Distribution of perfluoroalkyl substances (PFASs) in aquatic plant-based systems: From soil adsorption and plant uptake to effects on microbial community.
This study systematically explored the distribution of perfluoroalkyl substances (PFASs) through soil adsorption and plant bioaccumulation in aquatic plant-based systems, derived from a surface flow constructed wetland (CW) planted with Typha angustifolia. The water-soil-plant systems were fortified with eight perfluoroalkyl subsntances (PFASs) at different concentrations. The potential for individual PFAS adsorption onto soil substrate and bioaccumulation in the plants increased with the increasing PFAS initial concentrations. Longer-chain PFASs exhibited higher affinity to soil substrate compared to shorter-chain PFASs. The highest concentration in the soil was observed for PFOS (51.3 ng g-1), followed by PFHxS (9.39 ng g-1), and PFOA (5.53 ng g-1) at low PFAS level. The perfluoroalkyl chain length dependent trend was also seen in the roots with the highest individual PFAS concentration for PFOS (68.9 ng g-1), followed by PFOA (18.5 ng g-1) and PFHxS (13.4 ng g-1). By contrast, shorter-chain PFASs were preferentially translocated from roots to shoots in Typha angustifolia. A significant (p < 0.05) positive correlation between bioaccumulation factor (BAFplant/water) (whole plant) and perfluoroalkyl chain length was observed. PFASs content in the plant compartments increased with increasing PFAS concentrations in the soil. Mass balance analysis indicates that approximately 40.7-99.6% of PFAS mass added to the system was adsorbed onto the soil and bioaccumulated in the plant tissues of T. angustifolia. Soil adsorption played a vital role in PFAS mass distribution. The results of Illumina high-throughput sequencing show that the bacterial diversity decreased upon PFAS exposure. The most predominant phyla retrieved were Proteobacteria (24.7-39.3%), followed by Actinobacteria (4.2-41.1%), Verrucomicrobia (7.9-25.1%), Bacteroidetes (10.2-20.4%), Cyanobacteria (0.4-16.5%), and Firmicutes (1.1-6.4%). The PFAS enrichment caused the changes (p > 0.05) in the structure and composition of bacterial community. This study helps to gain insight into a better understanding of the potential for PFASs distribution in an aquatic plant-based system and the impact on dynamic of microbial community exposed to PFASs.


Design, synthesis and biological evaluation of new dihydropyridine derivatives as PD-L1 degraders for enhancing antitumor immunity.
Immune checkpoint blockade (ICB) by targeting programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1) signaling pathway is a promising strategy for tumor immunotherapy. Developing small-molecules inducing PD-L1 protein degradation has been proven as an alternative and useful approach for targeting the immunotherapy pathway. Our previous study showed that Lercanidipine could down-regulate the expression of PD-L1 protein, but its calcium influx antagonistic activity hampers further development. For attenuating the unexpected calcium channel blockade effect, a series of compounds were synthesized and evaluated through structure-activity relationship (SAR) exploration. Amongst, compound F4 exhibited a loss of calcium antagonistic activity, while the PD-L1 degradation activity can still retain. Further studies indicated that F4 degraded PD-L1 dose- and time-dependently, and may function through a lysosomal-dependent manner. Furthermore, compound F4 showed a good bioavailability value of 24.9% in mice. Moreover, the F4-induced PD-L1 degradation strengthened the T cell-mediated killing of tumor cells. Our findings show the discovery of a new PD-L1 degrader, providing a potential strategy for immunotherapy.


Induction of metallothionein by exposure to normobaric 100% oxygen atmosphere in rats with different zinc supply.
The objective of this study was to determine the effects of an oxygen enriched environment on the induction of the metalloprotein metallothionein (MT) and its relation to zinc metabolism in rats supplied with different levels of dietary zinc. Male albino rats were fed purified diets based on maize starch, egg white, saccharose and soybean oil differing in the concentration of zinc (1; 20; 100; 500 mg Zn/kg diet). At a dietary zinc supply of 1 mg/kg, the rats developed a zinc deficiency indicated by visual and biochemical parameters. At the end of the 37-day feeding period, half of the rats were exposed to 100% oxygen for 12 h. The oxygen treatment significantly reduced plasma zinc in the zinc supplemented rats and reduced it in tendency in the zinc deficient rats. The MT concentration was increased in the zinc supplemented groups in the liver, kidney and lung. The oxygen treatment elevated the metallothionein concentration in the two high zinc supplemented groups (100 and 500 mg Zn/kg diet) in the liver. The response of the zinc concentration in plasma and of hepatic metallothionein levels to oxygen exposure indicates a role of metallothionein in zinc distribution or interactions with other trace elements to support antioxidant capacity, rather than an impact on direct scavenging activity of free radicals.


A multicenter prospective study validated a nomogram to predict individual risk of dependence in ambulation after rehabilitation.
To develop the Functional Risk Index for Dependence in Ambulation (FRIDA) score, a nomogram to predict individual risk of dependence in ambulation at discharge from postacute rehabilitation and validate its performance temporally and spatially. We analyzed the database of a multicenter prospective observational quality cohort study conducted from January 2012 to March 2016, including data from 8,796 consecutive inpatients who underwent rehabilitation after stroke, hip fracture, lower limb joint replacement, debility, and other neurologic, orthopedic, or miscellaneous conditions. A total of 3,026 patients (34.4%) were discharged dependent in ambulation. In the training set of 5,162 patients (58.7%), Lasso-regression selected advanced age, premorbid disability, and eight indicators of medical and functional adverse syndromes at baseline to establish the FRIDA score. At the temporal validation obtained on an external set of 3,234 patients (41.3%), meta-analyses showed that the FRIDA score had good and homogeneous discrimination (summary area under the curve 0.841, 95% confidence interval = 0.826-0.855, I2 = 0.00%) combined with accurate calibration (summary Log O/E ratio 0.017, 95% confidence interval -0.155 to 0.190). These performances remained stable at spatial validation obtained on 3,626 patients, with substantial heterogeneity of estimates across nine facilities. Decision curve analyses showed that a FRIDA score-supported strategy far outperformed the usual "treat all" approach in each impairment categories. The FRIDA score is a new clinically useful tool to predict an individual risk for dependence in ambulation at rehabilitation discharge in many different disabilities, and may also reflect well the case-mix composition of the rehabilitation facilities.


Development of a quantitative polymerase chain reaction method using a live bacterium as internal control for the detection of Listeria monocytogenes.
A novel real-time quantitative polymerase chain reaction (Q-PCR) assay was developed for rapid and accurate detection of Listeria monocytogenes. In this Q-PCR assay, a computational DNA random shuffling method was used to design an internal amplification control (IAC) sequence, which was the same in length and G + C content to the hly amplicon. This IAC sequence was inserted into the genome of L. monocytogenes to create a mutant strain named L. monocytogenes-IAC. The LM-IAC was used as an internal control during the PCR assay and produced accurate quantification of L. monocytogenes due to similar DNA extraction and amplification efficiencies between LM-IAC strain and wild-type L. monocytogenes. Quantification by this method was over a 5-log linearity range of initial L. monocytogenes with an R(2) value of 0.9997. This PCR method will provide accurate quantification of L. monocytogenes and can be used in the clinic and food assays for diagnostic purposes.


Expression profiling of tumor necrosis factor alpha-induced apoptosis-associated genes in human solid tumor cell lines.
The induction of genes associated with cellular apoptosis by tumor necrosis factor-alpha (TNF-alpha) in human cancer cell line sof various tissue origins may characterize TNF-alpha responder cell lines/cancers. Using quantitative real-time polymerase chain reaction (PCR), the comprehensive molecular profiling of genes downstream of the TNF-alpha receptor genes in 91 well-defined human cancer cell lines allowed us to elucidate relationships between TNF-alpha response and the genetic expression profiles of the target cell lines. Among the 52 genes tested, the above average expression of Akt mRNA showed significant correlation with TNF-alpha-induced susceptibility to apoptosis. In addition, multidrug resistance protein 5 (MRP5) and tumor necrosis factor receptor type 1 (TNFR1) mRNA expressions also appear to be possible markers for responsiveness to TNF-alpha. These results provide a preliminary basis for the screening for genetic markers that may help to predict a favorable therapeutic outcome, and also to identify patients who may benefit from cytokine therapy.


[Angiomatosis of the colon; presentation of one case and review of the literature (author's transl)].
Following a brief introduction in which they outline the frequency of colonic angiomatosis and its characteristic symptom triad, the authors describe one case of this condition come to their observation and treated surgically. Next they discuss the classification, differential diagnosis versus other colonic diseases and disorders, available diagnostic aids, and therapeutic resources. They stress in particular the difficulty of diagnosing this condition correctly, to the point where definite recognition is often made only by exploratory laparotomy.


The mechanical complications of colostomy in infants and children: analysis of 473 cases of a single center.
The purpose of this study was to determine the morbidity, mortality and possible risk factors in children who underwent colostomy. A total of 473 children who underwent colostomy in our clinic between 1983 and 2005 were retrospectively reviewed. Of these patients, 278 were boys and 195 were girls. The major indications for colostomy were anorectal malformation (252 patients), Hirschsprung's disease (117), and trauma (66). The patients' age ranged from 1 day to 15 years. Of the 473 patients, 254 (53.6%) were < 1 month of age, 97 (20.5%) were 1-12 months of age, and 122 (25.7%) were > 12 months of age. The side of colostomy was transverse in 341 (72%) patients and sigmoid in 132 (28%). The type of colostomy was loop in 364 (77%) patients and diverting in 109 (23%). Postoperative complication was observed in 80.5% of patients; excoriation (46.5%), prolapse (20.5%), stomal obstruction/stenosis (6.1%), and stomal bleeding (2.1%). A stomal revision was required for 26 (5.5%) patients. Overall, 50 (10.5%) patients died; 37 were related directly to major congenital anomalies, while 13 (2.7%) patients had a colostomy complication. The age of patients who died was < 1 month in 46 (92%) patients. The incidence of morbidity and mortality in children with colostomy is significantly high, particularly in neonates. Prompt colostomy procedure by an experienced hand, prompt stomal care under the supervision of a trained and experienced stomal care giver and early closure of the colostomy may increase the survival of these patients.


