Chiari I malformation: classification and management.
Considerable debate exists about which surgical options are best for the management of the Chiari I malformation. We present a classification system for the Chiari I malformation that improves the prediction of outcome and guides the selection of surgical treatment. Twenty-seven adult patients with Chiari I malformations were grouped on the basis of the presence of signs and symptoms of brain stem compression, syringomyelia, or both. To objectively assess changes in clinical status postoperatively, a scale was developed to quantify the signs and symptoms, which were statistically analyzed by the paired t test. Five patients were asymptomatic and underwent no treatment. Ten patients had symptoms of brain stem compression without associated syringomyelia and underwent brain stem decompression, including anterior decompression in one patient with basilar invagination; all 10 patients had significant improvement at 4-year mean follow-up visits (P < 0.0001). In 12 patients with syringomyelia, 5 were symptomatic from syringomyelia only, 6 were symptomatic from both brain stem compression and syringomyelia, and 1 was symptomatic from brain stem compression only. The median length of symptoms before presentation was longer for patients with syringomyelia than for patients without (2 yr versus 9 mo; P < 0.025); the mean follow-up was 4 years. Surgical procedures included posterior brain stem decompression in 12 patients, plugging of the obex in 7, and placement of syringosubarachnoid shunts in 7, a syringopleural shunt in 1, and fourth ventricular stents in 2. In the 12 patients with syringomyelia, symptoms from brain stem compression dramatically improved with surgical decompression (P < 0.025), whereas symptoms from syringomyelia less dramatically improved or stabilized. The slight improvement or stabilization of syrinx symptoms represents a successful result, given the documented progressive nature of syringomyelia in this group. We conclude that surgical treatment for the Chiari I malformation can stabilize or slightly improve the symptoms attributed to syringomyelia and dramatically relieve the symptoms of brain stem compression. Furthermore, early diagnosis and treatment are critical in obtaining the best outcome for the patient.


Comparison of the properties of two forms of pyruvate kinase in rat liver and determination of their separate activities during development.
1. Two forms of hepatic pyruvate kinase, designated type L and type M, were distinguished on the basis of kinetic, chromatographic, electrophoretic and immunological criteria. They were partially purified and their properties compared with each other and with the purified enzyme from skeletal muscle. 2. In contrast with type L, the type M enzyme showed no marked evidence of co-operative interactions with phosphoenolpyruvate and was not stimulated by fructose diphosphate. 3. The activity profiles of type L and type M enzymes were determined in developing rat liver by utilizing differences in the kinetic properties of the two forms. The high activity of type M enzyme in the early foetal rat decreased in late gestation and immediately after birth to reach a low value, which remained essentially constant for the remainder of the developmental period. The activity of type L enzyme, in contrast, was low in the early foetal and neonatal liver but increased markedly at the onset of weaning. 4. Possible roles of the two forms of hepatic pyruvate kinase in the control of glycolysis and gluconeogenesis are discussed.


Induction of Oxidative Stress and Cell Death in Neural Cells by Silica Nanoparticles.
Silica nanoparticles (SiNPs) are produced on an industrial scale and used in various fields including health care, because silica is stable, inexpensive, and easy to handle. Despite these benefits, there is concern that exposure to SiNPs may lead to adverse effects in certain types of cells or tissues, such as hemolysis, immune responses, and developmental abnormalities in the brain and developing embryos. Although investigations on the toxicity of SiNPs against neurons are essential for medicinal use, only a few studies have assessed the direct effects of SiNPs on cells derived from the central nervous system. In this study, we investigated the toxic effects of SiNPs on primary cultures of hippocampal cells, using SiNPs with diameters of 10-1500 nm. We showed that treatment with SiNPs caused oxidative stress and cell death. Furthermore, we found that these cytotoxicities were dependent on the particle size, concentration, and surface charge of SiNPs, as well as the treatment temperature. The toxicity was reduced by SiNP surface functionalization or protein coating and by pretreating cells with an antioxidant, suggesting that contact-induced oxidative stress may be partially responsible for SiNP-induced cell death. These data will be valuable for utilizing SiNPs in biomedical applications.


Evaluating the PAS-SIM model using a passive air sampler calibration study for pesticides.
The main objective of this study was to evaluate the performance of a model for simulating the uptake of various pesticides on passive air samplers (PAS). From 2006-2007 a series of PAS using XAD-resin were deployed at Egbert, a rural agricultural site in southern Ontario, Canada, to measure the uptake of pesticides for time periods ranging from two months to one year. A continuous increase in sequestered amounts was observed for most pesticides, except for trifluralin and pendimethalin, which could conceivably be subject to substantial degradation inside the sampler. Continuous low-volume active air samples taken during the same period, along with data on weather conditions, allowed for the simulation of the uptake of the pesticides using the model (PAS-SIM). The modelled accumulation of pesticides on the PAS over the deployment period was in good agreement with the experimental data in most cases (i.e., within a factor of two) providing insight into the uptake kinetics of this type of sampler in the field. Passive sampling rates (PSR, m(3) d(-1)) were determined from the empirical data generated for this study using three different methods and compared with the PSRs generated by the model. Overall, the PAS-SIM model, which is capable of accounting for the influence of temperature and wind variations on PSRs, provided reasonable results that range between the three empirical approaches employed and well-established literature values. Further evaluation and application of the PAS-SIM model to explore the potential spatial and temporal variability in PAS uptake kinetics is warranted, particularly for established monitoring sites where detailed meteorological data are more likely to be available.


Health literacy of older drivers and the importance of health experience for self-regulation of driving behaviour.
This study provides much needed information on the education level of older drivers regarding the impact of health conditions and medications on personal driving safety, where they source this information, and how this knowledge influences self-regulation of driving. Random and convenience sampling secured 322 Australian drivers (63.9% males) aged 65 years and over (M = 77.35 years, SD = 7.35) who completed a telephone interview. The majority of respondents (86%) had good knowledge about health conditions (health knowledge) and driving safety, however more than 50% was classified as having poor knowledge on the effects of certain medications (medication knowledge) and driving safety. Poorer health knowledge was associated with a reduced likelihood of driving over 100 km in adjusted models. Being older and having more than one medical condition was found to increase the likelihood of self-regulation of driving. Results indicate that health knowledge was less important for predicting driving behaviour than health experience. Of great interest was that up to 85.7% of respondents reported not receiving advice about the potential impact of their medical condition and driving from their doctor. The findings indicate a need for improved dissemination of evidence-based health information and education for older drivers and their doctors.


Magnesium effects on activation of skinned fibers from striated muscle.
The intracellular Ca movements that control contraction and relaxation of striated muscle are regulated by the membrane potential and influenced by Mg2+. In skinned fibers, the internal composition can be manipulated directly by Ca movements estimated from isometric force transients, net changes in sarcoplasmic reticulum (SR) Ca, and 45Ca flux between fiber and bath. Stimulated Ca release, unlike unstimulated 45Ca efflux at low external [Ca2+], is highly [Mg2+]-sensitive at 20 C. Force and tracer measurements indicate three major sites of Mg2+-Ca2+ interaction in situ: Mg2+ can stimulate the SR active Ca transport system, inhibit a Ca2+-dependent Ca efflux pathway of SR, and shift the force-[Ca2+] relation, presumably by reducing Ca2+ binding to myofilament regulatory sites. These mechanisms constrain the resting Ca flux and are adaptive during relaxation. However, analysis of CI-stimulated 45Ca release and reaccumulation suggests that the depolarization process may inhibit Mg2+-dependent Ca influx, the membrane potential controlling both efflux and influx; recent studies on voltage-clamped cut fibers support this hypothesis. The Ca2+ and Mg2+ dependence of caffeine-stimulated 45Ca efflux suggests that Mg2+ inhibition of the Ca2+-dependent efflux pathway is small during rapid Ca2+ efflux. Therefore, both Mg2+ mechanisms, which minimize net release, may be reversed during normal activation.


Potential global distribution of Aleurocanthus woglumi considering climate change and irrigation.
Citrus blackfly, Aleurocanthus woglumi Ashby (Hemiptera: Aleyrodidae), is an important agricultural quarantine pest, causing substantial economic losses to citrus and many other cultivated crops. Aleurocanthus woglumi is found in tropical and subtropical regions but is presently unknown in Europe and the Mediterranean Basin. We used CLIMEX to model the potential distribution of A. woglumi under an historical climate scenario (centred on 1995), including a spatially explicit irrigation scenario. We found that A. woglumi could potentially invade the Mediterranean Basin, and south-east Asia, including Australia. There is potential for it to invade most of sub-Saharan Africa. Irrigation is revealed as an important habitat factor affecting the potential distribution of A. woglumi, increasing its potential range by 53% in Asia. Under a future climate scenario for 2050, its potential distribution increased across all continents except Africa, where potential range expansion due to relaxation of cold stresses was limited, and was offset by range decrease due to lethal heat or dry stress. As global climates warm, Europe is likely to face a substantial increase in the area at risk of establishment by A. woglumi (almost doubling under the 2050 irrigation scenario). The biosecurity threat from A. woglumi is significant in current citrus production areas and poses a challenge to biosecurity managers and risk analysts.


