Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions.
Cortical stimulation (CS) as a means to modulate regional activity and excitability in cortex is emerging as a promising approach for facilitating rehabilitative interventions after brain damage, including stroke. In this study, we investigated whether CS-induced functional improvements are linked with synaptic plasticity in peri-infarct cortex and vary with the severity of impairments. Adult rats that were proficient in skilled reaching received subtotal unilateral ischemic sensorimotor cortex (SMC) lesions and implantation of chronic epidural electrodes over remaining motor cortex. Based on the initial magnitude of reaching deficits, rats were divided into severely and moderately impaired subgroups. Beginning two weeks post-surgery, rats received 100 Hz cathodal CS at 50% of movement thresholds or no-stimulation control procedures (NoCS) during 18 days of rehabilitative training on a reaching task. Stereological electron microscopy methods were used to quantify axodendritic synapse subtypes in motor cortical layer V underlying the electrode. In moderately, but not severely impaired rats, CS significantly enhanced recovery of reaching success. Sensitive movement analyses revealed that CS partially normalized reaching movements in both impairment subgroups compared to NoCS. Additionally, both CS subgroups had significantly greater density of axodendritic synapses and moderately impaired CS rats had increases in presumed efficacious synapse subtypes (perforated and multiple synapses) in stimulated cortex compared to NoCS. Synaptic density was positively correlated with post-rehabilitation reaching success. In addition to providing further support that CS can promote functional recovery, these findings suggest that CS-induced functional improvements may be mediated by synaptic structural plasticity in stimulated cortex.


Practical Approach to Posttraumatic Intracranial Hypertension According to Pathophysiologic Reasoning.
Intracranial hypertension is one of leading causes of mortality after acute brain injury. Its causes and origins are multiple. The approach should be based on the underlying pathophysiology. There are different therapeutic modalities to control increased intracranial pressure (ICP), but all share the objective of normalizing basic physiologic variables. ICP control should be combined with adequate cerebral perfusion pressure. The classic approach to ICP control is unidirectional and sequential escalation of therapy. The nonresponse to classic therapy signaled a refractory condition. Multimodal monitoring has emerged as a useful tool, taking into account the analysis of ICP, oxygenation, and cerebral metabolism.


Psychometric properties of the Portuguese version of the Depressive Cognition Scale in Brazilian adults with diabetes mellitus.
Identifying depressive cognitions in Brazilians with diabetes can be important step to prevent the development of clinical depression, which is negatively associated with diabetes self-management. This study focused on the psychometric testing of the Portuguese version of the Depressive Cognition Scale, the Escala Cognitiva de Depressão (ECD), among 82 Brazilian adults with diabetes mellitus. The questionnaire was assessed for internal consistency, homogeneity, and construct validity using factor analysis and convergent validity assessment with the Portuguese version of the Beck Depression Inventory, the Inventário de Depressão Beck (IDB). Cronbach's alpha for the ECD was .88. The homogeneity of the instrument was supported by item-to-total correlations between .30 and .70. Factor extraction generated only one factor with eigenvalues greater than 1, which is consistent with the English version. The ECD's total score had a weak but significant correlation with the IDB's total score (r = .24, p < .05), indicating convergent validity. Evidence for the reliability and construct validity of the ECD was provided by this study. This scale has the potential to become a useful screening tool for depressive cognitions among Brazilians with diabetes.


[Clinical experience with ceftezole (author's transl)].
Ten patients with acute urinary tract infection or acute epididymitis were treated with ceftezole (CTZ) twice daily at a dose of 1 approximately 3 by intravenous injection. The effective ratio obtained was nearly 90%. As a side effect, exanthem was observed in one patient.


Prevalence of hematozoans in lions (Panthera leo) and cheetah (Acinonyx jubatus) in Serengeti National Park and Ngorongoro Crater, Tanzania.
Lions (Panthera leo) and cheetah (Acinonyx jubatus) from the Serengeti National Park and Ngorongoro Crater Conservation Area, Tanzania were examined for the presence of blood protozoans. Twenty-eight percent of the lions were infected with Trypanosoma sp. and the prevalence of trypanosome infection varied significantly between adjacent habitats. All of the animals were infected with Hepatozoon sp. and a Theileria sp.-like piroplasm that was morphologically indistinguishable from Theileria felis.


