytokines of intratumoral interrelation among FOXP3 in TNBC.


Vitamin B-12: placebo or neglected therapeutic tool?
Patients with normal serum vitamin B-12 levels were given injections of hydroxocobalamin (vitamin B-12b) interspersed with injections of sterile water. Those who felt better with B-12b had additional injections to establish the amount of B-12b that gave the maximum feeling of well-being. Serum vitamin B-12 tests were performed to record the level at which the patients felt best. On the same day they took a Multiphasic Personality Inventory (MMPI), an objective computerized psychological test. Hydroxocobalamin injections were then discontinued for 5 to 7 days. The patients took another serum vitamin B-12 test and another MMPI. With the higher vitamin B-12 levels, the MMPI patterns were at or closer to normal. With lower serum vitamin B-12 levels, MMPI patterns showed much more emotional distress. The author suspects that vitamin B-12 dependency disorders are common and are neglected by the medical profession.


Distribution, sources and risk assessment of polychlorinated biphenyls in soils from the Midway Atoll, North Pacific Ocean.
Concentrations of 28 polychlorinated biphenyls (PCBs) were assessed in soils from the Midway Atoll in the central North Pacific Ocean. The analytical procedure involved the application of accelerated solvent extraction (ASE) and gas chromatography coupled with ion trap mass spectrometric detection (GC/ITMS) for identification and quantification. Among the 28 PCB congeners studied, 26 of them, except CB195 and CB209, were detected in the analyzed samples at different frequencies. The total concentrations of 28 indicator PCBs (ΣPCBs) ranged from 2.6 to 148.8 ng g⁻¹ with an average value of 50.7 ng g⁻¹ and median of 39.5 ng g⁻¹. Sources and congeners' pattern of PCB were investigated in the soil of Midway Atoll. The principal component analysis indicated that the compositions of PCBs in most of the soil samples were similar. The total concentrations of PCBs were used to assess the cancer risk probabilities in humans via ingestion, dermal contact and inhalation of soil particles. Very low cancer risk was found in all soil samples caused by ΣPCBs.


Identification of a second member of the ponticulin gene family and its differential expression pattern.
We have identified a homologue (ponB) of the ponticulin gene (ponA), an F-actin binding protein, in the expressed sequence tag library generated to mRNA isolated from fusion-competent cells of Dictyostelium discoideum. PonB is predicted to have many of the same characteristics as ponticulin. Both proteins are predicted to possess a cleaved signal peptide, a glycosyl anchor, an amphipathic beta-strand structure and six conserved cysteines. Because of the sequence similarity and predicted conserved structures, this gene constitutes the second member of a ponticulin gene family. Unlike ponticulin, ponB is not expressed in axenically grown cells or during the asexual reproductive phase of D. discoideum. PonB is expressed by cells grown on bacterial lawns and by cells induced to be fusion-competent, i.e., gametes. The expression of ponB correlates with the appearance of a new F-actin binding activity in cell lysates of bacterially grown ponA(-) cells. By immunofluorescence microscopy, ponB appears to be localized to vesicles and to the plasma membrane of bacterially grown cells. Because ponticulin is the major high-affinity link between the plasma membrane and the cytoskeleton, the ponticulin gene family is likely to be part of the redundant system of proteins involved in connecting the cytoskeleton to the plasma membrane.


The protocol-guided rapid evaluation of veterans experiencing new transient neurological symptoms (PREVENT) quality improvement program: rationale and methods.
Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles. This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability. PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines. clinicaltrials.gov: NCT02769338 [May 11, 2016].


Bridging the Gap Between Radiology and Primary Care: Expansion and Sustainability of a Medical Imaging Call Center Model.
The Medical Imaging Call Centre (MICC) was an initiative carried out by a hospital-based academic imaging department with the aim to provide navigational services and radiologist consultations to community-based primary care physicians (PCPs). The strategies used to expand and sustain the initiative over a 3.5-year period after an initial pilot are described. The strategy to evolve the MICC had internal and external components. Internally, processes were refined to ensure satisfaction of stakeholders. Externally, a robust engagement strategy focused on recruiting and engaging callers was implemented. Metrics including call volumes, unique callers, and call type were monitored to track utilization and further inform the engagement strategy. A reduction in avoidable use of the emergency department (ED) was determined by tracking pre- and post radiologist consultation decisions reported by callers. During the evaluation period, 2,297 calls were made. There was a 39% increase in the average number of monthly calls in the last 6-month period (61) compared with the first 6 months (44). Call types that involved PCP-to-radiologist communication for patient management consultation also increased over time. A 98% ED avoidance rate (215 of 220) was reported for calls in which PCPs initially indicated that they would be sending their patients to the ED for urgent imaging if the MICC were unavailable. The MICC was successful in connecting community-based PCPs with hospital-based subspecialized radiologists. Results indicate that an active engagement strategy is necessary and can lead to changes in patient management that will decrease the burden on other specialists.