A morphological methodology for three-dimensional human face soft-tissue landmarks extraction: a preliminary study.
Assessment of facial soft tissues could be implemented using only anatomical landmarks. These points are so significant in the medical context because are able to provide significant information about the human face morphology and dimensions. At present their detection and location is made by expert physicians using palpation. Even if this procedure normally provides reliable information, the reliability of the results is proportional to the expertise of the physician. Considering that at present many physicians are beginning to use 3D scanners that provide three-dimensional data of the human face, it is possible to implement a robust and repeatable methodology that supports the physician's diagnosis. To reach this goal it is necessary to implement a methodology based on geometrical codification of landmarks and which mathematically formalizes the physician's visual and palpation analyses of the real patient.


The cannabinoid agonist CB-13 produces peripherally mediated analgesia in mice but elicits tolerance and signs of central nervous system activity with repeated dosing.
Activation of cannabinoid receptor type 1 (CB 1 ) produces analgesia in a variety of preclinical models of pain; however, engagement of central CB 1 receptors is accompanied by unwanted side effects, such as psychoactivity, tolerance, and dependence. Therefore, some efforts to develop novel analgesics have focused on targeting peripheral CB 1 receptors to circumvent central CB 1 -related side effects. In the present study, we evaluated the effects of acute and repeated dosing with the peripherally selective CB 1 -preferring agonist CB-13 on nociception and central CB 1 -related phenotypes in a model of inflammatory pain in mice. We also evaluated cellular mechanisms underlying CB-13-induced antinociception in vitro using cultured mouse dorsal root ganglion neurons. CB-13 reduced inflammation-induced mechanical allodynia in male and female mice in a peripheral CB 1 -receptor-dependent manner and relieved inflammatory thermal hyperalgesia. In cultured mouse dorsal root ganglion neurons, CB-13 reduced TRPV1 sensitization and neuronal hyperexcitability induced by the inflammatory mediator prostaglandin E 2 , providing potential mechanistic explanations for the analgesic actions of peripheral CB 1 receptor activation. With acute dosing, phenotypes associated with central CB 1 receptor activation occurred only at a dose of CB-13 approximately 10-fold the ED 50 for reducing allodynia. Strikingly, repeated dosing resulted in both analgesic tolerance and CB 1 receptor dependence, even at a dose that did not produce central CB 1 -receptor-mediated phenotypes on acute dosing. This suggests that repeated CB-13 dosing leads to increased CNS exposure and unwanted engagement of central CB 1 receptors. Thus, caution is warranted regarding therapeutic use of CB-13 with the goal of avoiding CNS side effects. Nonetheless, the clear analgesic effect of acute peripheral CB 1 receptor activation suggests that peripherally restricted cannabinoids are a viable target for novel analgesic development.


Transobturator tape procedure versus tension-free vaginal tape for treatment of stress urinary incontinence.
To compare the efficacy and safety of the tension-free vaginal tape (TVT) and inside-out transobturator tape (TVT-O) procedures for the treatment of stress urinary incontinence (SUI). A total of 315 women with or without concomitant pelvic organ prolapse repairs were randomly allocated to undergo a TVT or TVT-O procedure. Demographic data, intra- and postoperative complications, and surgical outcomes were analyzed. Fifteen patients were lost to follow-up. There were no significant differences in cure rates between the 2 groups at 6, 12, 24, and 36 months' follow-up. Hematomas occurred in 4 patients and there were 6 vaginal tape erosions. Urinary retention and de novo urinary urgency were similar in both groups. The operative time was significantly shorter for TVT-O than for TVT without other procedures (P<0.001) and postoperative groin/thigh pain was higher (P<0.05) in the TVT-O group. Both techniques appear equally effective for the treatment of SUI. However, TVT-O had a shorter operative time and a higher rate of groin/thigh pain.


The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.
Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application.


Origin and population history of a recent colonizer, the yellow warbler in Galápagos and Cocos Islands.
The faunas associated with oceanic islands provide exceptional examples with which to examine the dispersal abilities of different taxa and test the relative contribution of selective and neutral processes in evolution. We examine the patterns of recent differentiation and the relative roles of gene flow and selection in genetic and morphological variation in the yellow warbler (Dendroica petechia aureola) from the Galápagos and Cocos Islands. Our analyses suggest aureola diverged from Central American lineages colonizing the Galápagos and Cocos Islands recently, likely less than 300 000 years ago. Within the Galápagos, patterns of genetic variation in microsatellite and mitochondrial markers suggest early stages of diversification. No intra-island patterns of morphological variation were found, even across steep ecological gradients, suggesting that either (i) high levels of gene flow may be homogenizing the effects of selection, (ii) populations may not have had enough time to accumulate the differences in morphological traits, or (iii) yellow warblers show lower levels of 'evolvability' than some other Galápagos species. By examining genetic data and morphological variation, our results provide new insight into the microevolutionary processes driving the patterns of variation.


Immunohistochemical localization of thyroid stimulating hormone induced by a low oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats.
We have investigated how a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects thyroid hormone regulation, especially in relation to the localization of thyroid stimulating hormone (TSH) in the pituitary and that of thyroxin (T4) of the thyroid in the rat. Female Sprague-Dawley rats were given a single oral administration of TCDD ranging from 1.0 to 4.0 microg/kg body weight (bw), and then tissue specimens were removed on day 7 post-administration. Thyroid hormone concentrations were measured in serum, and the expression of the TCDD-responsive genes, UDP-glucuronosyltransferase-1 (UGT1) and cytochrome P4501A1 (CYP1A1) were examined in the liver. TCDD administration resulted in an increase in both immunostaining intensity and the number of TSH-positive cells in the anterior pituitary. T4 was found to localize only in the follicular lumen of the thyroid in vehicle-treated control rats, while TCDD administration caused a foamy change in the colloid of some follicles, an indication of accelerating the biosynthesis of T4 in the thyroid. By morphometrical analysis, the ratio of parenchymal/lumenal area of the thyroid was found to increase in response to TCDD. TCDD treatment as low as 2.0 microg TCDD/kg bw induced a significant decrease in both serum total T4 (TT4) and free T4 (FT4) concentrations in the rats, with a significant increase in serum TSH levels in the 4.0 microg TCDD/kg bw rats. Serum total triiodothyronine (TT3) level was unchanged in all groups. The UGT1 gene was significantly induced at a TCDD dose as low as 1.0 microg/kg bw in a dose-dependent manner. TCDD concentrations in the serum, liver and adipose tissues were detected in a dose-related fashion. The present immunohistochemical results clearly support the earlier biochemical findings on the perturbation of the thyroid-pituitary axis by TCDD and suggest that UGT1 is an immediate target of a low TCDD exposure that triggers the perturbation.


Identification and some characteristics of the enzyme protein of the hormone-sensitive lipase from rat adipose tissue.
A tri-, di-, and monoacylglycerol-hydrolyzing enzyme from rat adipose tissue has been detergent-solubilized and separated from monoacylglycerol lipase (H. Tornqvist and P. Belfrage, 1976, J. Biol. Chem. 251, 813-819) and lipoprotein lipase by use of ion-exchange chromatography, broad and narrow pH range electrofocusing and gel chromatography. The final preparation contained several different proteins. One of these, with an apparent minimum molecular weight of 86,000 by SDS-gel electrophoresis, was identified as the enzyme protein of hormone-sensitive lipase: a) the enzyme activity was reproducibly stimulated 50-100% by incubation with cyclic AMP-dependent protein kinase, cyclic AMP and ATP-Mg2+; b) the relative intensity of the Mw 86,000 protein band, and only this, closely paralleled the enzyme activity during narrow pH range electrofocusing and during subsequent gel chromatography of the electrofocusing enzyme peak fraction; c) only the Mw 86,000 protein extensively incorporated 32p from [gamma-32P]ATP after incubation with protein kinase and cyclic AMP. The pI of the enzyme was 6.7, it had the same Stokes radius on Sephadex G 200 as IgG and was 50% inactivated by 10 micron HgCl2, 20 micron PCMB, 50 micron DFP, 10 mM NaF and non-ionic detergents above their critical micellar concentration.


A case of intraductal papillary mucinous tumour following recurrent attacks of pancreatitis lasting 26 years.
We report an interesting case of a patient with neither family nor personal history for pancreatic diseases that was admitted to our department in 1982, at the age of 25 years. At that time, medical history, absence of alcohol abuse, and radiological imaging suggested a diagnosis of idiopathic chronic pancreatitis. The patient underwent a left-pancreatectomy, with histological confirmation of chronic pancreatitis. He was asymptomatic until 1988, when episodes of pain arose, requiring a pancreatico-jejunostomy. No further problems ensued until 2004 when radiological investigation following pain-related symptoms revealed enormous dilation of the pancreatic duct. A pylorus-preserving pancreaticoduodenectomy resulting in total pancreatectomy was performed. Histological examination revealed an intraductal papillary mucinous non-invasive carcinoma. Review of the previously resected specimen revealed former misdiagnosis. This tumour usually affects an elderly population and nowadays is recognised as a possible cause of chronic obstructive pancreatitis. This report represents a slippery case of misdiagnosis and demonstrates that follow-up is always mandatory following a diagnosis of idiopathic chronic pancreatitis.


[Driver's license and diabetes. Legal and social medicine aspects].
The diagnosis of diabetes mellitus is accompanied by a lot of personal and social consequences for the patient himself. One of the most important problems is the influence of the disease on the patients driving skills. This aspect is discussed according to the recommendations of the German ministry of traffic, and advice is given for the diabetic patient taking part at the daily traffic as a car driver.