Salivary Cytokines in Children with Nephrotic Syndrome versus Healthy Children: A Comparative Study.
The aims of this study were to compare salivary cytokines and total protein between children with nephrotic syndrome (NS) and healthy children, and to examine whether saliva parameters can differentiate between steroid sensitivity and resistance and between disease remission and relapse. Twenty-seven children with nephrotic syndrome were classified according to steroid sensitivity and resistance, and disease remission and relapse. Twenty healthy children served as controls. Whole saliva samples were collected from all the participants. Urine and blood tests done on the same day as the saliva collection were recorded. Salivary total protein was quantified using bicinchoninic acid and IFNγ, IL-4, IL-8, IL-6, and IL1β levels using ELISA. The mean ages of the nephrotic syndrome and control groups were 11.3 ± 2.4 and 9 ± 4.2, respectively. Compared to the control group, for the nephrotic syndrome group, total salivary protein was significantly lower, as were the levels of all the cytokines examined except IFNγ. Statistically significant differences were not found in any of the salivary markers examined between the children with nephrotic syndrome who were treatment sensitive (n = 19) and resistant (n = 8). Protein and IL-8 salivary levels were lower in the active (n = 7) than in the remission (n = 20) group. Salivary parameters distinguished children with nephrotic syndrome in relapse from healthy children. This may be due to decreased salivary protein excretion, which reflects decreased plasma levels, consequent to proteinuria. Accordingly, salivary markers may be developed as a diagnostic or screening tool for NS activity.


Evidence that cleavage of the thyrotropin receptor involves a "molecular ruler" mechanism: deletion of amino acid residues 305-320 causes a spatial shift in cleavage site 1 independent of amino acid motif.
Some TSH receptors (TSHR) on the cell surface cleave into A and B subunits. Cleavage at upstream Site 1 is followed by the proteolytic excision of an intervening C peptide region terminating at a downstream Site 2. Although present evidence suggests that Site 1 lies between amino acid residues 303 and 317, the mechanism and exact amino acid(s) involved in cleavage are unknown. Previous amino acid substitutions at Site 1 failed to abrogate cleavage. We, therefore, performed deletion mutations within this region. Cleavage of cell surface TSHR, detected by 125I-TSH cross-linking to intact cells, was not prevented by deletion of four individual segments within the Site 1 cleavage region (delta305-308, delta309-312, delta313-316, delta317-320). However, deletion of the entire region (delta305-320) reduced the extent of cleavage and shifted the cleavage site upstream of the glycan at amino acid residue N302. Elimination of this glycan (N302Q substitution) reversed the effect of deleting amino acid residues 305-320 on TSHR cleavage, suggesting that reduced cleavage at the new, upstream cleavage site was caused by steric hindrance by the glycan at N302. In summary, deletion, as opposed to mutagenesis, of the TSHR cleavage Site 1 region produces a spatial shift in TSHR cleavage Site 1 from downstream to upstream of the glycan at N302. These observations provide strong evidence that TSHR cleavage at this site does not occur at a particular amino acid motif and suggests that cleavage involves a "molecular ruler" mechanism involving cleavage at a fixed distance from a protease attachment site.


The sequence specificity domain of cytosine-C5 methylases.
Prokaryotic DNA[cytosine-C5]methyltransferases (m5C-methylases) share a common architectural arrangement of ten conserved sequence motifs. A series of eleven hybrids have been constructed between the HpaII (recognition sequence: Cm5CGG) and HhaI (recognition sequence: Gm5CGC) DNA-methylases. The hybrids were over-expressed in E.coli and their in vivo methylation phenotypes investigated. Six were inactive by our assay while five of them retained partial methylation activity and full specificity. In all five cases the specificity matched that of the parent methylase which contributed the so-called variable region, located between conserved motifs VIII and IX. This was the only sequence held in common between the active hybrids and for the first time provides unequivocal evidence that the specificity determinants of the mono-specific m5C-methylases are located within the variable region. Correlation of the hybrid methylase structure with the efficiency of methylation suggests that conserved motif IX may interact with the variable region whereas motif X most probably interacts with the N-terminal half of the molecule.


Renal haemodynamic and protective effects of renoactive drugs in type 2 diabetes: Interaction with SGLT2 inhibitors.
Diabetic kidney disease remains the leading cause of end-stage kidney disease and a major risk factor for cardiovascular disease. Large cardiovascular outcome trials and dedicated kidney trials have shown that sodium-glucose cotransporter (SGLT)2 inhibitors reduce cardiovascular morbidity and mortality and attenuate hard renal outcomes in patients with type 2 diabetes (T2D). Underlying mechanisms explaining these renal benefits may be mediated by decreased glomerular hypertension, possibly by vasodilation of the post-glomerular arteriole. People with T2D often receive several different drugs, some of which could also impact the renal vasculature, and could therefore modify both renal efficacy and safety of SGLT2 inhibition. The most commonly prescribed drugs that could interact with SGLT2 inhibitors on renal haemodynamic function include renin-angiotensin system inhibitors, calcium channel blockers and diuretics. Herein, we review the effects of these drugs on renal haemodynamic function in people with T2D and focus on studies that measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) with gold-standard techniques. In addition, we posit, based on these observations, potential interactions with SGLT2 inhibitors with an emphasis on efficacy and safety.


High expression of CCL20 is associated with poor prognosis in patients with hepatocellular carcinoma after curative resection.
Chemokine ligand 20 (CCL20) plays an important role in the carcinogenesis, invasion, and progression of malignancies. This study aimed to investigate the prognostic significance of CCL20 in patients with hepatocellular carcinoma (HCC) after curative resection. Expression of CCL20 was evaluated by immunohistochemistry in tumor tissue from 125 patients who underwent curative resection of HCC. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of HCC patients. CCL20 expression was verified in all tumor specimens. CCL20 expression was associated with tumor size (P = 0.002), tumor number (P = 0.031), vascular invasion (P = 0.003), tumor differentiation (P = 0.024), and tumor recurrence (P < 0.001). Patients with high CCL20 expression had poorer recurrence-free survival and overall survival (both P < 0.001) than those with low CCL20 expression. Multivariate analysis showed CCL20 expression was an independent predictor of tumor recurrence (Hazard ratio 3.934, P = 0.002), recurrence-free survival (Hazard ratio 2.573, P = 0.001), and overall survival (Hazard ratio 2.930, P = 0.001). CCL20 expression was associated with tumor recurrence and survival of HCC patients. It may be used to predict prognosis of patients with HCC and may be a new target of postoperative adjuvant therapy.


Reversal of cystoid macular edema in gyrate atrophy patients.
This study reports the presentation of two families with gyrate atrophy (GA). The aim of this study was to characterize the potential effect of therapeutic regimens on macular edema. Two unrelated patients with GA were studied for the potential effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500 mg/day), on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings. Blood samples for DNA, mRNA, and exons of the OAT gene were screened for mutations and splicing effect when relevant. At presentation, both patients manifested typical ophthalmic features of GA including cystoid macular edema (CME). One patient also exhibited optic nerve head hamartoma. Following treatment ornithine levels have lessened, BCVA improved, and central macular thickness (CMT) markedly decreased in all four studied eyes. The molecular pathologic features included a novel splice site mutation (c.900+1G>A). We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.


Study of the ^{26}Al^{m}(d,p)^{27}Al Reaction and the Influence of the ^{26}Al 0^{+} Isomer on the Destruction of ^{26}Al in the Galaxy.
The existence of ^{26}Al (t_{1/2}=7.17×10^{5} yr) in the interstellar medium provides a direct confirmation of ongoing nucleosynthesis in the Galaxy. The presence of a low-lying 0^{+} isomer (^{26}Al^{m}), however, severely complicates the astrophysical calculations. We present for the first time a study of the ^{26}Al^{m}(d,p)^{27}Al reaction using an isomeric ^{26}Al beam. The selectivity of this reaction allowed the study of ℓ=0 transfers to T=1/2, and T=3/2 states in ^{27}Al. Mirror symmetry arguments were then used to constrain the ^{26}Al^{m}(p,γ)^{27}Si reaction rate and provide an experimentally determined upper limit of the rate for the destruction of isomeric ^{26}Al via radiative proton capture reactions, which is expected to dominate the destruction path of ^{26}Al^{m} in asymptotic giant branch stars, classical novae, and core collapse supernovae.


Disruption of the apelin-APJ system worsens hypoxia-induced pulmonary hypertension.
The G-protein-coupled receptor APJ and its ligand apelin are highly expressed in the pulmonary vasculature, but their function in this vascular bed is unclear. We hypothesized that disruption of apelin signaling would lead to worsening of the vascular remodeling associated with pulmonary hypertension (PH). We found that apelin-null mice developed more severe PH compared with wild-type mice when exposed to chronic hypoxia. Micro-computed tomography of the pulmonary arteries demonstrated significant pruning of the microvasculature in the apelin-null mice. Apelin-null mice had a significant reduction of serum nitrate levels. This was secondary to downregulation of endothelial nitric oxide synthase (eNOS), which was associated with reduced expression of Kruppel-like factor 2 (KLF2), a known regulator of eNOS expression. In vitro knockdown studies targeting apelin in human pulmonary artery endothelial cells demonstrated decreased eNOS and KLF2 expression, as well as impaired phosphorylation of AMP-activated kinase and eNOS. Moreover, serum apelin levels of patients with PH were significantly lower than those of controls. These data demonstrate that disruption of apelin signaling can exacerbate PH mediated by decreased activation of AMP-activated kinase and eNOS, and they identify this pathway as a potentially important therapeutic target for treatment of this refractory human disease.