The Effects of Systemic Coenzyme Q10 Treatment on Corneal Histology in Streptozocin-Induced Diabetic Rats.
This study investigate the histopathological changes and VEGF, IL-1β, and IL-6 immunoreactivities in cornea treated with Coenzyme Q10 (CoQ10) in a Streptozocin (STZ) induced diabetic rat model. A total of 20 male Wistar Albino rats including a group of STZ diabetic rats, diabetic rats treated with CoQ10, rats were given CoQ10 without being diabetic and a Control group were included the study. The groups were followed up for 2 months. Eye tissues were stained with Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), and immunohistochemical staining (IHC). The mean corneal thickness was found to be lower in the group with DM (126,62 ± 18,1) compared to the other groups. However, this decrease was found to be significant only in comparison with the control group (181,75 ± 13,87) (p = 0.000). In diabetic corneas, PAS positivity was observed in in Descemet's membrane (p = 0.021). Staining with VEGF, IL-1β, IL-6antibodies was found to be lower in the DM+CoQ10 group compared to the group with DM (p < 0.001, p < 0.001, p < 0.001). We observed that diabetes increases inflammation and tendency to angiogenesis in the corneal tissue, and CoQ10 treatment reduces the corneal thickness, inflammation, and tendency to angiogenesis caused by diabetes.


Sugar for the brain: the role of glucose in physiological and pathological brain function.
The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease.


Immunochemical approach for zearalenone-4-glucoside determination.
Zearalenone-4-β-D-glucopyranoside (zearalenone-4-glucoside) detection techniques, based on a combination of acidic or enzymatic hydrolysis of the masked mycotoxin to the parent form (i.e. zearalenone), and immunochemical determination of zearalenone-4-glucoside as a difference between the zearalenone concentration after and before cleavage of the glycosidic bond were developed. The limit of detection for zearalenone-4-glucoside, achieved for the enzyme linked immunosorbent assay, was 3 μg kg(-1); the cut-off level for the sum of zearalenone and zearalenone-4-glucoside determination by a qualitative gel-based immunoassay was 50 μg kg(-1). Trifluoromethanesulfonic acid was checked for acidic hydrolysis and resulted in approximately 70% of glycosidic bond cleavage in optimal conditions. Seven different glycoside hydrolases were tested during the design of the enzymatic hydrolysis technique. Enzymatic hydrolysis combined with enzyme linked immunosorbent assay and gel-based immunoassay determinations was applied for the determination of zearalenone-4-glucoside or the sum of zearalenone and zearalenone-4-glucoside in cereal samples. The chosen enzyme (glucosidase from Aspergillus niger) allowed to cleave 102% of zearalenone-4-glucoside in standard solutions and 85% in cereal samples. Liquid chromatography coupled to tandem mass spectrometry was used as confirmatory method. As a result, good correlations between immunochemical techniques and the chromatographic data were obtained. The developed technique is suitable for simultaneous immunochemical determination of zearalenone and its masked form, zearalenone-4-glucoside.


Comparative photo-oxidative degradation of etodolac, febuxostat and imatinib mesylate by UV-C/H2O2 and UV-C/S2O82- processes: Modeling, treatment optimization and biodegradability enhancement.
The pharmaceutical contamination in aquatic environment has arisen increasing concern due to its potentially chronic toxicity. In recent years, HO° and SO4°- based advanced oxidation processes (AOPs) have been widely applied in water and wastewater treatments due to their highly efficiency on contaminant removal. Here, the response surface modeling (RSM) was used to investigate the degradation of three typical pharmaceuticals (i.e., etodolac (ETD), febuxostat (FBU) and imatinib mesylate (IMT)) by UV/H2O2 and UV/S2O82- processes. Based on the multiple regression analysis on full factorial design matrix and calculated reaction rate constants, the RSM was built. The experimental rate constants under optimal conditions were quite close to those obtained from the model, implying the good fit of the RSM. In addition, the RSM results indicated that UV/S2O82- process was less sensitive to pH in comparison to the UV/H2O2 process on target contaminant removal. Finally, it showed that UV/S2O82- process was superior to the UV/H2O2 process to on the enhancement of target contaminant biodegradability.