Characterization of functionally active gene fusions in human papillomavirus related oropharyngeal squamous cell carcinoma.
The Cancer Genome Atlas (TCGA) sequencing analysis of head and neck squamous cell carcinoma (HNSCC) recently reported on gene fusions, however, few human papillomavirus (HPV) positive samples were included, and the functional relevance of identified fusions was not explored. We therefore performed an independent analysis of gene fusions in HPV-positive oropharyngeal SCC (OPSCC). RNA sequencing was performed on 47 HPV-positive OPSCC primary tumors and 25 normal mucosal samples from cancer unaffected controls on an Illumina TruSeq platform. MapSplice2 was used for alignment and identification of fusion candidates. Putative fusions with less than five spanning reads, detected in normal tissues, or that mapped to the same gene were filtered out. Selected fusions were validated by RT-PCR and Sanger sequencing. Within 47 HPV-positive OPSCC tumors, 282 gene fusions were identified. Most fusions (85.1%) occurred in a single tumor, and the remaining fusions recurred in 2-16 tumors. Gene fusions were associated with significant up regulation of 16 genes (including EGFR and ERBB4) and down regulation of four genes (PTPRT, ZNF750, DLG2, SLCO5A1). Expression of these genes followed similar patterns of up regulation and down regulation in tumors without these fusions compared to normal tissue. Five of six gene fusions selected for validation were confirmed through RT-PCR and sequencing. This integrative analysis provides a method of prioritizing functionally relevant gene fusions that may be expanded to other tumor types. These results demonstrate that gene fusions may be one mechanism by which functionally relevant genes are altered in HPV-positive OPSCC.


Photothermogenetic inhibition of cancer stemness by near-infrared-light-activatable nanocomplexes.
Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/β-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.


Responses to direction of stimulus movement are different for somatosensory and visual cells in cat superior colliculus.
Direction selectivity is prominent among visual cells in the superior colliculus (SC). Its presumptive behavioral role raises the question of whether SC cells representing other sensory modalities involved in parallel behaviors also exhibit this property. The present experiments demonstrate that, apart from cells activated by vibrissae displacement, this property is poorly represented among somatosensory SC cells. Some somatosensory cells do exhibit movement asymmetries yet these asymmetries are not in opposite directions along the same axis, but rather among different axes (axis selective). These findings may reflect a fundamental difference in how SC cells representing these sensory modalities code movements across their respective receptor organs.


A hardware-based computational platform for Generalized Laguerre-Volterra MIMO model for neural activities.
A parallelized and pipelined architecture based on FPGA and a higher-level Self Reconfiguration Platform are proposed in this paper to model Generalized Laguerre-Volterra MIMO system essential in identifying the time-varying neural dynamics underlying spike activities. Our proposed design is based on the Xilinx Virtex-6 FPGA platform and the processing core can produce data samples at a speed of 1.33 × 10(6)/s, which is 3.1 × 10(3) times faster than the corresponding C model running on an Intel i7-860 Quad Core Processor. The ongoing work of the construction of the advanced Self Reconfiguration Platform is presented and initial test results are provided.


Correction to: Keeping pace with forestry: Multi-scale conservation in a changing production forest matrix.
In the original published article, the sentence "Nevertheless, semi-natural forest remnants continue to be harvested and fragmented (Svensson et al. 2018; Jonsson et al. 2019), and over 2000 forest-associated species (of 15 000 assessed) are listed as threatened on Sweden's red-list, largely represented by macro-fungi, beetles, lichens and butterflies (Sandström 2015)."under the section Introduction was incorrect. The correct version of the sentence is "Nevertheless, semi-natural forest remnants continue to be harvested and fragmented (Svensson et al. 2018; Jonsson et al. 2019), and approximately 2000 forest-associated species (of 15 000 assessed) are on Sweden's red-list, largely represented by macro-fungi, beetles, lichens and butterflies (Sandström 2015)."


Evaluation of nurses' theoretical knowledge in Basic Life Support: a study in a district Greek hospital.
Nurses are usually the first-responders in cases of in-hospital cardiac arrest. Their competence in Basic Life Support (BLS) is important in improving patient outcome. The purpose of this study was to evaluate the nurses' BLS knowledge in a small district hospital. Data was collected by an anonymous questionnaire, distributed to all nursing personnel in this hospital. The failure rate of the BLS theoretical questionnaire was 84%. Regarding self-assessment 10.3% of the participants rated their BLS knowledge as very good, whereas 31.2%, 44.2% and 14.3% of them rated it as good, moderate or not good respectively. This self-assessment did not correlate significantly with the final performance in the written test. No difference regarding the performance in the written test was observed between nurses who had participated in a refresher BLS course after graduation and those who had not. The nurses without any previous personal experience in the BLS had a higher probability to pass the written test. Our results indicate a low level of BLS knowledge among the study participants. Having an occasional refresher BLS course, or prior experience in BLS, does not affect the level of knowledge.


The prevalence of functional dyspepsia using Rome III questionnaire among chronic hepatitis C patients.
Hepatitis C virus (HCV) is a common chronic infection that is widely associated with symptoms of fatigue and abdominal pain. The aim of the present study was to determine the prevalence of functional dyspepsia (FD) among patients with hepatitis C. This study included 252 patients with chronic hepatitis C and 150 healthy volunteers. Clinical and laboratory data were recorded for every patient. All patients and controls were administered a questionnaire of FD according to Rome III criteria. The percentage of patients with FD was significantly higher in patients with chronic HCV than normal controls (65.9 % vs 28.7 %, respectively). In chronic HCV patients, post prandial distention syndrome (PDS) subtype was the predominant type (86.1 %). The percentage of patients with a high fibrosis score (F2-3) and raised ALT were significantly higher in patients with FD than in patients without FD (P < 0.001; P < 0.04; respectively). A multivariate regression analysis revealed a significant association between fibrosis score, BMI and FD CONCLUSION: FD is more prevalent in patients with chronic hepatitis C. Obese chronic HCV and those with higher fibrosis scores are more likely to have FD.


Clinical bonding of a single-step self-etching adhesive in noncarious cervical lesions.
The aim of this study was to evaluate the clinical retention to dentin of a single-step self-etching adhesive system. A total of 133 Class V restorations were placed with the self-etching primer Xeno III and a resin composite (Tetric Ceram) or a polyacid-modified resin composite (Dyract AP) in noncarious cervical lesions without intentional enamel involvement. The restorations were evaluated at baseline and then every 6 months during a 2-year follow-up. Dentin bonding efficacy was determined by the percentage of lost restorations. During the 2 years, 130 restorations could be evaluated. The cumulative loss rate at 2 years was 7.7%, with no significant differences between the two restorative materials. The self-etching adhesive fulfilled the 18-month full acceptance ADA criteria. The single-step self-etching adhesive showed acceptable clinical retention rates to dentin surfaces during the evaluation period independent of restorative material used.


Antigen-based therapies using ignored determinants of beta cell antigens can more effectively inhibit late-stage autoimmune disease in diabetes-prone mice.
As organ-specific autoimmune diseases do not become manifest until well-advanced, interventive therapies must inhibit late-stage disease processes. Using a panel of immunogenic peptides from various beta cell Ags, we evaluated the factors influencing the efficacy of Ag-based therapies in diabetes-prone NOD mice with advanced disease. The ability of the major beta cell autoantigen target determinants (TDs) to prime Th2 responses declined sharply between 6 and 12 wk of age, whereas the ability of immunogenic ignored determinants (IDs) of beta cell Ags to prime Th2 responses was unaffected by the disease process. The different patterns of TD and ID immunogenicity (even from the same beta cell Ag) may be due to the exhaustion of uncommitted TD-reactive, but not ID-reactive, T cell pools by recruitment into the autoimmune cascade. Therapeutic efficacy was associated with a peptide's immunogenicity and ability to promote Th2 spreading late in the disease process but not its affinity for I-Ag7 or its expression pattern (beta cell specific/nonspecific or rare/abundant). Characterization of some IDs revealed them to be "absolute" cryptic determinants. Such determinants have little impact on T cell selection, leaving large precursor T cell pools available for priming by synthetic peptides. Traditional Ag-based therapeutics using whole autoantigens or their TDs cannot prime responses to such determinants. These findings suggest a new strategy for designing more efficacious Ag-based therapeutics for late-stage autoimmune diseases.


Obesity: global epidemiology and pathogenesis.
The prevalence of obesity has increased worldwide in the past ~50 years, reaching pandemic levels. Obesity represents a major health challenge because it substantially increases the risk of diseases such as type 2 diabetes mellitus, fatty liver disease, hypertension, myocardial infarction, stroke, dementia, osteoarthritis, obstructive sleep apnoea and several cancers, thereby contributing to a decline in both quality of life and life expectancy. Obesity is also associated with unemployment, social disadvantages and reduced socio-economic productivity, thus increasingly creating an economic burden. Thus far, obesity prevention and treatment strategies - both at the individual and population level - have not been successful in the long term. Lifestyle and behavioural interventions aimed at reducing calorie intake and increasing energy expenditure have limited effectiveness because complex and persistent hormonal, metabolic and neurochemical adaptations defend against weight loss and promote weight regain. Reducing the obesity burden requires approaches that combine individual interventions with changes in the environment and society. Therefore, a better understanding of the remarkable regional differences in obesity prevalence and trends might help to identify societal causes of obesity and provide guidance on which are the most promising intervention strategies.


Assessment of myocardial oxidative stress in patients after myocardial revascularization.
A homogeneous group of six patients, who underwent coronary artery bypass surgery, was studied to determine the presence of oxidative stress caused by oxygen-derived free radicals and its relationship with reperfusion cell damage. Biopsies were performed before ischemia and 10 minutes after reperfusion. The samples were assayed for hydroperoxide-initiated chemiluminescence and histochemical succinic dehydrogenase activity; the specimens were also studied by electron microscopy. The preischemic biopsy specimens showed chemiluminescence of 40 +/- 2 (cpm/mg protein) x 10(3), normal succinic dehydrogenase activity (grade 4), and generally preserved ultrastructure (necrotic/normal cells 5/100). However, the reperfusion biopsy specimens showed an increase in chemiluminescence to 91 +/- 19 (cpm/mg protein) x 10(3) (p less than 0.025), a partial loss of enzymatic activity (grade 2.6), and ultrastructural changes characterized by mitochondrial swelling and focal myofibrillar disorganization (necrotic/normal cells: 15/100; p less than 0.001). These observations seem to indicate the presence of oxidative stress during reoxygenation, a situation that may play a major role in the genesis of reperfusion injury. It appears to be the first observation relating free radical-induced oxidative stress to reperfusion injury in humans.