The effect of electrical stimulation and ouabain on the uptake and efflux of L-[U-14C] valine in chopped tissue from guinea-pig cerebral cortex.
1. Chopped tissue from guinea-pig cerebral cortex carried out an energy-dependent accumulation of l-[(14)C]valine. 2. The uptake was dependent on the extracellular concentration of Na(+) and was markedly inhibited by ouabain (20mum). The extent of the inhibition of uptake by ouabain was also Na(+)-dependent. 3. The accumulation of labelled valine was not directly dependent on the ATP and creatine phosphate contents of the slices. 4. Electrical stimulation increased the rate of [(14)C]valine uptake at first but ultimately led to a net loss of the label so that the amount of label present in the tissue was lower than in the controls. 5. The rate of loss of label during prolonged stimulation was dependent on the extracellular concentration of Na(+). 6. The efflux of labelled valine from slices preloaded at 164mm-Na(+) was studied at 164, 80 and 40mm-Na(+) with and without electrical stimulation or ouabain. 7. Lowering the Na(+) concentration or adding ouabain increased the rate of efflux. 8. Electrical stimulation had little effect on the rate of efflux at first but ultimately led to a more complete loss of label from the tissue than occurred in the control. A kinetic analysis of the efflux curves was attempted.


Prostate cancer cells specifically reorganize epithelial cell-fibroblast communication through proteoglycan and junction pathways.
Microenvironment and stromal fibroblasts are able to inhibit tumor cell proliferation both through secreted signaling molecules and direct cell-cell interactions but molecular mechanisms of these effects remain unclear. In this study, we investigated a role of cell-cell contact-related molecules (protein ECM components, proteoglycans (PGs) and junction-related molecules) in intercellular communications between the human TERT immortalized fibroblasts (BjTERT fibroblasts) and normal (PNT2) or cancer (LNCaP, PC3, DU145) prostate epithelial cells. It was shown that BjTERT-PNT2 cell coculture resulted in significant decrease of both BjTERT and PNT2 proliferation rates and reorganization of transcriptional activity of cell-cell contact-related genes in both cell types. Immunocytochemical staining revealed redistribution of DCN and LUM in PNT2 cells and significant increase of SDC1 at the intercellular contact zones between BjTERT and PNT2 cells, suggesting active involvement of the PGs in cell-cell contacts and contact inhibition of cell proliferation. Unlike to PNT2 cells, PC3 cells did not respond to BjTERT in terms of PGs expression, moderately increased transcriptional activity of junctions-related genes (especially tight junction) and failed to establish PC3-BjTERT contacts. At the same time, PC3 cells significantly down-regulated junctions-related genes (especially focal adhesions and adherens junctions) in BjTERT fibroblasts resulting in visible preference for homotypic PC3-PC3 over heterotypic PC3-BjTERT contacts and autonomous growth of PC3 clones. Taken together, the results demonstrate that an instructing role of fibroblasts to normal prostate epithelial cells is revoked by cancer cells through deregulation of proteoglycans and junction molecules expression and overall disorganization of fibroblast-cancer cell communication.


Standard vs Distal Roux-en-Y Gastric Bypass in Patients With Body Mass Index 50 to 60: A Double-blind, Randomized Clinical Trial.
Up to one-third of patients undergoing bariatric surgery have a body mass index (BMI) of more than 50. Following standard gastric bypass, many of these patients still have a BMI greater than 40 after peak weight loss. To assess the efficacy and safety of standard gastric bypass vs distal gastric bypass in patients with a BMI of 50 to 60. Double-blind, randomized clinical parallel-group trial at 2 tertiary care centers in Norway (Oslo University Hospital and Vestfold Hospital Trust) between May 2011 and April 2013. The study included 113 patients with a BMI of 50 to 60 aged 20 to 60 years. The 2-year follow-up was completed in May 2015. Standard gastric bypass (alimentary limb, 150 cm) and distal gastric bypass (common channel, 150 cm), both with a biliopancreatic limb of 50 cm and a gastric pouch of about 25 mL. Primary outcome was the change in BMI from baseline until 2 years after surgery. Secondary outcomes were cardiometabolic risk factors, nutritional outcomes, adverse events, gastrointestinal symptoms, and health-related quality of life. At baseline, the mean age of the patients was 40 years (95% CI, 38-41 years), 65% were women, mean BMI was 53.5 (95% CI, 52.9-54.0), and mean weight was 158.8 kg (95% CI, 155.3-162.3 kg). The mean reduction in BMI was 17.8 (95% CI, 16.9-18.6) after standard gastric bypass and 17.2 (95% CI, 16.3-18.0) after distal gastric bypass, and the mean between-group difference was 0.6 (95% CI, -0.6 to 1.8; P = .32). Reductions in mean levels of total and low-density lipoprotein cholesterol were greater after distal gastric bypass than standard gastric bypass, and between-group differences were 19 mg/dL (95% CI, 11-27 mg/dL ) and 28 mg/dL (95% CI, 21 to 34 mg/dL), respectively (P < .001 for both). Reductions in fasting glucose levels and hemoglobin A1c were greater after distal gastric bypass. Secondary hyperparathyroidism and loose stools were more frequent after distal gastric bypass. The number of adverse events and changes in health-related quality of life did not differ between the groups. Importantly, 1 patient developed liver failure and 2 patients developed protein-caloric malnutrition treated by elongation of the common channel following distal gastric bypass. Distal gastric bypass was not associated with a greater BMI reduction than standard gastric bypass 2 years after surgery. However, we observed different changes in cardiometabolic risk factors and nutritional markers between the groups. Clinicaltrials.gov Identifier: NCT00821197.


Inflammatory Bowel Disease in Primary Immunodeficiencies.
Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.


Abnormality classification and localization using dual-branch whole-region-based CNN model with histopathological images.
The task of classification and localization with detecting abnormalities in medical images is considered very challenging. Computer-aided systems have been widely employed to address this issue, and the proliferation of deep learning network architectures is proof of the outstanding performance reported in the literature. However, localizing abnormalities in regions of images that can support the confidence of classification continues to attract research interest. The difficulty of using digital histopathology images for this task is another drawback, which needs high-level deep learning models to address the situation. Successful pathology localization automation will support automatic acquisition planning and post-imaging analysis. In this paper, we address issues related to the combination of classification with image localization and detection through a dual branch deep learning framework that uses two different configurations of convolutional neural networks (CNN) architectures. Whole-image based CNN (WCNN) and region-based CNN (RCNN) architectures are systematically combined to classify and localize abnormalities in samples. A multi-class classification and localization of abnormalities are achieved using the method with no annotation-dependent images. In addition, seamless confidence and explanation mechanism is provided so that outcomes from WCNN and RCNN are mapped together for further analysis. Using images from both BACH and BreakHis databases, an exhaustive set of experiments was carried out to validate the performance of the proposed method in achieving classification and localization simultaneously. Obtained results showed that the system achieved a classification accuracy of 97.08%, a localization accuracy of 94%, and an area under the curve (AUC) of 0.10 for classification. Further findings from this study revealed that a multi-neural network approach could provide a suitable method for addressing the combinatorial problem of classification and localization anomalies in digital medical images. Lastly, the study's outcome offers means for automating the annotation of histopathology images and the support for human pathologists in locating abnormalities.


Haemoglobin J-Biskra: a new mildly unstable alpha1 gene variant with a deletion of eight residues (alpha50-57, alpha51-58 or alpha52-59) including the distal histidine.
Single point mutation, which accounts for 92% of the 700 known variants, is the most frequent genetic defect responsible for abnormal haemoglobins. Small deletions (or insertions) involving from one to five residues are also observed, but in only approximately 5% of cases. The remaining variants produce fusion or extended haemoglobins. A deletion of eight residues, which included the distal histidine and its neighbours (alpha50-57, alpha51-58 or alpha52-59), was found in Hb J-Biskra. This new alpha-chain variant was mildly unstable in vitro only and there was no haematological or biochemical evidence of haemolysis in the affected family members. 24 nucleotides were missing in a region of the alpha1 gene showing an identical sequence of eight nucleotides at both ends. Several starting points could therefore lead to the same nucleotide and aminoacid remaining sequence. This deletion is the largest up to now reported in a haemoglobin molecule which is expressed at an almost normal level in the red blood cell. Comparison of the DNA sequences near to the deleted (or inserted) regions in the various haemoglobins carrying this type of abnormality almost always revealed the presence of a sequence that was hypothesized to slow down progression of the replication fork, and of repeats that may lead to possible secondary structures favouring slipped mispairing.


[Effect of cardiac glycosides on whole body potassium concentration in circulatory insufficiency].
Variation of potassium levels produced by cardiac glycosides was assessed in patients with 1st- to 3d-stage circulatory insufficiency, by means of 40K radioactivity measurement in a low radioactivity background chamber. Total group figures demonstrated that total body potassium levels increased with the improvement of the patients' clinical condition. Total body potassium decreased in patients showing signs of cardiac glycoside intoxication. The analysis of the data with reference to pre-and post-treatment baseline tissue potassium concentrations, as compared to the desired level, showed tissue potassium to normalize under the effect of cardiac glycosides in cases of initially abnormal values, and to decrease irrespective of the initial values in cases of cardiac glycoside intoxication.


Pruritus in pediatric burn survivors: defining the clinical course.
Pruritus is a frequent and severe symptom and a significant cause of distress for adult burn patients. Its effects in children are largely unstudied. The aim of this study is to characterize postburn itch in the pediatric population. This is a retrospective review from 2006 to 2013 for pediatric burn survivors who were enrolled in a longitudinal multicenter outcomes study. Demographic data, injury characteristics, associated symptoms (skin-related problems, pain, and sleep), and incidence and intensity (Numerical Rating Scale) of itch were examined. Measures were completed at hospital discharge and at 6, 12, and 24 months after injury. Spearman's correlations were used to examine the correlation between itch intensity and associated symptoms. Multivariate regression analyses examined the impact of associated symptoms on itch intensity. There were 430 pediatric burn survivors with a mean age of 7.8 years and a mean TBSA of 40.8%. Pruritus is present in most children (93%) and is of moderate intensity (5.7 ± 3.1) at discharge. The frequency and intensity of pruritus decreases over time; a majority of children continue to report symptoms at 2 years (63%). Itch was significantly correlated with associated symptoms. Regression analyses showed a correlation between itch intensity and pain at each time point. There was no association between itch intensity and burn etiology, age, gender, or burn size. Pruritus is a frequent complication that lasts for at least 2 years after injury in a majority of pediatric burn survivors. This information will enable better tracking of outcomes and will serve as a baseline for assessing interventions.