Characterization of new resistance plasmids belonging to incompatibility group IncQ.
New IncQ R plasmids, pIE639 and pIE723, are characterized and compared to the prototype IncQ plasmid RSF1010. Additional resistance determinants not common on other R plasmids are located on small stretches of DNA interspacing essential regions at different positions in an otherwise unchanged core of IncQ plasmid DNA. The contribution of IncQ plasmids to resistance evolution in bacteria is discussed.


Differential Etv2 threshold requirement for endothelial and erythropoietic development.
Endothelial and erythropoietic lineages arise from a common developmental progenitor. Etv2 is a master transcriptional regulator required for the development of both lineages. However, the mechanisms through which Etv2 initiates the gene-regulatory networks (GRNs) for endothelial and erythropoietic specification and how the two GRNs diverge downstream of Etv2 remain incompletely understood. Here, by analyzing a hypomorphic Etv2 mutant, we demonstrate different threshold requirements for initiation of the downstream GRNs for endothelial and erythropoietic development. We show that Etv2 functions directly in a coherent feedforward transcriptional network for vascular endothelial development, and a low level of Etv2 expression is sufficient to induce and sustain the endothelial GRN. In contrast, Etv2 induces the erythropoietic GRN indirectly via activation of Tal1, which requires a significantly higher threshold of Etv2 to initiate and sustain erythropoietic development. These results provide important mechanistic insight into the divergence of the endothelial and erythropoietic lineages.


Facilitating retroflexed endoscopic full-thickness resection through loop-mediated or rope-mediated countertraction (with videos).
Endoscopic full-thickness resection (EFTR) is difficult to perform in a retroflexed fashion in the gastric fundus and lesser curvature. Here we describe two simple methods to provide countertraction and thereby facilitate dissection. In this retrospective cohort study, 62 patients diagnosed as having gastric submucosal tumors in the fundus or in the lesser curvature received EFTR with or without countertraction methods. For the clip-with-thread method, a clip tied with surgical suture was anchored on the distal edge of the tumor to provide countertraction; for the loop-assisted method, a snare placed on the transparent cap beforehand was adopted to grasp the tumor to provide countertraction. Mean operative time was significantly reduced in the thread-with-clip group and loop-assisted group (45 minutes, 40 minutes, respectively) compared with the time needed in the traditional EFTR group (85 minutes). Intraoperative pneumoperitoneum occurred regularly among the 3 groups because of iatrogenic perforation, but fewer patients in the thread-with-clip group and loop-assisted group (23%, 18%, respectively) needed abdominal puncture to relieve free air and stabilize life signs compared with patients in the traditional EFTR group (63%). A reduced occurrence of high fever after surgery may contribute as another advantage from accelerated dissection. Both techniques did not jeopardize oncologic safety during short-term follow-up. Both the thread-with-clip method and loop-assisted method provide effective countertraction and offer faster and safer gastric EFTR in difficult anatomic locations.