[Fast-acting insulin - new developments towards more flexibility for the patient].
Post-prandial insulin secretion occurs under physiological conditions very fast and in adequate concentrations. This mechanism is impaired in patients with type 2 diabetes and severe increases of postprandial glucose levels may occur. In order to achieve physiological conditions and to avoid postprandial hyperglycemia, exogenous insulin and insulin analogues should be absorbed very fast and appropriate maximum concentrations should be reached very quickly. Overview RESULTS AND CONCLUSIONS: The development of new bolus insulins is focused on improved pharmacokinetic and pharmacodynamic properties. Not only new pharmaceutical formulations, but also different application sites and systems have been investigated. The latest innovations resulted in even faster acting insulins, which may offer patients improved postprandial glucose control and greater flexibility regarding meal planning.


Amplification of lymph node cell tube leukocyte adherence inhibition (LAI) reactivity by leukocyte adherence inhibition factor (LAIF).
This investigation examines the immunologic basis for specific antigen-induced tube leukocyte adherence inhibition (LAI) reactivity of draining lymph node cells (LNC) from dogs with canine transmissible venereal sarcoma (CTVS). CTVS regressor LNC, macrophage-depleted LNC, and enriched T lymphocyte fractions, but not enriched B lymphocyte fractions, were specifically reactive to CTVS antigen extract in direct tube LAI. In addition, regressor LNC amplified tube LAI responses by generating supernatants with leukocyte adherence inhibition factor (LAIF) activity for normal dog indicator LNC and enriched peripheral blood mononuclear cells (PBMC) in an indirect tube LAI assay. However, macrophage-depleted LNC and enriched T lymphocyte fractions failed to generate supernatants with LAIF activity, suggesting that macrophage accessory cells play a central role in the amplification of tube LAI. Interestingly, CTVS regressor peripheral blood leukocytes (PBL) and PBMC, which were specifically reactive in direct tube LAI, also failed to generate supernatants with LAIF activity. These findings demonstrate a distinction between LAIF-mediated amplification and direct tube LAI reactivity, and suggest that leukocyte populations with differing cellular proportions and from different immunologic compartments may participate in tube LAI via different mechanisms.


Fertility Preservation: A Tale of Two Testicles.
The transgender population has long been marginalized by society. Societal stigmata, fear to seek care, and dearth of provider knowledge regarding transgender health issues has caused disparities to widen. The purpose of this case study is to call to attention the often-overlooked aspect of transgender care: the importance of fertility preservation prior to undergoing therapy. 13 and 16-year old genetically XY patients presented to a tertiary care facility for gender affirmation. Both self-identified as female since a young age and successfully socially transitioned. Impending onset and/or progression of puberty prompted patients to seek hormonal therapy. Fortunately, physicians in transgender clinic were aware of fertility struggles after undergoing hormone therapy and referred for consultation. Sperm cryopreservation via open gonadal biopsy, tissue cryopreservation, and semen sample were discussed. Though invasive, biopsy relieves patients of the psychological impact of sample production and is indicated in pubertal immaturity. After further discussion with patients and parents, the 13-year-old decided to undergo testicular biopsy while the 16-year old opted for semen sample. Both patients had success and their genetic material was cryopreserved for future assisted reproduction. Gender affirming procedures and hormone therapy affect the long-term reproductive potential of transgender individuals. While cost concerns and insurance coverage regarding oncofertility is a prominent area of discussion, the transgender community is often excluded. With more individuals beginning medical and surgical therapy at a younger age, fertility preservation discussions are essential but often overlooked, depriving these individuals the joy of becoming a biological parent.


Have I argued with my family this week?": What questions do those with lived experience choose to monitor their bipolar disorder?
Electronic self-report mood monitoring tools for individuals with bipolar disorder (BD) are rapidly emerging and predominately employ predefined symptom-based questions. Allowing individuals to additionally choose what they monitor in relation to their BD offers the unique opportunity to capture and gain a deeper insight into patient priorities in this context. In addition to monitoring mood symptoms with two standardised self-rated questionnaires, 308 individuals with BD participating in the Bipolar Disorder Research Network True Colours electronic mood-monitoring tool for research chose to create and complete additional personalised questions. A content analysis approach was used to analyse the content of these questions. 35 categories were created based on the personalised questions with the most common being physical activity and exercise, anxiety and panic, sleep and coping/stress levels. The categories were grouped into six overarching themes 1) mental health; 2) behaviour and level of functioning; 3) physical wellbeing; 4) health behaviours; 5) active self-management; and, 6) interpersonal. The average age of the sample was around 50 years meaning our findings may not be generalisable to younger individuals with BD. Aspects of BD important to patients in relation to longitudinal monitoring extend well beyond mood symptoms, highlighting the limitations of solely relying on standardised questions/mood rating scales based on symptoms primarily used for diagnosis. Additional symptoms and aspects of life not necessarily useful diagnostically for BD may be more important for individuals themselves to monitor and have more meaning in capturing their own experience of changes in BD severity.


Baobab pulp authenticity and quality control by multi-imaging high-performance thin-layer chromatography.
Globalization of trade and increasing demand for baobab fruit pulp powder (Adansonia digitata) has led to more adulteration incidence with physically similar products, e.g. sifted cereal flours. In this study, 135 baobab samples drawn from trees in Kitui and Kilifi (Kenya) and North and South Kordofan (Sudan) were used as the reference and compared with adulterated (with 10-30% sifted rice, maize and wheat flours) baobab samples using multi-imaging by high-performance thin-layer chromatography. The ethanol - water extracts were separated on a normal phase. Any differences were detected via multi-imaging (UV/Vis/FLD) including diphenylamine alanine o-phosphoric acid, p-anisaldehyde sulfuric acid and p-amino benzoic acid reagents. Raffinose was identified as a marker compound for cereal-based adulteration. The method accuracy (recovery of 95%) and detection from 10-30% flour addition onwards are sufficient to curb economically motivated adulteration, to control product quality and to ensure consumer protection for local and international trade.


Up-regulation of interleukin-10 mRNA expression in peripheral leukocytes predicts poor outcome and diminished human leukocyte antigen-DR expression on monocytes in septic patients.
None of the parameters can predict the deterioration of sepsis early enough. A new predictor allowing earlier detection of changes in septic patients' condition is indispensable. We examined whether cytokine-related mRNA expression in peripheral leukocytes, cytokine blood level, and monocyte human leukocyte antigen (HLA)-DR expression rate could be useful predictors of deterioration of sepsis. Twenty septic patients were enrolled. mRNA expression levels were quantified using real-time reverse transcriptase-polymerase chain reaction and assessed by percent changes during the first 24 h. Cytokine blood levels on admission and day 3 and monocyte HLA-DR expression rate on day 3 were also measured. Correlations between each of these parameters, and between these parameters and outcome were analyzed. Among seven kinds of cytokines studied, only IL-10 mRNA level showed significant difference between survivors and non-survivors (P < 0.05). Mortality rate of interleukin (IL)-10 mRNA level up-regulated group was significantly higher than that of IL-10 mRNA level down-regulated group (P < 0.05). HLA-DR expression rate in non-survivors were significantly lower than that in survivors (P < 0.05). Although IL-10 blood level on day 3 significantly correlated with HLA-DR expression on day 3(r = 0.54, P < 0.05), IL-10 blood level on admission did not correlate with it. Contrarily, the degree of up-regulation of IL-10 mRNA expression during the first 24 h significantly correlated with the degree of diminished HLA-DR expression on day 3 (r = 0.78, P < 0.001). Up-regulated IL-10 mRNA expression and diminished HLA-DR expression could be indicators of poor outcome. Furthermore, IL-10 mRNA expression measurement could predict the onset of immunoparalysis indicated by diminished HLA-DR expression earlier than IL-10 blood level measurement, leading to earlier commencement of the treatment.


Positive remodeling is associated with vulnerable coronary plaque components regardless of clinical presentation: virtual histology-intravascular ultrasound analysis.
We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relation between coronary artery remodeling pattern and plaque components in 1133 patients. We divided the patients into two groups according to the remodeling pattern as positive remodeling (PR, remodeling index>1.05) (n=192) and intermediate remodeling (IR, remodeling index ≤ 1.05 and ≥ 0.95)/negative remodeling (NR, remodeling index<0.95) (n=941). VH-IVUS analysis classified the color-coded tissue into four major components: green (fibrotic, FT); yellow-green (fibro-fatty); white (dense calcium); and red (necrotic core, NC). Thin-cap fibroatheroma (TCFA) was defined as focal, NC-rich (≥ 10% of the cross-sectional area) plaques being in contact with the lumen in a plaque burden ≥ 40%. At the minimum lumen site, PR group had greater plaque plus media area (12.8 ± 4.9 vs. 9.9 ± 3.8mm(2), p<0.001) and greater %NC area (21.7 ± 12.3 vs. 18.2 ± 11.6%, p<0.001) and smaller %FT area (57.0 ± 14.5 vs. 59.4 ± 14.6%, p=0.037) compared with IR/NR group. PR group had greater plaque volume (188 ± 150 vs. 135 ± 130 mm(3), p<0.001) and greater %NC volume (19.1 ± 9.6 vs. 16.6 ± 9.2%, p=0.001) and smaller %FT volume (58.3 ± 11.7 vs. 60.6 ± 11.0%, p=0.009) compared with IR/NR group. PR group had more TCFA compared with IR/NR group (21% vs. 13%, p=0.006). Similar findings about plaque components were observed in terms of greater %NC volume and smaller %FT volume in PR group compared with IR/NR group in patients with both acute coronary syndrome and stable angina. VH-IVUS analysis demonstrates that PR was associated with more vulnerable plaque components compared with IR/NR regardless of their clinical presentation.


Chlorination of Irgasan DP300 and formation of dioxins from its chlorinated derivatives.
Irgasan DP300 (2,4,4'-trichloro-2'-hydroxydiphenyl ether) (I), an antimicrobial agent for use with fabrics, was easily chlorinated with sodium hypochlorite to give 2',3,4,4'-tetrachloro-2-hydroxydiphenyl ether (II), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (III) and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (IV). Irgasan DP300 and its chlorinated derivatives were readily converted into polychlorinated dibenzo-p-dioxins (PCDDs) by heating: Irgasan DP300 was converted into dichlorodibenzo-p-dioxin(s) (di-CDD, 42%); II into two trichlorodibenzo-p-dioxins (tri-CDDs, 22%) and three tetrachlorodibenzo-p-dioxins (tetra-CDDs, 46%); III into two tri-CDDs (44%), more than two tetra-CDDs (25%) and pentachlorodibenzo-p-dioxin(s) (penta-CDD, 1%); and IV into two tetra-CDDs (16%), trace amounts of penta-CDD(s) and four hexachlorodibenzo-p-dioxins (hexa-CDDs, 40%). Although UV irradiation of Irgasan DP300, II and III gave PCDDs, the amounts of PCDDs formed were much smaller than those obtained by heating. Moreover, PCDD was not detected in the UV irradiation of IV. The identified products suggested that disproportionation of chlorine atom(s) occurred in the photolysis.