Loss of the PTCH1 gene locus in cardiac fibroma.
Cardiac fibroma (CF) is a rare benign tumor that is poorly characterized genetically. CF is more commonly encountered in patients with Gorlin syndrome (3%) than the general population. Mutations of the tumor suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. Conventional cytogenetic analysis was performed on a peripheral blood and a CF sample from a 2-week-old male. In addition, fluorescence in situ hybridization (FISH) studies were performed to assess the copy number of the PTCH1 gene locus (9q22.3) on metaphase and interphase cells from these same specimens using yeast artificial protein (YAC) probe 891G1 and on representative paraffin-embedded tissue sections of two additional CFs (one arising in a 2-month-old female and the other in a 13-week-old male). None of the patients had Gorlin syndrome. Karyotypically, the following abnormal chromosomal complement was detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF and in the CF arising in the 13-week-old male. Heterozygous loss of this locus was identified in the remaining CF from the 2-month-old female. A mutational mechanism other than deletion may be responsible for PTCH1 inactivation on the other locus in this latter patient. Conventional cytogenetic and FISH studies of the peripheral blood sample from the 2-week-old male were normal. These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or sporadic CFs.


Effect of exercise-meal timing on energy intake, appetite and food reward in adolescents with obesity: The TIMEX study.
The present study manipulated the delay between exercise and test meal to investigate its effect on energy intake, appetite sensations and food reward in adolescents with obesity. Fifteen adolescents with obesity randomly completed 3 experimental sessions: i) rest without exercise (CON); ii) 30 min of exercise 180 min before lunch (EX-180); iii) 30 min of exercise 60 min before lunch (EX-60). Ad libitum energy intake was assessed at lunch and dinner, and food reward (LFPQ) assessed before and after lunch. Appetite sensations were assessed at regular intervals. Absolute energy intake was not different between conditions despite a 14.4% lower intake in EX-60 relative to CON. Lunch relative energy intake (REI: energy intake - exercise-induced energy expenditure) was higher in CON compared with EX-60 (p < 0.001). Lunch fat intake was lower in EX-60 compared with CON (p = 0.01) and EX-180(p = 0.02). Pre-lunch hunger in CON was lower than EX-180 (p = 0.02). Pre-lunch prospective food consumption and desire to eat were lower in CON compared with both exercise conditions (p = 0.001). A significant condition effect was found for explicit liking for high-fat relative to low-fat foods before lunch (p = 0.03) with EX-60 being significantly lower than EX-180 (p = 0.001). The nutritional and food reward adaptations to exercise might be dependent on the timing of exercise, which is of importance to optimize its effect on energy balance in adolescents with obesity. CLINICAL TRIAL REFERENCE: NCT03807609.


Primary decompressive craniectomy in poor-grade aneurysmal subarachnoid hemorrhage: long-term outcome in a single-center study and systematic review of literature.
Primary decompressive craniectomy (PDC) in patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) in order to decrease elevated intracranial pressure (ICP) is controversially discussed. The aim of this study was to analyze the effect of PDC on long-term clinical outcome in these patients in a single-center cohort and to perform a systematic review of literature. Eighty-seven consecutive poor-grade SAH patients (World Federation of Neurosurgical Societies (WFNS) grades IV and V) were analyzed between October 2012 and August 2017 at the author's institution. PDC was performed due to clinical signs of herniation or brain swelling according to the treating surgeon. Outcome was analyzed according to the modified Rankin Scale (mRS). Literature was systematically reviewed up to August 2019, and data of poor-grade aSAH patients who underwent PDC was extracted for statistical analyses. Of 87 patients with poor-grade aSAH in the single-center cohort, 38 underwent PDC and 49 did not. Favorable outcome at 2 years post-hemorrhage did not differ significantly between the two groups (26% versus 20%). Systematic literature review revealed 9 studies: Overall, a favorable outcome could be achieved in nearly half of the patients (49%), with an overall mortality of 24% (median follow-up 11 months). Despite a worse clinical status at presentation (significantly higher rate of mydriasis and additional ICH), poor-grade aSAH patients with PDC achieve favorable outcome in a significant number of patients. Therefore, treatment and PDC should not be omitted in this severely ill patient collective. Prospective controlled studies are warranted.