A class of kernel based real-time elastography algorithms.
In this paper, a novel real-time kernel-based and gradient-based Phase Root Seeking (PRS) algorithm for ultrasound elastography is proposed. The signal-to-noise ratio of the strain image resulting from this method is improved by minimizing the cross-correlation discrepancy between the pre- and post-compression radio frequency signals with an adaptive temporal stretching method and employing built-in smoothing through an exponentially weighted neighborhood kernel in the displacement calculation. Unlike conventional PRS algorithms, displacement due to tissue compression is estimated from the root of the weighted average of the zero-lag cross-correlation phases of the pair of corresponding analytic pre- and post-compression windows in the neighborhood kernel. In addition to the proposed one, the other time- and frequency-domain elastography algorithms (Ara et al., 2013; Hussain et al., 2012; Hasan et al., 2012) proposed by our group are also implemented in real-time using Java where the computations are serially executed or parallely executed in multiple processors with efficient memory management. Simulation results using finite element modeling simulation phantom show that the proposed method significantly improves the strain image quality in terms of elastographic signal-to-noise ratio (SNRe), elastographic contrast-to-noise ratio (CNRe) and mean structural similarity (MSSIM) for strains as high as 4% as compared to other reported techniques in the literature. Strain images obtained for the experimental phantom as well as in vivo breast data of malignant or benign masses also show the efficacy of our proposed method over the other reported techniques in the literature.


Imatinib induces H2AX phosphorylation and apoptosis in chronic myelogenous leukemia cells in vitro via caspase-3/Mst1 pathway.
Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142) is required for tumor cell apoptosis. The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro. BCR-ABL-positive K562 cells were used. Microscopy, Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms. Treatment of K562 cells with imatinib (1-8 μmol/L) induced phosphorylation of H2AX at Ser139 and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX maintained a higher level in the cells. Meanwhile, imatinib (1-8 μmol/L) activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1), and induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD (40 μmol/L) reduced imatinib-induced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells. Imatinib (4 μmol/L) induced expression of Williams-Beuren syndrome transcription factor (WSTF), but not wild-type p53-induced phosphatase 1 (Wip1) in K562 cells. The caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.


Relationship of maternal factors and obstetric complications with term singleton vs term twin neonatal outcomes: A retrospective study in China.
Neonatal birth weight and length are important indicators of neonatal survival and morbidity during later life and are influenced by maternal factors and obstetrical complications. Therefore, we aimed to determine the relationship of maternal factors and obstetric complications with term singleton vs term twin neonatal outcomes in Wuhan University Renmin Hospital, Hubei, China. A total of 10517 neonatal births were recorded in a tertiary-hospital-based retrospective study and term singleton (n=7787) and term twins (n=169) were included for data analysis. Birth weight and birth length were measured immediately after birth. Correlation, independent student t-test, and backward multiple linear regression were used for statistical analysis. Women with singleton gestation have an increased rate of obstetric complications compared to women with twin gestation. However, a higher frequency of cesarean section and breech were found in twin gestation compared to singleton gestation. Weight before pregnancy, gestational weight gain, and gestational diabetes mellitus were significantly positive (p<0.05) associated with singleton neonatal birth length and weight. In contrast, preeclampsia, placenta previa, oligohydramnios, premature rupture of membrane, breech, and multiparity had a significantly negative (p<0.05) association with singleton neonatal birth length and weight. Maternal age was significantly positive (p<0.05) associated with only singleton neonatal birth weight. Moreover, the nuchal cord was significantly positive (p<0.05) associated with singleton neonatal birth length. On the other hand, maternal age and multiparity were significantly positive (p<0.05) associated with twins' neonatal birth length and weight. Furthermore, gestational weight gain was significantly positive (p<0.05) associated with only twins' neonatal birth weight. In term gestation, obstetric complications were significantly associated with singleton birth size rather than twin birth size.


Identification of low abundance microbiome in clinical samples using whole genome sequencing.
Identifying the microbiome composition from primary tissues directly affords an opportunity to study the causative relationships between the host microbiome and disease. However, this is challenging due the low abundance of microbial DNA relative to the host. We present a systematic evaluation of microbiome profiling directly from endoscopic biopsies by whole genome sequencing. We compared our methods with other approaches on datasets with previously identified microbial composition. We applied this approach to identify the microbiome from 27 stomach biopsies, and validated the presence of Helicobacter pylori by quantitative PCR. Finally, we profiled the microbial composition in The Cancer Genome Atlas gastric adenocarcinoma cohort.