Numerical judgments with Kanji and Kana.
Native Japanese speakers were timed to judge the numerically larger of two numbers, written either in Kanji (an ideographic script) or in Kana (a syllabic script). For Kanji, irrelevant variations in the physical size of the numbers speeded reaction time in one condition and slowed it in another. Such variations only slowed processing for Kana, except when subjects had previously performed with Kanji. For both scripts, reaction time varied with the numerical difference between the two numbers but not in an identical manner. The implications of the findings are considered.


Adrenal incidentalomas and effectiveness of patient pathway transformation.
A total of 10% of older individuals harbour adrenal incidentalomas and need dedicated adrenal CT to exclude malignancy and biochemical evaluation. These investigations tax medical resources, and diagnostic delay may cause anxiety for the patient. We implemented a no-need-to-see pathway (NNTS) in which low-risk patients only attend the clinic if adrenal CT or hormonal evaluation is abnormal. We investigated the impact of a NNTS pathway on the share of patients not requiring an attendance consultation, time to malignancy and hormonal clarification, and time to end of investigation. We prospectively registered adrenal incidentaloma cases (n = 347) and compared them with historical controls (n = 103). All controls attended the clinic. A total of 63% of cases entered and 84% completed the NNTS pathway without seeing an endocrinologist; 53% of consultations were avoided. Time-to-event analysis revealed a shorter time to clarification of malignancy (28 days; 95% confidence interval (CI): 24-30 days versus 64 days; 95% CI: 47-117 days) and hormonal status (43 days; 95% CI: 38-48 days versus 56 days; 95% CI: 47-68 days) and a shorter time to end of pathway (47 days; 95% CI: 42-55 days versus 112 days; 95% CI: 84-131 days) in cases than controls (p ≤ 0.01). We demonstrated that NNTS pathways may be an efficient way of handling the increased burden of incidental radiological findings, avoiding 53% of attendance consultations and achieving a shorter time to end of pathway. Supported by a grant from Regional Hospital Central Denmark, Denmark. The study was approved by the institutional review boards of all participating hospitals. Not relevant.


Communication, self-esteem and prolonged grief in parent-adolescent dyads, 1-4 years following the death of a parent to cancer.
Talking and grieving together may be advantageous for maintaining belief in a meaningful future and can help bereaved adolescents and their parents to cope better with the situation. The aim of this study was to explore communication, self-esteem and prolonged grief in adolescent-parent dyads, following the death of a parent to cancer. This study has a descriptive and comparative design. Twenty family dyads consisting of parentally bereaved adolescents (12-19 years) and their widowed parents completed the Parent and Adolescent Communication Scale, Rosenberg Self-Esteem Scale and Prolonged Grief-13, 1-4 years following the death of a parent. Twelve family dyads reported normal-high parent-adolescent communication, 11 dyads rated normal-high self-esteem. Two adolescents and three parents scored above the cut-off for possible prolonged grief disorder (≥35), none of these were in the same dyads. There was a difference (p < .05) between boys (mean 40.0) and girls (mean 41.9) with regard to open family communication, as assessed by parents. Girls reported lower self-esteem (mean 26.0) than boys (mean 34.1, p < .01). This study provides insights from parentally bereaved families which indicate that despite experiencing the often-traumatic life event of losing a parent or partner, most participants reported normal parent-adolescent communication, normal self-esteem and few symptoms of prolonged grief. The potential usefulness of identifying families who may need professional support in family communication following the death of a parent is discussed.


Chemical Composition and Antibacterial Activity of the Lippia origanoides Kunth Essential Oil from the Carajás National Forest, Brazil.
Species of the genus Lippia are rich in essential oils and have shown antibacterial properties, which may be related to oils' chemical composition. The present work aimed to evaluate the antimicrobial potential of Lippia origanoides Kunth against two bacteria strains: Escherichia coli and Staphylococcus aureus. Leaf essential oils were obtained by hydrodistillation in a modified Clevenger-type apparatus, and their chemical composition was determined by gas chromatography coupled to mass spectrometry (GC/MS) and flame ionization detection (GC/FID). We identified 28 compounds, representing 98.87% of the total concentration of the essential oil. The compounds identified at the highest concentrations were 1,8-cineole (35.04%), carvacrol (11.32%), p-cymene (8.53%), α-pinene (7.17%), and γ-terpinene (7.16%). The leaf essential oil of L. origanoides showed antibacterial action on biological isolates of Escherichia coli and Staphylococcus aureus. For Escherichia coli, the oil presented bactericidal action at concentrations of 5-20 μL/mL. Regarding Staphylococcus aureus, the bactericidal effect was noted at 20 μL/mL and the bacteriostatic action was noted around 2.5-10 μL/mL. Given the results obtained, L. origanoides essential oil showed promising biological potential against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, thus encouraging further studies on substances isolated from this species to contribute to the development of new antimicrobial drugs.


Quantitative assessment of pulmonary vascular resistance and reactivity in children with pulmonary hypertension due to congenital heart disease using a noninvasive method: new Doppler-derived indexes.
We assessed the usefulness of transthoracic Doppler-derived indexes obtained in the proximal pulmonary artery (PA) branch for estimating pulmonary vascular resistance (PVR) in 45 children with congenital heart disease (CHD) and 23 normal control subjects. The acceleration time, inflection time (InT), deceleration index, and peak velocity, which were measured from the systolic PA flow velocity curve obtained at the sites of the main PA, and right and left PA, were compared with the PVR in patients with CHD. In addition, changes in either Doppler-derived indexes or PVR during 100% oxygen administration were compared in 22 patients showing a baseline PVR >or=4.6 U/m(2) (high PVR). The heart-rate-corrected InT (InTc) values obtained in the left PA in the high PVR group were significantly lower than those in the main PA (4.7 +/- 1.5 vs. 7.5 +/- 3.0; p < 0.001). The InTc obtained from the left PA separated patients with high and low PVR (4.7 +/- 1.4 vs. 9.9 +/- 2.4; p < 0.001) and no significant differences in InTc were found between the low PVR and the control groups. An increase in InTc to >6 during 100% oxygen administration for the high PVR group indicated good PA reactivity with a sensitivity of 93%, specificity of 100%, and agreement of 95% (kappa = 0.83). Moreover, this InTc index correlated inversely with PVR (r = -0.80). In conclusion, our method can noninvasively separate high and low PVR and assess the PA reactivity for high PVR in children with CHD.


Studies of the plasticizing effect of different hydrophilic inorganic salts on starch/poly (vinyl alcohol) films.
The effects of different inorganic salts LiCl, MgCl2·6H2O, CaCl2, and AlCl3·6H2O on the crystalline, thermal, water vapor barrier, and tensile properties of starch/PVA films were studied. The high plasticizing efficiency of all these four inorganic salts for starch/PVA film was confirmed by the obtained results. These four salts all had a good compatibility with starch/PVA within the content of 15 wt% and starch/PVA became completely miscible with the addition of 15 wt% inorganic salts. All these four salts had a strong destroying effect on the crystals of starch and PVA. Among these four salts, AlCl3·6H2O had the largest negative effect on the thermal stability of starch/PVA and LiCl had the largest improving effect on the water sorption rate of starch/PVA film. On the whole MgCl2·6H2O and CaCl2 were the more suitable plasticizer for starch/PVA film among these four inorganic salts. With the addition of 15 wt% MgCl2·6H2O and CaCl2, the elongation at break of starch/PVA film could reach to 418.83% and 434.80%, respectively.


Cadmium perturbed lipid profile and induced liver dysfunction in mice through phosphatidylcholine remodeling and promoting arachidonic acid synthesis and metabolism.
Cadmium ion (Cd2+) exposure has been reported to associate with the prevalence of dyslipidemia, and contribute to the initiation and progression of nonalcoholic fatty liver disease (NAFLD). However, Cd2+ exposure perturbed specific metabolic pathways and underlying mechanisms are still unclear. In the present study, through lipidomics analyses of differential metabolites in serum between the Cd2+-exposed mice and the control group, 179 differential metabolites were identified, among which phosphatidylcholines (PCs) accounted for 49 % metabolites. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment assay indicates that PCs participate in the metabolic pathways, including the Arachidonic Acid (AA) metabolism, which also could be potential NAFLD biomarkers. Moreover, in vivo and in vitro results suggested that Cd2+ exposure induced PC synthesis and remodeling, and increased AA level by promoting fatty acid desaturase 1 (FADS1) to catalyze synthesis process instead of cytosolic phospholipase A2 (cPLA2) mediated release pathway. Inhibition of FADS1 by T3364366 could reverse Cd-induced AA, prostaglandin E2 (PGE2) and triglyceride (TAG) levels, and it also reduce cisplatin resistance in HepG2 cells. This study provides new evidence of Cd2+-induced dyslipidemia and reveals underlying molecular mechanism involved in liver dysfunction of Cd2+ exposure.


A multicentre study comparing two methods for serum free light chain analysis.
Serum free light chain analysis is now well established in the investigation of monoclonal gammopathies. In the UK there has, until recently, been a single supplier of kits for such analysis. Recently, a second method using monoclonal antisera was introduced. We have compared the performance of these two kits in four routine laboratories. Samples submitted for routine analysis (327 samples, 258 [79%] from patients with B-cell lymphoproliferative disease) for serum free light chains were tested by both technologies (Freelite, Binding Site and N Latex FLC, Siemens), according to the manufacturers' instructions. Qualitative data were available by both methods on 313 samples for serum free kappa chains and 324 samples for lambda free light chains. We found poor correspondence of 81% for kappa and 74% for lambda. Five percent of samples were significantly discordant in these assays. These assays perform very differently in clinical practice. They cannot be used interchangeably, especially if monitoring patient responses to therapy.