Long-term Outcomes of Induction Carboplatin and Gemcitabine Followed by Concurrent Radiotherapy With Low-dose Paclitaxel and Gemcitabine for Stage III Non-small-cell Lung Cancer.
Standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemo-radiation (CRT). A regimen of induction carboplatin and gemcitabine followed by CRT was developed at the McGill University Health Centre to prevent delays in treatment initiation. We report the long-term outcomes with this regimen based on a pooled analysis of both protocol patients from a phase II study and nonprotocol patients. Outcomes and toxicity data were retrieved for 142 patients with stage III NSCLC: 43 patients treated on protocol between January 2003 and November 2004, and 101 patients treated off-protocol between December 2004 and August 2013. Patients received 2 cycles of carboplatin with an area under the curve of 5 intravenously (IV) on day 1 and gemcitabine 1000 mg/m2 IV on days 1 and 8 every 3 weeks, followed on day 50 by CRT, 60 Gy/30 over 6 weeks, concomitantly with 2 cycles of paclitaxel 50 mg/m2 IV and gemcitabine 100 mg/m2 IV on days 1 and 8 every 3 weeks. The median overall survival was 23.2 months. With a median follow-up of 23.8 months, the 3-, 4-, and 5-year overall survival was 38%, 30%, and 26%, respectively. The median and 5-year progression-free survival rates were 12.5 months and 25%, respectively. Rates of grade ≥ 3 hematologic, esophageal, and respiratory toxicity were 20%, 10%, and 10%, respectively. Forty-eight patients received further lines of chemotherapy. The present analysis affirms the favorable toxicity profile of this novel induction chemotherapy, without apparent compromise in clinical outcomes, when compared with regimens using immediate concurrent CRT.


Characterization of the Disinfectant Resistance Genes qacEΔ1 and cepA in Carbapenem-Resistant Klebsiella pneumoniae Isolates.
The emergence and wide global spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are of great concern. This multicenter study aimed to investigate the molecular characteristics of CRKP isolates from inpatients in Wuhan, China. From June 2018 to March 2019, 74 nonduplicated CRKP clinical isolates were collected from six hospitals in Wuhan. We determined the minimum inhibitory concentrations of 18 antibiotics and used real-time polymerase chain reaction to detect the presence of disinfectant resistance genes qacEΔ1 and cepA. Pulsed-field gel electrophoresis was conducted to assess the genetic relatedness of isolates. Among the 74 CRKP isolates, the rates of resistance to carbapenems were high: 93.2% to ertapenem, 90.5% to imipenem, and 87.8% to meropenem. All isolates were resistant to at least one carbapenem antibiotic. Of the 74 isolates, 64.9% (48/74) were positive for qacEΔ1 and 93.2% (69/74) for cepA. QacEΔ1 and cepA were detected concomitantly in 46 isolates (62.2%), whereas only 4.1% (3/74) had no disinfectant resistance genes. Pulsed-field gel electrophoresis analysis clustered the 46 CRKP strains co-producing qacEΔ1 and cepA into 15 different clonal clusters (Types A to O). The most common clonal clusters were Type C (41.3%), Type E (13.0%), and Type J (8.7%). The study showed high rates of resistance to most antibiotics and high frequency of qacEΔ1 and cepA in CRKP isolates. Specific clonal dissemination of CRKP was detected within the same hospital or between different hospitals. Therefore, medical institutions should choose and use disinfectants correctly to prevent the spread of CRKP.


Cisplatin@US-tube carbon nanocapsules for enhanced chemotherapeutic delivery.
The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have also garnered attention in the area of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of a new ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectrometry (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 °C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic-F108 surfactant. Finally, the anticancer activity of pluronic-wrapped CDDP@US-tubes has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP after 24 h. These studies have laid the foundation for developing US-tube-based delivery of chemotherapeutics, with drug release mainly limited to within cancer cells only.


Impact of Pain, Opioids, and the Mu-opioid Receptor on Progression and Survival in Patients With Newly Diagnosed Stage IV Pancreatic Cancer.
Pancreatic adenocarcinoma is frequently associated with pain requiring opioid therapy. Opioids, however, have been implicated in causing tumor progression, ultimately shortening survival. We examined the impact of pain, opioid use, and the mu-opioid receptor (MOP-R) expression in tumor tissue on progression-free survival and overall survival of patients with metastatic pancreatic cancer. We identified 103 patients with metastatic pancreatic adenocarcinoma receiving chemotherapy and abstracted data from Tumor Registry, in addition to pain, opioid exposure, carbohydrate antigen 19-9 values, survival, and imaging response. MOP-R expression was evaluated using an immunohistochemistry assay. The association of variables with progression-free survival and overall survival was analyzed in univariate and multivariate models. Patients with low opioid use (<5 mg oral morphine equivalent/d) survived longer than patients with high opioid (HO) use (≥5 mg oral morphine equivalent/d) (median overall survival of 315 vs. 150 d; hazard ratio [HR]=1.79; 95% confidence interval [CI]: 1.13, 2.84). This effect persisted on multivariate models (adjusted HR=2.76; 95% CI: 1.39, 5.48). Low opioid patients tended to respond better to treatment than HO patients, based on carbohydrate antigen 19-9. Patients with low MOP-R expression had longer median survival (230 vs. 193 d), though the HR was not significant (1.15; 95% CI: 0.71, 1.88). Baseline pain was not associated with outcomes. In patients with metastatic pancreatic adenocarcinoma, HO use is associated with decreased survival, but the severity of baseline pain and MOP-R expression score in tumor tissue does not correlate with clinical outcomes.


Tracheo-oesophageal fistula from blunt trauma. A case report.
Tracheo-oesophageal fistula is a rare complication of blunt trauma; by 1980 only 35 cases had been recorded. Presentation is usually delayed and the initial trauma severe. Fractures, pneumothorax, haemoptysis and surgical emphysema are not invariable features. Mediastinitis is rare, and surgical management is usually successful. The site of the fistula in the posterior wall of the trachea proximal to the main carina is remarkably constant. The membranous trachea is probably lacerated at the time of injury and the oesophageal wall contused. The contusion progresses to necrosis and a fistula is formed.


RNA interference-based antiviral immune response against the salivary gland hypertrophy virus in Glossina pallidipes.
Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; Hytrosaviridae) is a non-occluded dsDNA virus that specifically infects the adult stages of the hematophagous tsetse flies (Glossina species, Diptera: Glossinidae). GpSGHV infections are usually asymptomatic, but unknown factors can result to a switch to acute symptomatic infection, which is characterized by the salivary gland hypertrophy (SGH) syndrome associated with decreased fecundity that can ultimately lead to a colony collapse. It is uncertain how GpSGHV is maintained amongst Glossina spp. populations but RNA interference (RNAi) machinery, a conserved antiviral defense in insects, is hypothesized to be amongst the host's mechanisms to maintain the GpSGHV in asymptomatic (persistent or latent) infection state. Here, we investigated the involvement of RNAi during GpSGHV infections by comparing the expression of three key RNAi machinery genes, Dicer (DCR), Argonaute (AGO) and Drosha, in artificially virus injected, asymptomatic and symptomatic infected G. pallidipes flies compared to PBS injected (controls) individuals. We further assessed the impact of AGO2 knockdown on virus infection by RT-qPCR quantification of four selected GpSGHV genes, i.e. odv-e66, dnapol, maltodextrin glycosyltransferase (a tegument gene) and SGHV091 (a capsid gene). We show that in response to hemocoelic injections of GpSGHV into G. pallidipes flies, increased virus replication was accompanied by significant upregulation of the expression of three RNAi key genes; AGO1, AGO2 and DCR2, and a moderate increase in the expression of Drosha post injection compared to the PBS-injected controls. Furthermore, compared to asymptomatically infected individuals, symptomatic flies showed significant downregulation of AGO1, AGO2 and Drosha, but a moderate increase in the expression of DCR2. Compared to the controls, knockdown of AGO2 did not have a significant impact on virus infection in the flies as evidenced by unaltered transcript levels of the selected GpSGHV genes. The upregulation of the expression of the RNAi genes implicate involvement of this machinery in controlling GpSGHV infections and the establishment of symptomatic GpSGHV infections in Glossina. These findings provide a strategic foundation to understand GpSGHV infections and to control latent (asymptomatic) infections in Glossina spp. and thereby control SGHVs in insect production facilities.


Concise Review: Liver Regenerative Medicine: From Hepatocyte Transplantation to Bioartificial Livers and Bioengineered Grafts.
Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease and acute liver failure. Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell-derived hepatocyte-like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine. Stem Cells 2017;35:42-50.