TheAmerican Headache Society: looking back.
Dr. Kunkel, a former president and member of the American Headache Society from its most formative days, shares some personal recollections about the emergence of the society from a small group of like-minded individuals through to its period of rapid growth in the late 1970s and 1980s.


Chronic anal fissure.
The treatment of chronic anal fissure has shifted in recent years from surgical to medical. A Medline search of studies relevant to modern management of chronic anal fissure was undertaken. Traditional surgery that permanently weakens the internal sphincter is associated with a risk of incontinence. Medical therapies temporarily relax the internal sphincter and pose no such danger, but their limited efficacy has led to displacement rather than replacement of traditional surgery. Emerging medical therapies promise continued improvement and new sphincter-sparing surgery may render traditional surgery redundant. First-line use of medical therapy cures most chronic anal fissures cheaply and conveniently. The few non-responders can be targeted for sphincter assessment before traditional surgery. If the initial good results of new sphincter-sparing surgery are confirmed, it may be possible to avoid any risk of incontinence, while achieving high rates of fissure healing.


Comparative Evaluation of the Impact of Subacute Exposure of Smokeless Tobacco and Tobacco Smoke on Rat Testis.
This study investigated the effects of 30-day exposure to tobacco smoke (TS), smokeless tobacco (ST), and nicotine on reproductive parameters and oxidative biomarkers in prepubertal and adult male rats. Sperm motility was reduced by 77.5 and 89.0% in TS and ST exposed prepubertal rats and 71.1 and 86.4% in adult rats, respectively. Sperm count was also reduced by 64.7 and 89.9% in prepubertal rats and 64.9 and 47.0% in adult rats, respectively. Nicotine decreased sperm motility (82.2%) and count (62.6%) in prepubertal rats but caused no effect in adult rats. There were no changes in sperm morphology; testosterone was decreased, while LH and FSH were increased in exposed rats, when compared with control. Malondialdehyde levels in testes of exposed rats were increased, and GSH, SOD, and catalase were altered. Results indicate that subacute exposure of tobacco products alters sperm characteristics in a rank order of ST > TS > nicotine, which may be linked to increase in oxidative stress in the testis.


Intravenous cimetidine as an effective treatment for systemic anaphylaxis and acute allergic skin reactions.
Intravenous cimetidine treatment was prescribed for patients suffering from anaphylaxis, urticaria, pruritus, and contact dermatitis. Most of these patients recovered promptly from shock status, itching, and/or flushing after the administration of cimetidine. Intravenous cimetidine therefore may be an effective treatment for those allergic reactions.


Heat shock proteins and their expression in primary murine cardiac cell populations during ischemia and reperfusion.
A tight quality control system over protein folding, turnover and synthesis, involving molecular chaperones and co-chaperones, maintains the balance of cardiac proteins. Various cardiac pathologies, including myocardial infarction, increase stresses and post-translational modifications favoring misfolding due to an overwhelmed quality control system. The toxic nature of accumulated misfolded proteins further worsens the condition. The important molecular chaperones which act as quality control proteins are involved in protecting the heart, these include heat shock protein70 (HSP70) and HSP90. Here, we review the emerging roles of heat shock proteins in the maintenance of cardiac cell populations in experimental models of ischemia/reperfusion (I/R) injury. Furthermore, we discuss the expression of HSP70 and HSP90 with therapeutic and diagnostic considerations. Although there is only a partial understanding of these important HSPs in I/R injury, there is an immense therapeutic potential of modulating these HSPs to counteract the imbalance between misfolding and endogenous protein quality control systems.


Species barriers for chronic wasting disease by in vitro conversion of prion protein.
Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy that can affect North American cervids (deer, elk, and moose). Using a novel in vitro conversion system based on incubation of prions with normal brain homogenates, we now report that PrP(CWD) of elk can readily induce the conversion of normal cervid PrP (PrP(C)) molecules to a protease-resistant form, but is less efficient in converting the PrP(C) of other species, such as human, bovine, hamster, and mouse. However, when substrate brain homogenates are partially denatured by acidic conditions (pH 3.5), PrP(CWD)-induced conversion can be greatly enhanced in all species. Our results demonstrate that PrP(C) from cervids (including moose) can be efficiently converted to a protease-resistant form by incubation with elk CWD prions, presumably due to sequence and structural similarities between these species. Moreover, partial denaturation of substrate PrP(C) can apparently overcome the structural barriers between more distant species.