Environmental geochemistry study of arsenic in Western Hunan mining area, P.R. China.
The geochemical characteristics of arsenic in the soil of the Western Hunan mining area of P.R. China were systematically studied. The results show that the strata of Western Hunan are rich in arsenic and that Western Hunan is a geochemically abnormal region for arsenic. The experimental study on speciation in the strata also indicates that the speciation of arsenic in the Neoproterozoic-Cambrian strata are mainly easily transferred speciation (exchangeable, carbonate-bound, sulfides-bound), which are approaching or exceed 60%. Arsenic content in the main soil of Western Hunan is in the range of 8.8-22.8 mug g(-1), the mean value is 16.1 mug g(-1), which is larger than the arsenic background value of Hunan soil. The distribution of rock with high arsenic content or high easily transferred arsenic speciation is consistent with the distribution of high arsenic content soil. In the mining region, part soils and river/brook waters were polluted by mine tailings and mining/smelting waste water. The arsenic content in polluted paddy soils and river/brook water is 46.26-496.19 microg g(-1), 0.3-16.5 mgL(-1), respectively. The positive abnormality and pollution of arsenic in the soil and water affects the arsenic content of the crop and the inhabitants' health.


Stable, three degree-of-freedom myoelectric prosthetic control via chronic bipolar intramuscular electrodes: a case study.
Modern prosthetic hands are typically controlled using skin surface electromyographic signals (EMG) from remaining muscles in the residual limb. However, surface electrode performance is limited by changes in skin impedance over time, day-to-day variations in electrode placement, and relative motion between the electrodes and underlying muscles during movement: these limitations require frequent retraining of controllers. In the presented study, we used chronically implanted intramuscular electrodes to minimize these effects and thus create a more robust prosthetic controller. A study participant with a transradial amputation was chronically implanted with 8 intramuscular EMG electrodes. A K Nearest Neighbor (KNN) regression velocity controller was trained to predict intended joint movement direction using EMG data collected during a single training session. The resulting KNN was evaluated over 12 weeks and in multiple arm posture configurations, with the participant controlling a 3 Degree-of-Freedom (DOF) virtual reality (VR) hand to match target VR hand postures. The performance of this EMG-based controller was compared to a position-based controller that used movement measured from the participant's opposite (intact) hand. Surface EMG was also collected for signal quality comparisons. Signals from the implanted intramuscular electrodes exhibited less crosstalk between the various channels and had a higher Signal-to-Noise Ratio than surface electrode signals. The performance of the intramuscular EMG-based KNN controller in the VR control task showed no degradation over time, and was stable over the 6 different arm postures. Both the EMG-based KNN controller and the intact hand-based controller had 100% hand posture matching success rates, but the intact hand-based controller was slightly superior in regards to speed (trial time used) and directness of the VR hand control (path efficiency). Chronically implanted intramuscular electrodes provide negligible crosstalk, high SNR, and substantial VR control performance, including the ability to use a fixed controller over 12 weeks and under different arm positions. This approach can thus be a highly effective platform for advanced, multi-DOF prosthetic control.


Body surface potential maps with low-level exercise in isolated left anterior descending coronary artery disease.
One hundred and twenty-lead body surface potential maps (BSPMs) were recorded at rest, at immediate cessation of exercise and after 1 (early) and 5 minutes (late) of recovery in 14 patients with isolated, critical, left anterior descending (LAD) coronary artery stenosis. Exercise endpoints, at an average peak rate of 98 +/- 13, were usual pain worsening in 13 LAD patients, and diagnostic ST depression in lead V5 in 1 patient. Twelve patients also had positive thallium scans. BSPMs were also recorded in 8 normal subjects who exercised to peak heart rates similar to those of the LAD subjects. Spatially, there were similar exercise changes in QRS and ST-segment integral patterns over the precordium and inferior torso in both groups. These were transient in the control group but persisted to late recovery in the LAD group, particularly for ST integral. Quantitatively, multivariate analysis revealed significant temporal differences between the 2 groups. However, the only independent BSPM variable was the sum of ST integral decrease, averaging --2,323 +/- 1,809 microV.s for normal patients between rest and immediate cessation of exercise, compared with -3,828 +/- 2,329 microV.s for the LAD patients (p less than 0.05). Late recovery minus rest difference averaged -1,264 +/- 1,080 microV.s for normal subjects and -2,575 +/- 1,844 microV.s for LAD patients (p less than 0.01). To control for the physiologic changes of exercise, the ST integral temporal differential maps of the normal subjects were subtracted from those of the LAD patients and the sum of negative intergroup differences was assumed to reflect only ischemia. Correlation of ST integral ischemia values at immediate cessation of exercise and late recovery was high (r = 0.88); however, intertechnique correlations of the BSPM variables with quantitative angiographic scores and thallium perfusion scan scores revealed generally low r values (range 0 to 0.52). These data demonstrate that ischemic repolarization changes are detectable and quantifiable by BSPM at low levels of cardiac stress in patients with 1-vessel disease when the usual electrocardiographic criteria of myocardial ischemia are frequently absent. The data further suggest that ST integral changes reflective of myocardial ischemia persist well after the exercise recovery period and that they are complementary to, rather than substitutionary for, other indirect measures of myocardial ischemia.


Ovarian hormone: lack of effect on reproductive structures of female Asian musk shrews.
Uterine and vaginal weights and histologies are not altered by ovariectomy or estrogen treatment in the Asian musk shrew (Suncus murinus). In addition, ovariectomized shrews mate. Thus, the role of ovarian hormones in the control of the reproductive status of this species does not conform to the accepted mammalian pattern.


Chill out: Environmentally relevant cooling challenge does not increase telomere loss during early life.
In vertebrates, exposure to diverse stressors during early life activates a stress response that can initiate compensatory mechanisms or promote cellular damage with long-term fitness consequences. A growing number of studies associate exposure to stressors during early life with increased damage to telomeres (i.e., promoting the shortening of these highly conserved, repeating sequences of non-coding DNA at chromosome ends). However, some studies show no such relationship, suggesting that the nature, timing, and context of these challenges may determine the degree to which physiological mediators of the stress response act in a damage-mitigating or damage promoting way in relation to telomere dynamics. In free-living eastern bluebirds (Sialia sialis), we have previously demonstrated that bouts of offspring cooling that occur when brooding females leave the nest increase at least one such physiological mediator of the stress response (circulating glucocorticoids), suggesting that variation in patterns of maternal brooding may result in different impacts on telomere dynamics at a young age. Here we experimentally tested whether repeated bouts of ecologically relevant offspring cooling affected telomere dynamics during post-natal development. Rates of telomere shortening during the nestling stage were not affected by experimental cooling, but they were affected by brood size and the rate of growth during the nestling stage. Our data suggest that the effects of developmental stress exposure on offspring telomeres are often context-dependent and that not all challenges that increase physiological mediators of stress result in damage to telomeres. Under some conditions, physiological mediators of stress may instead act as protective regulators, allowing for optimization of fitness outcomes in the face of environmental challenges.


Substantiating the concept of work strain: its implication for the assessment of work stressors.
To assess which work stressors are substantially contributing to work strain and examine their relative contribution. We prospectively examined the association between work stressors and work strain, which was defined as employees reporting ill due to work stress. Relevant work stressors were combined into a stressor score with each stressor having its own relevance. Standardized odds ratios (SORs) were calculated using logistic regression analysis and used to compare the associations obtained between already existing scales and the stressor score with work strain. The stressor score yielded an SOR of 1.89 (95% confidence interval: 1.49 to 2.41) for work strain, while psychological demands (JCQ) yielded an SOR of 1.46 (95% confidence interval: 1.09 to 1.88) for work strain. We were able to extend and substantiate the range of relevant work stressors into a more comprehensive measure, which should be used to optimize prevention strategies.


Outer Nuclear Layer as the Main Predictor to Anatomic Response to Half Dose Photodynamic Therapy in Chronic Central Serous Retinopathy.
To evaluate the predictors for subretinal fluid resorption in patients with chronic central serous retinopathy (cCSR) submitted to half-dose photodynamic therapy (HD-PDT). Observational, longitudinal, and retrospective study of patients with cCSR submitted to HD-PDT in a tertiary ophthalmology department in Portugal between January 2015 and February 2018. Best-corrected visual acuity (BCVA) and SD-OCT at baseline and 12 ± 3 months after treatment were performed. The central macular thickness (CMT), outer nuclear layer (ONL) thickness, integrity of the external limiting membrane (ELM), ellipsoid (EZ) and interdigitation zone (IZ), subretinal fluid (SFR) height, and choroidal thickness (CT) were evaluated. Patients were classified into responders and nonresponders based on SRF resorption. Sixty-one eyes of 42 patients were included; 75.4% were classified as responders. Final BCVA was significantly better in responders (p=0.002). The baseline ONL was thicker (p < 0.01) and intact ELM (67.2% vs. 16.4%), EZ (49.2% vs. 8.2%), and IZ (31.2% vs. 1.6%) were more prevalent in responders than in nonresponders. Anatomic response was correlated with a thicker ONL (rs (59) = 0.416, p=0.001 ∗ ), intact ELM (rs (59) = 0.261, p=0.04 ∗ ), EZ (rs (59) = 0.278, p=0.03 ∗ ), and IZ (rs (59) = 0.318, p=0.01 ∗ ). Binary logistic regression showed that a thicker ONL thickness increased the chance of an anatomic response to HD-PDT. The other evaluated retinal layers did not have statistical significance in the binary regression model. cCSR responders to HD-PDT have a better final BCVA, a thicker baseline ONL, and an intact baseline ELM, EZ, and IZ. However, ONL was the only predictor in a logistic regression model for SRF resorption.