Two cases of tularemia in hunters from rural Newfoundland.
Tularemia is a rare zoonosis caused by Francisella tularensis, a small gram-negative intracellular coccobacillus. Transmission occurs through direct contact with small mammals such as hares and rabbits, exposure to ticks, or ingestion or inhalation of aerosolized particles. It is a highly variable disease with six subtypes based on clinical features. Tularemia is a very rare disease in Canada, with only 0.01 cases per 100,000 people reported in 2017. In this case report, we describe two cases of tularemia affecting hunters from rural Newfoundland and Labrador. The first case describes a patient with glandular tularemia diagnosed with serology; the second describes a patient with typhoidal tularemia diagnosed on blood culture. Both patients recovered after treatment with gentamicin. These cases highlight the importance of eliciting a careful social history from patients presenting with an unexplained febrile illness. Tularemia should be considered in the differential diagnosis of fever after hunting in rural areas.


Molecular Detection and Identification of Piroplasm in Cattle from Kathmandu Valley, Nepal.
Tick-borne protozoan parasites (TBPPs) cause significant problems for domestic animals' health in Nepal. TBPPs are routinely diagnosed by labor-intensive blood smear microscopy. In Nepal, there are some reports of Babesia and Theileria in cattle, although species identification is rarely performed. Therefore, we performed conventional nested PCR (nPCR) followed by sequence analysis to identify TBPP species infecting cattle in Nepal. One hundred and six blood samples were collected from cattle in the Kathmandu Valley. Thin blood smears were prepared for microscopic examination. Parasite DNA was extracted from the blood, and nPCR and sequencing were performed to identify the TBPPs present. Among the 106 samples, 45 (42.5%) were positive for piroplasm (Babesia spp. and Theileria spp.) via microscope observation and 56 (52.8%) samples were positive via nPCR. The obtained PCR products were used for direct sequencing, and we identified the species as B. bigemina, B. bovis, T. annulate and T. orientalis. Phylogenetic analyses showed that the B. bovis, B. bigemina and T. orientalis sequences from this study belonged to each species clade. On the other hand, T. annulate was divided into two clades in the analysis, and our T. annulate sequences were also divided in these two clades. The piroplasm-positive cattle showed lower hemoglobin and red blood cells than healthy cattle. To the best of our knowledge, this study is the first to apply molecular detection and species determination of TBPPs in cattle in Nepal. The results of this study may be used as a starting point for the development of successful TBPP surveillance and prevention programs in Nepal.


Spectrum of mutations in CFTR in Finland: 18 years follow-up study and identification of two novel mutations.
The incidence of cystic fibrosis (CF) is low in the isolated Finnish population and the Finnish CF mutation spectrum has differed from many European countries. We have analyzed the mutation spectrum and the geographical distribution of CF mutations in Finland covering the last 18 years (1987-2004). A total of 14 mutations were identified; two of them new, 774insT and S589T (G>C at 1,898). The overall coverage of mutations was 97% (99/102 chromosomes). The most frequent mutations were F508del and 394delTT, found in 36% (37/102) and 35% (36/102) of the CF chromosomes respectively. Of the rare mutations, a mutation of presumable Slavic origin, CFTRdele2.3 (21 kb), was enriched in a rural isolate with a frequency of 5,9% (6/102), and a mutation that possibly indicates Swedish influence, 3659delC, was scattered throughout the country with a similar frequency of 5,9% (6/102). G542X, R1162X, R117H, 3732delA, 1,898 + 3A >C, S1196X, S945L, W57R, 774insT and S589T were each identified in a number of chromosomes from one to three. Our observations of the Finnish CF mutation spectrum fit well with the characteristics of Finland as a population of multiple local founder effects.