Alterations in Neural Control of Constant Isometric Contraction with the Size of Error Feedback.
Discharge patterns from a population of motor units (MUs) were estimated with multi-channel surface electromyogram and signal processing techniques to investigate parametric differences in low-frequency force fluctuations, MU discharges, and force-discharge relation during static force-tracking with varying sizes of execution error presented via visual feedback. Fourteen healthy adults produced isometric force at 10% of maximal voluntary contraction through index abduction under three visual conditions that scaled execution errors with different amplification factors. Error-augmentation feedback that used a high amplification factor (HAF) to potentiate visualized error size resulted in higher sample entropy, mean frequency, ratio of high-frequency components, and spectral dispersion of force fluctuations than those of error-reducing feedback using a low amplification factor (LAF). In the HAF condition, MUs with relatively high recruitment thresholds in the dorsal interosseous muscle exhibited a larger coefficient of variation for inter-spike intervals and a greater spectral peak of the pooled MU coherence at 13-35 Hz than did those in the LAF condition. Manipulation of the size of error feedback altered the force-discharge relation, which was characterized with non-linear approaches such as mutual information and cross sample entropy. The association of force fluctuations and global discharge trace decreased with increasing error amplification factor. Our findings provide direct neurophysiological evidence that favors motor training using error-augmentation feedback. Amplification of the visualized error size of visual feedback could enrich force gradation strategies during static force-tracking, pertaining to selective increases in the discharge variability of higher-threshold MUs that receive greater common oscillatory inputs in the β-band.


Review of evidence for bosentan therapy for treatment of Eisenmenger syndrome.
Eisenmenger syndrome (ES) is a rare condition caused by a right-to-left cyanotic shunt. To date, only heart-lung transplant has been shown to be curative. Bosentan is the only medication studied with a double-blind placebo-controlled randomized trial for management of this condition. The intent of this article is to explore the literature surrounding bosentan in ES and assess its efficacy. A literature review was conducted with no limitation on date. Titles were scanned for applicability, and abstracts of those articles found to be pertinent were reviewed. Those articles considered relevant based on the abstract were read in entirety. Eisenmenger syndrome remains incurable except through heart-lung transplant. Although no specific medical treatment or algorithm exists, three pharmacological classes show promise in disease management: endothelin receptor antagonists, phosphodiesterase inhibitors, and prostacyclins. Combined therapy with these agents may improve cardiopulmonary function. Bosentan has not been proven as a monotherapy for ES and is not appropriate in all patients as side effects are commonly reported. Further study is required to assess efficacy of combination therapy and utilization as a bridge to transplant or surgical correction of the underlying defect.


Sustainable construction: composite use of tyres and ash in concrete.
An investigation was carried out to establish the physical, mechanical and chemical characteristics of a non-standard (unprocessed) pulverised fuel ash (PFA) and waste tyres from a former landfill site at the Power Station Hill near Church Village, South Wales, United Kingdom. Investigations are on-going to establish the suitability of the fly ash and/or tyres in road construction (embankment and pavement) and also in concrete to be used in the construction of the proposed highway. This paper reports on concrete-based construction where concrete blends (using various levels of PFA as partial replacement for Portland cement (PC), and shredded waste tyres (chips 15-20mm) as aggregate replacement) were subjected to unconfined compressive strength tests to establish performance, hence, optimising mix designs. Strength development up to 180 days for the concrete made with PC-PFA blends as binders (PC-PFA concrete), with and without aggregate replacement with tyre chips, is reported. The binary PC-PFA concrete does not have good early strength but tends to improve at longer curing periods. The low early strength observed means that PC-PFA concrete cannot be used for structures, hence, only as low to medium strength applications such as blinding, low-strength foundations, crash barriers, noise reduction barriers, cycle paths, footpaths and material for pipe bedding.


Sexually dimorphic fin regeneration in zebrafish controlled by androgen/GSK3 signaling.
Certain fish and amphibians regenerate entire fins and limbs after amputation, whereas such potential is absent in birds and limited in mammals to digit tips [1, 2]. Additionally, regenerative success can change during life stages. Anuran tadpoles gradually lose the capacity to regenerate limbs [3, 4], and digit regeneration occurs more effectively in fetal mice and human children than adults [5-8]. Little is known about mechanisms that control regenerative capacity. Here, we identify an unexpected difference between male and female zebrafish in the regenerative potential of a major appendage. Males display regenerative defects in amputated pectoral fins, caused by impaired blastemal proliferation. This regenerative failure emerges after sexual maturity, is mimicked in androgen-treated females, and is suppressed in males by androgen receptor antagonism. Androgen signaling maintains expression of dkk1b and igfbp2a, which encode secreted inhibitors of Wnt and Igf signaling, respectively. Furthermore, the regulatory target of Wnts and Igfs, GSK3β, is inefficiently inactivated in male fin regenerates compared with females. Pharmacological inhibition of GSK3 in males increases blastemal proliferation and restores regenerative pattern. Our findings identify a natural sex bias in appendage regenerative capacity and indicate an underlying regulatory circuit in which androgen locally restricts key morphogenetic programs after amputation.


Enhanced production of xylanase from locally isolated fungal strain using agro-industrial residues under solid-state fermentation.
This study is related to the isolation of fungal strain for xylanase production using agro-industrial residues. Forty fungal strains with xylanolytic potential were isolated by using xylan agar plates and quantitatively screened in solid-state fermentation. Of all the tested isolates, the strain showing highest ability to produce xylanase was assigned the code Aspergillus niger LCBT-14. For the enhanced production of the enzyme, five different fermentation media were evaluated. Out of all media, M4 containing wheat bran gave maximum enzyme production. Effect of different variables including incubation time, temperature, pH, carbon and nitrogen sources has been investigated. The optimum enzyme production was obtained after 72 h at 30°C and pH 4. Glucose as a carbon source while ammonium sulphate and yeast extract as nitrogen sources gave maximum xylanase production (946 U/mL/min). This study was successful in producing xylanase by A. niger LCBT-14 economically by utilising cheap indigenous substrate.


Adaptation and psychometric evaluation of the Chinese version of the functional assessment of chronic illness therapy spiritual well-being scale among Chinese childhood cancer patients in China.
Spiritual well-being is a strength for childhood cancer patients to cope with cancer. The availability of a valid and reliable instrument for assessing spiritual well-being is crucial. This study translated and adapted the Functional Assessment of Chronic Illness Therapy Spiritual Well-being scale (FACIT-Sp) for Chinese childhood cancer patients and examined the psychometric properties and factor structure in this population. This was a methodological study. The FACIT-Sp was translated into Chinese. Adaptation was based on our qualitative study. For psychometric evaluation, a convenience sample of 412 were recruited based on the suggested sample size for the exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Childhood cancer patients were included if they aged 8-17 years, with parental consent to participate, able to communicate that they were being treated for cancer, and able to communicate and read Chinese. Participants answered the Chinese version of the adapted FACIT-Sp, the Center for Epidemiology Studies Depression Scale for Children (CES-DC), and the Pediatric Quality of Life Inventory 3.0 Cancer Module (PedsQL). Content validity, convergent validity, internal consistency and test-retest reliability were examined. Both EFA and CFA assessed the structural validity of the adapted FACIT-Sp. The content validity index values for items ranged 0.8-1.0 and that for the scale was 0.84, indicating appropriate content validity. The scale had good internal consistency, with a Cronbach's alpha of 0.815. The FACIT-Sp scores positively correlated with the CES-DC scores, and negatively correlated with PedsQL scores, suggesting that the Chinese version of the adapted FACIT-Sp had reasonable convergent validity. EFA yielded a four-factor (meaning, peace, faith, and connection with others) model. The CFA results revealed that the four-factor model achieved a better fit than the original three-factor model (Chi-Square Mean/Degree of Freedom = 2.240 vs. 3.557, Comparative Fit Index = 0.953 vs. 0.916, Goodness of Fit Index = 0.909 vs. 0.884, Root Mean Square Error of Approximation = 0.078 vs. 0.112). The Chinese version of the adapted FACIT-Sp is a reliable and valid instrument for assessing spiritual well-being among Chinese childhood cancer patients. This instrument can be applied in clinical settings for routine assessment.


A novel multicomponent quadruple/double quadruple domino reaction: highly efficient synthesis of polyheterocyclic architectures.
A novel multicomponent quadruple domino reaction (MCQDR) for the assembly of structurally complex molecular architectures via the formation of three rings and three contiguous stereogenic centers has been accomplished with high regio- and diastereoselectivity. Solvents, catalysts and work-up were not required to obtain the target molecules. In addition, this new protocol is also extended for the multicomponent double quadruple domino reaction (MCDQDR) to create novel polyheterocyclic architectures in an orthogonal manner.


Surgery for low-grade glioma infiltrating the central cerebral region: location as a predictive factor for neurological deficit, epileptological outcome, and quality of life.
A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life. Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution. For the central cohort, the median extent of resection was 92% (range 80%-97%), and for the frontal cohort, the median extent of resection was 93% (range 83%-98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001). Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.


Influencing variables on life satisfaction of Korean elders in institutions.
The number of elders in institutions has increased as family supporting systems have changed in Korea. The purpose of this study were to understand the life satisfaction among elders in institutions and to identify the factors influencing on life satisfaction. The instruments used were Yun(1982)'s scale modified Memorial University of Newfoundland Scale for Happiness(MUNSH) in life satisfaction, ADL and IADL in activity level, Self-rating Depression Scale(SDS) in depression and Norbeck Social Support Questionnaire(NSSQ) scale in social support. Also, Perceived health status was measured by Visual Graphic Rating Scale. The subject of this study is 107 cognitively intact and ambulatory elders in 7 institutions in Daegu city and Kyungpook province. The data have been collected from May 1 to June 30, 2001. For the analysis of collected data, frequency analysis, mean, standard deviation, Pearson's correlation and stepwise multiple regression analysis were used for statistical analysis by SPSSwin(version 9.0) program. Life satisfaction for the elders in institutions showed negative correlation with SDS, and positive correlation with activity level. The regression form of the stepwise multiple regression analysis to investigate the influencing factors of life satisfaction for the elders in institutions was expressed by y = 90.988-0.733x1-0.188x2-0.069x3-0.565x4 (x1: SDS x2: Social support x3: Activity level x4: Monthly pocket Money) and 57.9% of variance in life satisfaction was explained by the model. The factors influencing on life satisfaction among the elders in institutions were SDS, social support, activity level and monthly pocket money. According to the results of this study, depression, social support and activity level are considered the prime causal factors for life satisfaction.