Cross-sectional imaging following surgical interventions for stress urinary incontinence in females.
Stress urinary incontinence (SUI) is a condition in which the weakness of the pelvic floor muscles causes unintentional loss of urine. For patients who are unable to achieve symptomatic improvement from lifestyle modification and pharmacotherapy, surgical placement of the pelvic slings or the use of urethral bulking agents has been shown to provide tremendous symptomatic improvement. Learning to recognize the pelvic slings and to identify their complications on imaging is invaluable; however, this is challenging because of the change in the local anatomy after surgical placement of the sling. In this paper, we present CT and MR imaging to demonstrate the surgical and non-surgical treatments of female SUI and their complications. Through this pictorial essay, our goal is to familiarize radiologists with recognizing the various forms of treatment for SUIs, the relevant pelvic anatomy, and complications that may occur secondary to the surgical placement of the pelvic slings.


Leaching of cyanogenic glucosides and cyanide from white clover green manure.
Use of crops for green manure as a substitute for chemical fertilizers and pesticides is an important approach towards more sustainable agricultural practices. Green manure from white clover is rich in nitrogen but white clover also produces the cyanogenic glucosides (CGs) linamarin and lotaustralin; CGs release toxic hydrogen cyanide (HCN) upon hydrolysis which may be utilized for pest control. We demonstrate that applying CGs in the form of a liquid extract of white clover to large columns of intact agricultural soils can result in leaching of toxic cyanide species to a depth of at least 1m. Although degradation of the CGs during leaching proceeded with half lives in the interval 1.5-35 h depending on soil characteristics, a fraction of the applied CGs (0.9-3.2%) was recovered in the leachate as either CGs or toxic cyanide species. Detoxification of the HCN formed was rapid in soil and leachate from both sandy and loamy soil. However, 30% of the leachate samples exceeded the EU threshold value of 50 micrgl(-1) total cyanide for drinking water and 85% exceeded the US threshold of 5 micrgl(-1) for cyanide chronic ecotoxicity in fresh water. This study demonstrates that even easily degradable natural products present in crop plants as defense compounds pose a threat to the quality of groundwater and surface waters. This aspect needs consideration in assessment of the risk associated with use of crops as green manure to replace chemical fertilizers and pesticides as well as in genetic engineering approaches to design crops with improved pest resistance.


Detection and microsequencing of juvenile hormone-binding proteins of an insect by the use of an iodinated juvenile hormone analog.
An [125I]iodinated juvenile hormone (JH) analog can be used as a sensitive and highly selective probe for the visualization of high-affinity, (JH)-specific binding proteins from insect hemolymph samples. The proteins can be detected in their native form using a two-dimensional (isoelectric focusing then native gradipore gel) separation of the crude protein mixture containing the 125I-labeled iodinated JH analog. The proteins can be transferred to activated glass fiber paper by electroblotting, and the location of the bound gamma-emitter can be found by exposure of the dried gel or the electroblot to X-ray film. The radiolabeled protein spot can be excised from the Coomassie-stained glass fiber paper and subjected directly to gas-phase N-terminal amino acid sequencing. This non-destructive, non-denaturing technique may have wide applicability in identifying and sequencing ligand-specific binding proteins in complex mixtures.


A comparison of the effects of chromate, molybdate and cadmium oxide on respiration in the yeast Saccharomyces cerevisiae.
Growth of Saccharomyces cerevisiae on non-fermentable medium was more sensitive to inhibition by chromate than growth on fermentable medium. Chromate was selectively toxic against oxygen uptake in cells grown in non-fermentable medium and also induced petite mutations. CdO demonstrated similar but lesser effects on growth and respiration. However, molybdate had little toxicity to yeast non-fermentable growth and stimulated oxygen uptake in cells grown in fermentable and non-fermentable media. These results suggest that chromate, a carcinogen, may act more directly against the mitochondria of S. cerevisiae than related chemical species, CdO and molybdate.


Methods to determine HIV-1 ex vivo fitness.
The fitness of human immunodeficiency virus type-1 (HIV-1) appears to be an important piece of the puzzle in understanding the global HIV-1 epidemic and disease progression in infected individuals. We have developed a dual infection/competition assay followed by a sensitive heteroduplex tracking assay (HTA) to measure the relative fitness of any HIV-1 isolate. Differences in fitness between wild-type and drug-resistant HIV-1 isolates can also be used as indicators of the emergence of drug-resistant isolates. This chapter describes the methods utilized to measure viral fitness (relative replicative capacity) during growth competition experiments. HTA is used to evaluate the production of HIV-1 variants in a competition, which can then be used to estimate ex vivo viral fitness.


Role of acoustic striae in hearing: reflexive responses to elevated sound-sources.
This report is the fourth in a series describing the results of ablation-behavior experiments directed to the ascending output of the cochlear nuclei as it is conducted centrally within the acoustic striae. This fourth report focuses on the unique physiology of the fusiform or 'output' cells of the dorsal cochlear nucleus whose axons course through the dorsal acoustic stria (DAS). Because electrophysiological studies have shown that the cues for sensing the elevation of a sound source would seem to be best analyzed by the dorsal cochlear nucleus and projected centrally via its DAS, we tested normal cats and cats deprived of DAS for their ability to orient to elevated sources of broad-band noise. For behavioral testing, we made use of reflexive or unconditioned orienting responses to elevated sound sources using a similar method to one we have used previously for azimuth testing (Thompson GC, Masterton RB. Brainstem auditory pathways involved in reflexive head orientation to sound. J Neurophysiol 1978;41:1183-1202). The results show that cats deprived of their DAS do indeed have a marked deficit in their ability to orient to an elevated sound source. Further behavioral testing indicated that this deficit is not the secondary result of an attentional or peripheral motor deficit. Although the present results do not prove that the reflexive deficit is strictly auditory in nature, the deficit is notable in that it is the only one yet known to result from a lesion of the dorsal cochlear nucleus or its central projections.


Analysis of 2-D motion tracking in ultrasound with dual transducers.
We study displacement and strain measurement error of dual transducers (two linear arrays, aligned orthogonally and coplanar). Displacements along the beam of each transducer are used to obtain measurements in two-dimensions. Simulations (5MHz) and experiments (10MHz) are compared to measurements with a single linear array, with and without angular compounding. Translation simulations demonstrate factors of 1.07 larger and 8.0 smaller biases in the axial and lateral directions respectively, for dual transducers compared to angular compounding. As the angle between dual transducers decreases from 90° to 40°, for 1% compression simulations, the lateral RMS error ranges from 2.1 to 3.9μm compared to 9μm with angular compounding. Simulation of dual transducer misalignment of 1mm and 2° result in errors of less than 9μm. Experiments demonstrate factors of 3.0 and 5.2 lower biases for dual transducers in the axial and lateral directions respectively compared to angular compounding.


The construction of the SEDAS: a new suicide-attitude questionnaire.
Only two scales exist for measuring attitudes towards suicidal behaviour. Because of theoretical and methodological limitations of both scales, the SEDAS was constructed to offer an alternative instrument. The semantic differential scale, from which the SEDAS was devised, consisted of 36 items (pairs of adjectives) constructed to measure attitudes towards suicidal behaviour of different actors in various situations. It was administered to 142 Dutch SOS-telephone volunteers for seven different actor/situation sets. Item analysis reduced the number of suitable items to 15. Simultaneous component analysis revealed two dimensions on which the actor/situation sets were scored: health/illness and acceptance/rejection, jointly accounting for 47% of variance. Psychometrics of the instrument in terms of internal consistency (values between 0.70 and 0.86), item-rest correlation and test-retest correlation (between 0.63 and 0.87) are acceptable to good. The SEDAS may be of value in population surveys, and facilitate effect evaluation of staff training and suicide prevention programmes.


Extracellular histidine residues identify common structural determinants in the copper/zinc P2X2 receptor modulation.
To assess the mechanism of P2X2 receptor modulation by transition metals, the cDNA for the wild-type receptor was injected to Xenopus laevis oocytes and examined 48-72 h later by the two-electrode voltage-clamp technique. Copper was the most potent of the trace metals examined; at 10 microm it evoked a 25-fold potentiation of the 10 microm ATP-gated currents. Zinc, nickel or mercury required 10-fold larger concentrations to cause comparable potentiations, while palladium, cobalt or cadmium averaged only 12- and 3-fold potentiations, respectively. Platinum was inactive. The non-additive effect of copper and zinc at 10-100 microm suggests a common site of action; these metals also shifted to the left the ATP concentration-response curves. To define residues necessary for trace metal modulation, alanines were singly substituted for each of the nine histidines in the extracellular domain of the rat P2X2 receptor. The H120A and H213A mutants were resistant to the modulator action of copper, zinc and other metals with the exception of mercury. Mutant H192A showed a reduction but not an abrogation of the copper or zinc potentiation. H245A showed less affinity for copper while this mutant flattened the zinc-induced potentiation. Mutant H319A reduced the copper but not the zinc-induced potentiation. In contrast, mutants H125A, H146A, H152A and H174A conserved the wild-type receptor sensitivity to trace metal modulation. We propose that His120, His192, His213 and His245 form part of a common allosteric metal-binding site of the P2X2 receptor, which for the specific coordination of copper, but not zinc, additionally involves His319.


An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD.
In chronic obstructive pulmonary disease (COPD) which consists of emphysema and chronic bronchitis, alveolar tissue and/or bronchiolar walls are progressively destroyed. This suggests cell death by necrosis and/or apoptosis although no direct evidence of apoptosis has been reported. It was speculated that the apoptosis-related factors are associated with the progression of COPD. Fas/Apo-1 receptor (Fas), Fas ligand (Fas-L) and soluble Fas ligand (sFas-L) are inducers, while soluble Fas (sFas) is an inhibitor of apoptosis. In this study, plasma sFas and sFas-L were measured in 19 COPD patients receiving supplemental O2 (severe COPD) and 20 COPD patients not receiving supplemental O2 (mild/moderate COPD). Twenty-two age- and sex-matched healthy volunteers (healthy controls) and 20 patients receiving supplemental O2 and with level of hypoxaemia similar to severe COPD due to other pulmonary diseases (disease controls) were also examined. Plasma sFas-L was within normal limits in all groups. Plasma sFas levels were similar among healthy controls, disease controls, and mild/moderate COPD patients, but significantly increased in severe COPD (2.6 +/- 1.1, 2.6 +/- 0.2, 2.8 +/- 0.2 and 4.8 +/- 1.0 ng ml-1, respectively). Although PaO2 was lower in severe COPD than in mild/moderate COPD, and PaCO2 was higher in severe COPD than in mild/moderate COPD, they were close between severe COPD and disease controls. Tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) were increased in patients with COPD, but were similar in both severe and mild/moderate COPD patients. We conclude that increased plasma sFas, which is independent of hypoxaemia, and increases in PaCO2, TNF-alpha, IL-6 and inflammation, may be associated with progression of COPD.