Recurrent CTNNB1 mutations in craniofacial osteomas.
Osteoma is a benign bone forming tumor predominantly arising on the surface of craniofacial bones. While the vast majority of osteomas develops sporadically, a small subset of cases is associated with Gardner syndrome, a phenotypic variant of familial adenomatous polyposis caused by mutations in the APC gene resulting in aberrant activation of WNT/β-catenin signaling. In a sequencing analysis on a cohort of sporadic, non-syndromal osteomas, we identified hotspot mutations in the CTNNB1 gene (encoding β-catenin) in 22 of 36 cases (61.1%), harbouring allelic frequencies ranging from 0.04 to 0.53, with the known S45P variant representing the most frequent alteration. Based on NanoString multiplex expression profiling performed in a subset of cases, CTNNB1-mutated osteomas segregated in a defined "WNT-cluster", substantiating functionality of CTNNB1 mutations which are associated with β-catenin stabilization. Our findings for the first time convincingly show that osteomas represent genetically-driven neoplasms and provide evidence that aberrant WNT/β-catenin signaling plays a fundamental role in their pathogenesis, in line with the well-known function of WNT/β-catenin in osteogenesis. Our study contributes to a better understanding of the molecular pathogenesis underlying osteoma development and establishes a helpful diagnostic molecular marker for morphologically challenging cases.


Effects of phenobarbital and tobacco smoking on furosemide kinetics and dynamics in normal subjects.
This study was carried out to determine whether furosemide (F) kinetics and dynamics were influenced by phenobarbital and tobacco smoking. Our subjects were 10 normal men: five nonsmokers (NS) and five smokers (S). They received a single intravenous F injection of 40 mg. Regular serum and urine collections were made. In a second study, the NS group received 100 mg phenobarbital orally for 15 days and then a second dose of F. Cumulative 8-hr urinary excretion of sodium was identical for NS, NS with phenobarbital, and S at 345 +/- 30, 357 +/- 29, and 353 +/- 25 mmol. Diuresis was smaller by 800 ml (20%) in S than in NS. F increased endogenous creatinine clearance from 117 +/- 13 to 196 +/- 17 ml/min in NS and from 110 +/- 12 to 222 +/- 30 ml/min in NS with phenobarbital. In the S group, endogenous creatinine clearance showed a tendency to increase only slightly, from 136 +/- 23 to 180 +/- 34 ml/min. The increase in free water clearance caused by F was smaller in the S group than in the NS group (P less than 0.05). Protein binding and distribution of F were not affected by phenobarbital or tobacco smoking. F clearance was slightly higher in S than in NS, which was primarily the result of a slight increase in extrarenal F clearance. In the NS group, F clearance remained constant after phenobarbital. It is concluded that tobacco smoking in normal subjects affects the diuretic response to F without modifying kinetics.


Preconcentration and determination of lead and cadmium levels in blood samples of adolescent workers consuming smokeless tobacco products in Pakistan.
The present study was aimed to evaluate the cadmium (Cd) and lead (Pb) levels in the blood samples of adolescent boys, chewing different smokeless tobacco (SLT) products in Pakistan. For comparative purpose, boys of the same age group (12-15 years), not consumed any SLT products were selected as referents. To determine trace levels of Cd and Pb in blood samples, a preconcentration method, vortex-assisted liquid-liquid microextraction (VLLME) has been developed, prior to analysis by flame atomic absorption spectrometry. The hydrophobic chelates of Cd and Pb with ammonium pyrrolidinedithiocarbamate were extracted into the fine droplets of ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate, while nonionic surfactant, Triton X-114 was used as a dispersing medium. The main factors affecting the recoveries of Cd and Pb, such as concentration of APDC, centrifugation time, volume of IL and TX-114, were investigated in detail. It was also observed that adolescent boys who consumed different SLT products have 2- to 3-fold higher levels of Cd and Pb in their blood samples as compared to referent boys (p < 0.001).