Cardiac electrophysiology of the antiarrhythmic agent recainam (Wy-42,362) in anesthetized dogs: relation to plasma and myocardial concentrations.
The present study was undertaken to characterize the cardiac electrophysiologic effects of the investigational class I antiarrhythmic agent recainam (Wy-42,362) on the canine heart in situ, and to determine the possible relationship between these effects and the concentration of drug in plasma and myocardium. Cardiac conduction times and refractory periods were measured at a paced cycle length of 300 ms in open-chest anesthetized dogs by recording atrial, ventricular, and His bundle electrograms. Recainam was infused intravenously (as a loading + maintenance dose) at either (a) 7.5 mg/kg/20 min + 5 mg/kg/60 min (low-dose group) or (b) 15 mg/kg/20 min + 10 mg/kg/60 min (high-dose group). Samples of plasma and ventricular myocardium were removed at selected times for subsequent analysis. At the end of the maintenance infusion, low-dose recainam produced a plasma concentration of 4.1 +/- 0.5 micrograms/ml and significantly increased atrial conduction time only. Plasma levels with high-dose recainam reached 9.4 +/- 3.5 micrograms/ml at end infusion, and produced significant increases in all measured electrophysiologic parameters except ventricular refractory period. Myocardial levels of recainam were undetectable in the low-dose group, but increased linearly with plasma concentration in the high-dose group with a myocardium/plasma ratio of nearly 1:1. Changes in ventricular conduction time, H-V interval, atrial and ventricular refractory periods, and Wenckebach cycle length correlated significantly with recainam concentration in plasma. In addition, drug levels in the ventricle correlated with the observed changes in both ventricular conduction time and ventricular refractory period. The data suggest that recainam plasma levels may serve as a useful guide in monitoring electrophysiologic response to this agent.


Surgical considerations in ovarian cancer.
A primary consideration for effective management of ovarian cancer is distinguishing patients with advanced bulky disease from those with other stages of disease. It is important to determine whether a tumor is confined to one ovary or is more wide-spread. Surgical management includes removal of both ovaries and tubes, the uterus, omentum, and bulk of the disease. The degree of bulk reduction achieved significantly impacts on survival. Conservation is justified in some cases. Intraperitoneal treatment with platinum-based chemotherapy postsurgery appears to substantially benefit patients with minimal residual disease. In a study comparing two catheter methods, fewer complications were noted with the disposable single-use catheter than with the implanted catheter. Surgical endstaging can definitively identify cured patients. However, it is a difficult procedure and is contraindicated in patients with severe intercurrent illness, previous extensive radiotherapy, and an obliterated peritoneal cavity.


Improving Transplant Medication Safety Through a Technology and Pharmacist Intervention (ISTEP): Protocol for a Cluster Randomized Controlled Trial.
Medication errors, adverse drug events, and nonadherence lead to increased health care utilization and increased risk of adverse clinical outcomes, including graft loss, in solid organ transplant recipients. Veterans living with organ transplants represent a population that is at substantial risk for medication safety events and fragmented care coordination issues. To improve medication safety and long-term clinical outcomes in veteran transplant patients, interventions should address interorganizational system failures and provider-level and patient-level factors. This study aims to measure the clinical and economic effectiveness of a pharmacist-led, technology-enabled intervention, compared with usual care, in veteran organ transplant recipients. This is a 24-month prospective, parallel-arm, cluster-randomized, controlled multicenter study. The pharmacist-led intervention uses an innovative dashboard system to improve medication safety and health outcomes, compared with usual posttransplant care. Pharmacists at 10 study sites will be consented into this study before undergoing randomization, and 5 sites will then be randomized to each study arm. Approximately, 1600 veteran transplant patients will be included in the assessment of the primary outcome across the 10 sites. This study is ongoing. Institutional review board approval was received in October 2018 and the study opened in March 2019. To date there are no findings from this study, as the delivery of the intervention is scheduled to occur over a 24-month period. The first results are expected to be submitted for publication in August 2021. With this report, we describe the study design, methods, and outcome measures that will be used in this ongoing clinical trial. Successful completion of the Improving Transplant Medication Safety through a Technology and Pharmacist Intervention study will provide empirical evidence of the effectiveness of a feasible and scalable technology-enabled intervention on improving medication safety and costs. ClinicalTrials.gov NCT03860818; https://clinicaltrials.gov/ct2/show/NCT03860818. PRR1-10.2196/13821.


Time of day differences in neural reward responsiveness in children.
The Reward Positivity (∆RewP) event-related potential (ERP), generally quantified as the difference between neural responsiveness to monetary gains (RewP-Gain) and losses (RewP-Loss) is commonly used as an index of neural reward responsiveness. Despite the popularity of this ERP component in studies of reward processing, knowledge about the role of state-related influences on the ∆RewP is limited. The present study examined whether ∆RewP amplitudes may differ based on when during the day they are assessed and whether age or sex would moderate this link. Participants were 188 children between the ages of 7 and 11 (47.3% female) without a lifetime history of a major depressive disorder or any anxiety disorder recruited from the community. Children completed the Doors task during which continuous electroencephalography was recorded to isolate the ∆RewP. To better isolate this ERP component from other temporally or spatially overlapping ERPs, we used temporospatial principal component analysis. We found that time of day (ToD) differences in the ∆RewP amplitude varied based on children's age. Specifically, older, compared to younger, children exhibited stronger responses to gains versus losses between 11:15 a.m. and 12:30 p.m. and after around 5:15 p.m. Further, these age-related differences appeared to be driven specifically by older children's reduced neural responsiveness to losses. The findings have methodological implications by highlighting the importance of accounting for the ToD at which ∆RewP-focused study sessions are conducted as well as for demographic characteristics of the participants, such as their age.


Impact of Race and Ethnicity on Outcomes for Children Waitlisted for Pediatric Liver Transplantation.
African Americans and other minorities are known to face barriers to health care influencing their access to organ transplantation but it is not known whether these barriers exist among pediatric liver transplant waitlist candidates. We sought to determine whether outcomes on the waitlist (ie, mortality, deceased donor liver transplantation [DDLT], and living-donor liver transplantation [LDLT]) varied by race/ethnicity. National registry data were studied to estimate the race/ethnicity-specific risk of waitlist mortality, DDLT and LDLT in children (<18 years) waitlisted between March 2002 and March 2015. There was no evidence of racial/ethnic disparities in waitlist mortality. Compared to Caucasians, LDLT varied by race/ethnicity, with only 6.7% African Americans and 10.3% Hispanic children receiving LDLT compared with 12.4% Caucasian, 13.3% Asian, and 9.4% mix/other children. In an adjusted Cox proportional hazards model, African Americans were half as likely as Caucasians to use LDLT (hazard ratio [HR]: 0.410.550.73) but had similar use of DDLT (HR: 0.981.061.16). In a model that considered mortality, DDLT, and LDLT as competing risks, African Americans had significantly reduced incidence of LDLT (subhazard ratio [sHR]: 0.410.560.75) compared to Caucasians, but increased use of DDLT (sHR: 1.061.161.26). Compared to Caucasian children, African-American children are less likely to use LDLT but have higher rates of DDLT and similar survival on the waitlist. Additional research is necessary to understand the clinical and socioeconomic factors contributing to lower utilization of LDLT among African-American children awaiting transplantation.


Into the fire: Investigating the introduction of cremation to Nordic Bronze Age Denmark: A comparative study between different regions applying strontium isotope analyses and archaeological methods.
Changes in funerary practices are key to the understanding of social transformations of past societies. Over the course of the Nordic Bronze Age, funerary practices changed from inhumation to cremation. The aim of this study is to shed light on this fundamental change through a cross-examination of archaeometric provenance data and archaeological discussions of the context and layouts of early cremation graves. To this end, we conducted 19 new provenance analyses of strontium isotopes from Early Nordic Bronze age contexts in Thisted County and Zealand and Late Bronze Age contexts from Thisted County and Vesthimmerland (Denmark). These data are subsequently compared with data from other extant relevant studies, including those from Late Bronze Age Fraugde on the Danish island of Fyn. Overall, the variations within our provenience data suggest that the integration and establishment of cremation may not have had a one-to-one relationship with in-migration to Nordic Bronze Age Denmark. Moreover, there seems to be no single blanket scenario which dictated the uptake of cremation as a practice within this part of Southern Scandinavia. By addressing habitus in relation to the deposition of cremations as juxtaposed with these provenance data¸ we hypothesize several potential pathways for the uptake of cremation as a new cultural practice within the Danish Nordic Bronze Age and suggest that this may have been a highly individual process, whose tempo may have been dictated by the specificities of the region(s) concerned.