Narratives about resuscitation--family members differ about presence.
Healthcare professionals disagree about admitting family members into the resuscitation room. The aim of this study was to illuminate family members' experiences and views about being present in the resuscitation room with a relative requiring resuscitation. Seventeen family members were interviewed. Their narratives were analysed using content analysis. The main theme was interpreted as family members being "afraid of disturbing the resuscitation efforts, meaning that the most important person for them was the patient". Three groups of persons were in focus: patients, family members, and healthcare professionals. The theme related to the patient was "to be caring for the good of oneself and others" describing what family members believed the patient would want and what they themselves would have wanted if in the same situation. The themes related to family members were "to be dependent on the interplay between trusting oneself and advocating the patient and to be sensitive to one's own emotions and to be reasonable". The theme related to healthcare professionals was "to submit to or ignore the guidance of the healthcare professionals". Family members differ about their presence in the resuscitation room. Omnipresent in the narratives was being afraid of disturbing the resuscitation efforts.


A spider (Araneus ventricosus) chymotrypsin inhibitor that acts as an elastase inhibitor and a microbial serine protease inhibitor.
Spider-derived Kunitz-type serine protease inhibitors have been shown to exhibit plasmin and elastase inhibition activity and potassium channel blocking activity, but thus far, no additional roles for spider-derived chymotrypsin inhibitors have been elucidated. In this study, a spider (Araneus ventricosus) chymotrypsin inhibitor (AvCI) that acts as an elastase inhibitor and a microbial serine protease inhibitor was identified. AvCI is a 70-amino acid mature peptide that displays eight conserved cysteine residues and a P1 lysine residue. Recombinant AvCI expressed in baculovirus-infected insect cells demonstrated inhibitory activity against chymotrypsin (Ki 49.85 nM), but not trypsin, which defines a role for AvCI as a spider-derived chymotrypsin inhibitor. AvCI also exhibited inhibitory activity against microbial serine proteases such as subtilisin A (Ki 20.51 nM) and proteinase K (Ki 65.42 nM). Furthermore, AvCI exhibited no detectable inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or plasmin; however, AvCI strongly inhibited human neutrophil elastase (Ki 8.74 nM) and porcine pancreatic elastase (Ki 11.32 nM), indicating that AvCI acts as an anti-elastolytic factor. These findings constitute molecular evidence that AvCI acts as an inhibitor against chymotrypsin, microbial serine proteases, and elastases. This paper provides a novel view of the functions of a spider-derived chymotrypsin inhibitor.


The effect of topical agents on haematopoiesis following thermal injury: studies on an animal model.
Several investigators have described 'toxins' in the serum of burned patients that result in systemic alterations and in an overall breakdown of host defences. One of these toxins isolated from the burn eschar resulted in 80 per cent mortality when injected into non-burned mice. However, if the eschar was pretreated with cerium before isolating the toxin, the mortality in the recipients decreased. This experiment suggested that the cerium neutralized the toxin. We have partially isolated from the serum of burned patients and mice a substance that inhibits erythroid colony formation in vitro. To test if cerium neutralized this erythroid inhibitor, we applied cerium or silver nitrate to the eschar of a mouse model of thermal injury. We found that neither agent altered the level of inhibitor or any of the granulocyte or erythroid parameters measured.


Does abnormal Doppler on cranial ultrasound predict disability in infants with hypoxic-ischaemic encephalopathy? A systematic review.
To evaluate whether abnormal resistive index or cerebral blood flow velocity (CBFV) on cranial ultrasound predicts disability (≥1 year) in infants with hypoxic-ischaemic encephalopathy (HIE). This was a systematic review and meta-analysis of studies comparing developmental outcomes of infants with HIE with normal versus abnormal resistive index or CBFV. Twenty-six studies were included (pre-therapeutic hypothermia era, 20; therapeutic hypothermia era, six). Data from 15 studies (pre-therapeutic hypothermia, 10; therapeutic hypothermia, five) were available for meta-analysis. Pooled sensitivity and specificity, summary area under the receiver operating characteristic curve, and diagnostic odds ratio of resistive index or CBFV for predicting 'death or severe disability' were as follows. Pre-therapeutic hypothermia era: 0.83 (95% confidence interval [CI] 0.45-0.97) and 0.92 (95% CI 0.74-0.98), 0.94 (95% CI 0.92-0.96), 54 (95% CI 7-391). Therapeutic hypothermia era (measurements before therapeutic hypothermia): 0.62 (95% CI 0.41-0.80) and 0.96 (95% CI 0.88-0.99), 0.93 (95% CI 0.89-0.94), 23 (95% CI 6-91). Therapeutic hypothermia era (measurements during/after therapeutic hypothermia): 0.51 (95% CI 0.24-0.78) and 0.83 (95% CI 0.73-0.90), 0.81 (95% CI 0.78-0.85), 5 (95% CI 2-13). Overall Grading of Recommendations Assessment, Development and Evaluation (GRADE) rating of evidence was 'low' or 'very low'. Low-level evidence suggests that abnormal resistive index or CBFV can predict death or disability with high sensitivity and specificity in infants with HIE who are not cooled. The specificity of these tests was high when performed before starting cooling in infants who received therapeutic hypothermia. Cerebral doppler ultrasound may be useful in predicting death or disability in infants with hypoxic-ischaemic encephalopathy who are not cooled. Cerebral doppler ultrasound may also be useful in infants who are cooled, if done before starting cooling. Cerebral doppler ultrasound may not be useful when performed during or after completing cooling.


Changes in Device Uptake and Glycemic Control Among Pregnant Women With Type 1 Diabetes: Data From the T1D Exchange.
To examine changes in device use and glycemic outcomes for pregnant women from the T1D Exchange Clinic Registry between the years 2010-2013 and 2016-2018. Participant-reported device use and glycemic outcomes were compared for women aged 16-40 years who were pregnant at the time of survey completion, comparing 2010-2013 (cohort 1) and 2016-2018 (cohort 2). Hemoglobin A1c results within 30 days prior to survey completion were obtained from medical records. There were 208 pregnant women out of 5,236 eligible participants completing the questionnaire in cohort 1 and 47 pregnant women out of 2,818 eligible participants completing the questionaire in cohort 2. Continuous glucose monitor (CGM) use while pregnant trended upward among cohort 2 (70% vs 37%, P = .02), while reported continuous subcutaneous insulin infusion (CSII) use while pregnant declined (76% vs 64%, P = .04). HbA1c levels trended downward (6.8% cohort 1 vs 6.5% cohort 2, P = .07). Self-reported CGM use while pregnant increased over the studied intervals whereas CSII use decreased. Additional evaluation of device use and the potential benefits for T1D pregnancies is needed.


Enhanced Recovery After Surgery (ERAS) for Cranial Tumor Resection: A Review.
Enhanced Recovery After Surgery (ERAS) protocols describe a standardized method of preoperative, perioperative, and postoperative care to enhance outcomes and minimize complication risks surrounding elective surgical intervention. A growing body of evidence is being generated as we learn to apply principles of ERAS standardization to neurosurgical patients. First applied in spinal surgery, ERAS protocols have been extended to cranial neuro-oncologic procedures. This review synthesizes recent findings to generate evidence-based guidelines to manage neurosurgical oncology patients with standardized systems and assess ability of these systems to coordinate multidisciplinary, patient-centric care efforts. Furthermore, we highlight the potential usefulness of multimedia, app-based communication platforms to facilitate patient education, autonomy, and team communication within each of the 3 settings.


Pharmacotherapy in Conjunction with a Diet and Exercise Program for the Treatment of Weight Recidivism or Weight Loss Plateau Post-bariatric Surgery: a Retrospective Review.
Bariatric surgery is an effective therapeutic option for management of obesity. However, weight recidivism (WR) and weight loss plateau (WLP) are common problems. We present our experience with the use of two pharmacotherapies in conjunction with our standard diet and exercise program in those patients who experienced WR or WLP. From June 2010 to April 2014, bariatric surgery patients who experienced WR or WLP after undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), and who were treated with phentermine (Ph) or phentermine-topiramate (PhT), were reviewed retrospectively. Generalized estimating equations were used to compare patient weights through 90 days between initial surgery type and medication type. Patient weights, medication side effect, and co-morbidities were collected during the first 90 days of therapy. Fifty-two patients received Ph while 13 patients received PhT. Overall, patients in both groups lost weight. Among those whose weights were recorded at 90 days, patients on Ph lost 6.35 kg (12.8% excess weight loss (EWL); 95% confidence interval (CI) 4.25, 8.44) and those prescribed PhT lost 3.81 kg (12.9% EWL; CI 1.08, 6.54). Adjusting for baseline weight, time since surgery, and visit through 90 days, patients treated with Ph weighed significantly less than those on PhT throughout the course of this study (1.35 kg lighter; 95% CI 0.17, 2.53; p = 0.025). There were no serious side effects reported. Phentermine and phentermine-topirimate in addition to diet and exercise appear to be viable options for weight loss in post-RYGB and LAGB patients who experience WR or WLP.


Maternally perceived fetal activity from twenty-four weeks' gestation to term in normal and at risk pregnancies.
Maternal perception of fetal activity was studied in normal and at risk pregnancies from 24 weeks' gestation until term in the second and third hour after a maternal meal. The trend for the median number of maternally perceived fetal movements in the 2-hour observation period, across gestation, was similar to that previously reported in both maternally perceived and ultrasound studies. The median number of perceived fetal movements in any 15-minute interval was similar for both groups and was constant over gestational age. The periodicity of fetal activity perceived by mothers correlated well with ultrasonic observations. The data support that fetal movement counts are very variable. Periodicity must be taken into account when maternally perceived fetal activity is used as a screen of fetal well-being. The data suggest that the patient should be observed for a consecutive period, up to a maximum of 2 hours. If no fetal activity is perceived by 2 consecutive hours of observation, then further evaluation of fetal well-being should be considered.