Pancreatic insulin release and peripheral tissue resistance in Zucker obese rats fed high- and low-carbohydrate diets.
An effort was made to determine to what degree the hyperinsulinemia found in the genetically obese Zucker rat is the result of the carbohydrate content of the diet. When Zucker obese rats are fed precisely the same amount of carbohydrate as lean controls and allowed to become obese by drinking vegetable oil, their pancreatic islets still release 59% more insulin than do those from lean controls. When their diet contains even more carbohydrate, fed from weaning, and they become equivalently obese, their islet insulin release is increased by an additional 46%. An obese Zucker rat fed a high-carbohydrate diet possesses muscle sensitivity to insulin and enlarged adipocytes undergoing active lipogenesis. A rat becoming equivalently obese on a high-fat diet has an absence of insulin sensitivity in muscle and diminished lipogenesis in adipocytes. Clearly, the composition of the diet plays an important role in the metabolic consequences of obesity, but neither diet nor changes in peripheral glucose metabolism can completely explain the hyperinsulinemia.


Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor.
Feline infectious peritonitis (FIP) is a highly fatal disease caused by a virulent feline coronavirus in domestic and wild cats. We have previously reported the synthesis of potent coronavirus 3C-like protease (3CLpro) inhibitors and the efficacy of a protease inhibitor, GC376, in client-owned cats with FIP. In this study, we studied the effect of the amino acid changes in 3CLpro of feline coronavirus from a feline patient who received antiviral treatment for prolonged duration. We generated recombinant 3CLpro containing the identified amino acid changes (N25S, A252S or K260 N) and determined their susceptibility to protease inhibitors in the fluorescence resonance energy transfer assay. The assay showed that N25S in 3CLpro confers a small change (up to 1.68-fold increase in the 50% inhibitory concentration) in susceptibility to GC376, but other amino acid changes do not affect susceptibility. Modelling of 3CLpro carrying the amino acid changes was conducted to probe the structural basis for these findings. The results of this study may explain the observed absence of clinical resistance to the long-term antiviral treatment in the patients.


Natural History of Afferent Baroreflex Failure in Adults.
To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester. We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests). A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period. ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.


Potential Neuroprotective Effect of miR-451 Against Cerebral Ischemia/Reperfusion Injury in Stroke Patients and a Mouse Model.
Recently, microRNAs (miRs) have been reported to be novel regulators in ischemic stroke. In this study, we investigated the pattern of miR-451 expression along with its clinical application in human ischemic stroke and in an in vivo mouse model. The level of miR-451 was evaluated in patients and mice after ischemic stroke. National Institute of Health Stroke Scale scores and brain infarct volume were analyzed to the correlation of miR-451 expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion model consisting of 12 adult male mice at 24 hours after the middle cerebral artery occlusion. The results showed that miR-451 levels in the circulating blood of ischemic stroke patients were greatly decreased compared with the control. Further correlation analysis revealed a negative association between miR-451 and National Institute of Health Stroke Scale scores (r = -0.6104, P < 0.001) and infarct volume (r = -0.5442, P < 0.001). Moreover, miR-451 was down-regulated in response to middle cerebral artery occlusion in vivo, along with a negative correlation between miR-451 in brain and blood (r = 0.9240, P < 0.01). In addition, forced expression of miR-451 weakened ischemic brain infarction and apoptosis levels in focal ischemia-stroked mice, while downregulation of miR-451 significantly augmented ischemic injury. In conclusion, miR-451 displays the neuroprotective effect in ischemic stroke and might serve as a novel therapeutic target of ischemic stroke.


Aptamer-functionalized polydiacetylene biosensor for the detection of three foodborne pathogens.
Rapid, simple and sensitive screening of foodborne pathogens is of great significance to ensure food safety. In this study, an aptamer-functionalized polydiacetylene (Apta-PDA) biosensor was developed for the detection of E. coli O157:H7, S. typhimurium or V. parahaemolyticus. First, aptamers responding to the target bacteria were modified on the surface of magnetic beads by covalent binding to form MBs-oligonucleotide conjugates for bacterial enrichment. Then, an Apta-PDA biosensor was obtained by connecting the aptamers to the PDA nanovesicles using the carbodiimide method. Molecular recognition occurred in the presence of the target bacteria, whereby the aptamer folded into a sequence-defined unique structure, resulting in an MBs-Apta/bacteria/Apta-PDA sandwich structure. Due to the optical properties of PDA, the blue-red transition of the detection system could be observed by the naked eye and quantified by the colorimetric response percentage (CR%). Under optimized conditions, the detection limits of E. coli O157:H7, S. typhimurium and V. parahaemolyticus were 39, 60 and 60 CFU/ml, respectively, with a selectivity of 100% and a reaction time of 30 min. Compared with the gold standard method, the accuracy of the three target bacteria detection reached 98%, 97.5% and 97%, respectively, and the sensitivity and specificity were both greater than 90%. The entire detection process was rapid and easy to execute without any special equipment, making this technology particularly suitable for resource-poor laboratories or regions.


Global proteogenomic analysis of human MHC class I-associated peptides derived from non-canonical reading frames.
In view of recent reports documenting pervasive translation outside of canonical protein-coding sequences, we wished to determine the proportion of major histocompatibility complex (MHC) class I-associated peptides (MAPs) derived from non-canonical reading frames. Here we perform proteogenomic analyses of MAPs eluted from human B cells using high-throughput mass spectrometry to probe the six-frame translation of the B-cell transcriptome. We report that ∼ 10% of MAPs originate from allegedly noncoding genomic sequences or exonic out-of-frame translation. The biogenesis and properties of these 'cryptic MAPs' differ from those of conventional MAPs. Cryptic MAPs come from very short proteins with atypical C termini, and are coded by transcripts bearing long 3'UTRs enriched in destabilizing elements. Relative to conventional MAPs, cryptic MAPs display different MHC class I-binding preferences and harbour more genomic polymorphisms, some of which are immunogenic. Cryptic MAPs increase the complexity of the MAP repertoire and enhance the scope of CD8 T-cell immunosurveillance.


How bulk fluid renewal can affect in vitro drug release from PLGA implants: Importance of the experimental set-up.
The aim of this study was to better understand the potential impact of partial vs. complete renewal of the bulk fluid during drug release measurements from poly (lactic-co-glycolic acid) (PLGA)-based implants. A "standard experimental set-up", in which the implants were directly exposed to well agitated phosphate buffer pH 7.4 was used, as well as set-ups, in which the implants were embedded within agarose hydrogels (mimicking living tissue). The gels were exposed to well agitated phosphate buffer pH 7.4. Ibuprofen-loaded implants were prepared by hot melt extrusion. The systems were thoroughly characterized before and during drug release by optical and scanning electron microscopy, gravimetric analysis, pH and solubility measurements as well as gel permeation chromatography. The bulk fluid was either completely or partially replaced by fresh medium at each sampling time point. In all cases, sink conditions were provided in the agitated bulk fluids throughout the experiments. Interestingly, the agarose set-ups did not show any noteworthy impact of the bulk fluid sampling volume on the observed drug release patterns, whereas complete fluid renewal in the "standard set-up" led to accelerated drug release. This could be explained by the considerable fragility of the implants once substantial polymer swelling set on, transforming them into PLGA gels: Complete fluid renewal caused partial disintegration and damage of the highly swollen systems, decreasing the lengths of the diffusion pathways for the drug. The mechanical stress is very much reduced at low sampling volumes, or if the implants are embedded within agarose gels. Thus, great care must be taken when defining the conditions for in vitro drug release measurements from PLGA-based implants: Once substantial system swelling sets on, the devices become highly fragile.


Fetal Membrane Inflammation Induces Preterm Birth Via Toll-Like Receptor 2 in Mice With Chronic Gingivitis.
Inflammation is associated with preterm birth. We previously described a mouse model of chronic inflammation-induced preterm birth after dental Porphyromonas gingivalis infection. The aim of this study was to employ this model system to investigate the mechanisms through which enhanced uterine contractility induces preterm birth. Messenger RNA (mRNA) encoding contraction-associated proteins, such as oxytocin receptors, was measured at various gestational time points by real-time polymerase chain reaction (PCR). Spontaneous and oxytocin-induced uterine contractile activity at gestational day 18 was assessed using a tissue organ bath. The expression levels of Toll-like receptor 2 (TLR2), TLR4, cyclooxygenase (COX)-2, nuclear factor-kappa B (NF-κB) p65, and p38 mitogen-activated protein kinase (MAPK) on gestational day 18 were also determined by real-time PCR or Western blotting. Messenger RNA encoding contraction-associated proteins was increased at gestational day 18, and the spontaneous contractile activity (1.6-fold greater area under the contraction curve) and sensitivity to oxytocin (EC50: 8.8 nM vs 2.2 nM) were enhanced in the P gingivalis group compared to those in the control group. In the P gingivalis group, COX-2 mRNA expression was not elevated in the placenta or myometrium but was upregulated 2.3-fold in the fetal membrane. The TLR2 mRNA levels in the fetal membrane were 2.7-fold higher in the P gingivalis group, whereas TLR4 levels were not elevated. Activation of the NF-κB p65 and p38 MAPK pathways was enhanced in the fetal membrane of the P gingivalis group. Thus, in mice with chronic dental P gingivalis infection, TLR2-induced inflammation in the fetal membrane leads to upregulation of uterine contractility, leading to preterm birth.


Identification of a single p19 gene and three p40 paralogues in grass carp (Ctenopharyngodon idellus): Their potential for the formation of interleukin 23 and inducible expression in vitro and in vivo.
Interleukin (IL-) 23, a member of IL-12 family, is a composite cytokine with the subunits of p19 and p40. Although IL-12 and IL-23 share the p40 subunit, they play vastly different roles in immune regulation. In teleost, much emphasis has been placed on the identification of IL-12, but evidence for the existence of IL-23 is still lacking. In the present study, a p19 gene and three p40 paralogues were isolated and identified from grass carp, suggesting multiple assembly of IL-23 molecules in fish species. To address this issue, the existence of different p19/p40 heterodimers were examined by Co-Immunoprecipitation (Co-IP) assay, showing that only co-expression of p19 and each p40 subunit could produce the soluble proteins corresponding to three IL-23 isoforms. Additionally, bacterial infection could up-regulate the mRNA expression of p19, p40a and p40b but not p40c in head kidney, indicating distinct expression patterns of three p40 paralogues. Moreover, in vitro experiments demonstrated that both B-cell stimulator, LPS and T-cell mitogen, PHA markedly increased the mRNA levels of p19 and three p40 paralogues in grass carp periphery blood lymphocytes (PBLs). The simultaneous up-regulation of mRNA expression of p19 and p40 paralogues in response to immune stimuli supports the idea that p19 may form heterodimeric molecules with three p40 subunits in grass carp under immune activation. These findings for the first time highlight the potential of p19 and p40 for dimerization in fish, particularly the existence of three IL-23 isoforms as soluble heterodimeric cytokines in grass carp, thereby providing the basis for further investigating the function of IL-23 in fish immunity.


Relationships between some psychological assessments, body-build, and physiological stress responses.
A number of physiological responses to the psychological stress of an oral academic examination were observed, including heart rate, respiration rate, blood pressure, urinary 17-oxogenic steroid excretion, and plasma corticosteroid concentration. The results were related to body-build and to four psychological tests: Eysenck Personality Inventory, Taylor Manifest Anxiety Scale, IPAT Anxiety Scale, and Stimulus-Response Inventory. No significant associations were found between the psychological test results and anticipatory physiological activity just before the examination began, including excretion of 17-oxogenic steroids. Respiration rate was not increased by anticipatory stress, unlike the other variables, which were significantly higher than control values taken under resting conditions three months later. The students of primarily linear physique had significantly higher plasma corticosteroid values than the predominantly muscular subjects at the time of the examination, as found previously. They also had significantly higher analogue measures of the degree of anxiety experienced at the examination (assessed both by the subject and by an observer). Therefore, linear subjects appear to experience more anxiety than muscular students in a similar situation of psychological stress. Both the IPAT Scale and S-R Inventory results were significantly higher for the linear group but there were no significant differences for the EPI and TMAS scores, as used in previous studies. The importance of constitutional factors associated with body-build in relation to at least some aspects of personality is strongly suggested by the findings.


Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells.
Glioblastoma (GBM) is a high-grade glioma with a complex microenvironment, including various inflammatory cells and mast cells (MCs) as one of them. Previously we had identified glioma grade-dependent MC recruitment. In the present study we investigated the role of plasminogen activator inhibitor 1 (PAI-1) in MC recruitment.PAI-1, a primary regulator in the fibrinolytic cascade is capable of forming a complex with fibrinolytic system proteins together with low-density lipoprotein receptor-related protein 1 (LRP1). We found that neutralizing PAI-1 attenuated infiltration of MCs. To address the potential implication of LRP1 in this process, we used a LRP1 antagonist, receptor-associated protein (RAP), and demonstrated the attenuation of MC migration. Moreover, a positive correlation between the number of MCs and the level of PAI-1 in a large cohort of human glioma samples was observed. Our study demonstrated the expression of LRP1 in human MC line LAD2 and in MCs in human high-grade glioma. The activation of potential PAI-1/LRP1 axis with purified PAI-1 promoted increased phosphorylation of STAT3 and subsequently exocytosis in MCs.These findings indicate the influence of the PAI-1/LRP1 axis on the recruitment of MCs in glioma. The connection between high-grade glioma and MC infiltration could contribute to patient tailored therapy and improve patient stratification in future therapeutic trials.


Total parenteral nutrition. A review.
Surgery, trauma, severe sepsis and burns are the most demanding physical stresses that a patient is likely to suffer, yet until recently, the nutrition of these patients was usually completely ignored. The concept of adequate feeding by the intravenous route is now well accepted and the authors present a review of many of the appropriate preparations which are available in South Africa, as well as a description of several regimens that have been successful in total parenteral nutrition (TPN).


[Age-related dynamics of the genetic marker distribution in an irradiated population. Haptoglobin genetic system].
The age dynamics of haptoglobin (Hp) type and allele distribution was studied in 985 workers aged 35-79 years who worked in the atomic industry. These workers were exposed to chronic radiation in a wide range of doses 17-40 years ago. Along with the chi 2 test, the relative and attributive risks of elimination of Hp types and alleles were determined to obtain the qualitative characteristics of age alterations. The substantial changes in distribution of Hp types and alleles were revealed in individuals older than 60 years. These changes depended on doses of external and internal irradiation. For instance, in individuals of this age group, who received the total dose of gamma-radiation (less than 100 cGy) and or that of plutonium-239 incorporation (less than 1.48 kBq), a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 was observed. However, among the individuals of similar age (older than 62 years), who received a higher total dose of external and/or internal radiation, the different Hp type distribution showed a decrease in Hp 2-1 and an increase in Hp 1-1. In the latter case, the changes with age were dose-dependent. In individuals over 60 years of age with essential hypertension or diabetes mellitus and those who had a myocardial infarction, a decrease in Hp 2-2 and Hp2 and an increase in Hp 1-1 and Hp1 were found. This explains the changes with age in individuals irradiated at lower doses. The peculiar changes with age in individuals irradiated at higher doses are possibly due to the difference in morbidity and mortality from malignancy in various Hp type carriers.


[Ecological risk assessment and its application].
Ecological risk assessment, closely linked to environmental toxicology, is becoming one of the most widely expanding disciplines in environmental science. A number of frameworks for ecological risk assessment have been developed by the USEPA, Environment Canada and European Commission in recent years. This review described the common elements, the process and steps of ecological risk assessment. In addition to drawing upon the recent published literature, we have developed some examples of applications based on our collective experiences in conducting ecological risk assessments.


Neurocytoma arising in an adrenal gland mature teratoma.
Mature teratoma of adrenal gland is a rare entity. Neurocytoma is a low grade neuronal tumor even rarely seen among central nervous system tumors. Nervous system tumors arising in teratomas are frequently originated from glial or primitive neuroectodermal cells. Here we report a neurocytoma arising in mature cystic teratoma in the right adrenal gland of an 8 years old boy. Histological examination revealed a tumor composed of solid sheets in fibrillar basis with small uniform cells in the neuroglial tissue in teratoma. This is only the second case demonstrating a neurocytoma arising in a mature cystic teratoma in the literature.


Hiatal mesh repair--current status.
Most surgeons believe that cruroplasty (hiatoplasty) is an essential part of antireflux operations. One of the main causes of failure after antireflux operation is gastric (wrap) herniation through the hiatus that may be attributed to breakdown of the hiatal closure or a faulty repair. Surgeons are at present faced with the dilemma of choosing between a risk of recurrence and the fear of complications of prosthetic hiatal reinforcement. We reviewed the literature to evaluate the current status of hiatal mesh repair (HMR). Indication, technique, complications, and results are shown. Available data show a small number of mesh-related complications compared with the number of patients submitted to the procedure, and better results of HMR compared with simple hiatal closure. We support the use of HMR when performed by skilled foregut surgeons, as complications described occurred more frequently in the earliest cases of the series. In addition, HMR should be probably used selectively. However, studies to identify the patients at risk of hernia recurrence or mesh-related complications are still elusive. The ideal type of mesh and the ideal technique for mesh implantation are yet to be established.


[Coronary collateral circulation in infarction-related artery in patients with acute myocardial infarction with rise and without rise of ST segment].
The authors analyzed a condition of coronary collateral circulation in infarction-related artery in patients with acute myocardial infarction with rise and without rise of ST segment. The assessment of collateral circulation was made by coronary angiography using Rentop scale. Results of the research showed, that collateral circulation wasn't visualized by angiography in the first hours after acute myocardial infarction with the rise of ST segment. Apparently, this circulation didn't significantly assisted in maintenance of vital capacity of the myocardium in the pool of infarction-related occlusive coronary artery. Visualization of collateral circulation was noted in majority of patients with acute myocardial infarction without the rise of ST segment. Collateral flow was an important alternative source of blood supply of the heart in patients without rise of ST segment in the period of critical reduction of the antegrade blood flow.


Autoimmune hypophysitis: a single centre experience.
Autoimmune hypophysitis (AH) is a rare primary autoimmune inflammatory disorder involving the pituitary gland. A retrospective analysis of the clinical features and outcome of patients diagnosed with AH between 1988 and 2006, was carried out. 15 patients (14 females and one male) with AH were identified. Three patients presented in the peripartum period. Headache, vomiting and visual field defects, suggestive of an expanding sellar mass, were the most common presenting symptoms (67 percent). The most common deficient hormone was adrenocorticotropic hormone (ACTH) (67 percent), followed by thyroid stimulating hormone (53 percent) and gonadotropins (40 percent). Imaging revealed a definite, enhancing sellar mass in 87 percent of the patients and stalk thickening in 33 percent of the patients. Three patients underwent surgery. On serial monitoring, the sellar mass regressed or disappeared spontaneously without any immunosuppressive treatment in the other ten patients with a definite sellar mass. We report a higher female to male ratio and a lower incidence of peripartum cases in our series. Symptoms of mass effect were the most common presentation, while ACTH was the most commonly-deficient hormone. Surgery was rarely needed, and most patients experienced a spontaneous resolution of the mass.