In-hospital outcomes following primary and revision total hip arthroplasty in nonagenarian patients.
The primary goal of this study was to assess the risk of postoperative surgical and medical complications and problems among nonagenarian patients operated with hip arthroplasty. Data from a specific high-volume arthroplasty clinic, were collected to evaluate postoperative morbidity and complication rates after hip arthroplasty in nonagenarians, compared with a control group of younger, but similar patients. Outcomes evaluated included length of stay, transfusion rate, and postoperative medical and surgical complication rates. A total of 97 nonagenarian patients (mean age 91.4 years) were included, and compared with 89 control group patients (mean age 70.18 years). Nonagenarian patients had significantly longer length of stay (11.44 vs. 7.98 days, p < 0.01), significantly higher risk of needing a transfusion (11.30% vs. 3.40%, p = 0.04), and significantly higher risk of a postoperative medical complication (28.90% vs. 11.20%, p = 0.03). There was no difference in postoperative surgical complication rate (7.20% vs. 2.20%, p = 0.12). Nonagenarian patients, when compared to a younger control group, experience significantly longer hospital stays, and risk of non-surgical complications. Arthroplasty in nonagenarian patients carries with it a high risk of complications, and thus careful pre-operative evaluation and the care of these patients at high volume, specialized clinics is important to optimize outcomes. Level III retrospective cohort analysis.


Echocardiographic results after repair of incompetent bicuspid aortic valves.
Valve-related complications and the necessity of anticoagulation after aortic valve replacement have led to new operative techniques for correction of aortic insufficiency (AI). Fourteen patients with bicuspid aortic valves and significant AI underwent valve repair. Transthoracic echocardiography was performed preoperatively and 1 week postoperatively and in 10 patients who have come to follow-up so far. Operative procedures were triangular resection of one leaflet in all patients. Five patients had pericardial patch plasty in addition. Mean AI decreased significantly from grade 3.5 +/- 0.1 preoperatively to 0.5 +/- 0.1 postoperatively (p < 0.001). Postoperatively, 10 patients had no or trivial AI (0 to 0.5), and 2 patients had mild AI (1 to 1.5). Within the first week, 2 patients were reoperated on after echocardiography established significant AI. Ventricular dimensions decreased from preoperative to postoperative and were normal after 1 year. At follow-up, 7 patients show no change of AI; in 3 patients AI increased to moderate because of dilatation of the sinus of Valsalva or the sinotubular junction. Reconstruction of bicuspid aortic valves is feasible with good early results. Echocardiography shows that asymmetric sinuses may lead to early perioperative failures and postoperative dilatation of the proximal aorta to increasing AI. Operative techniques may have to consider the pathology of the proximal aorta.


Efficacy and safety of a fixed combination of irbesartan/hydrochlorothiazide in Chinese patients with moderate to severe hypertension.
In a multi-center, single-arm, prospective study, we investigated the efficacy and safety of the fixed irbesartan/hydrochlorothiazide combination in Chinese patients with moderate to severe hypertension. Eligible patients were aged 18-75 years, with a blood pressure of 160-199 mmHg systolic or 100-119 mmHg diastolic during a 1-week wash-out phase off antihypertensive medication. The enrolled patients started antihypertensive treatment with irbesartan/hydrochlorothiazide 150 mg/12.5 mg once daily, with the possible addition of irbesartan 150 mg once daily and up-titration to irbesartan/hydrochlorothiazide 300 mg/25 mg once daily at 4 and 8 weeks of follow-up, respectively. The primary efficacy variable was the goal blood pressure-attaining rate at 12 weeks of follow-up (<140/90 mmHg, or <130/80 mmHg in patients with diabetes mellitus). In the intention-to-treat analysis (n = 501) at 12 weeks of follow-up, the goal blood pressure-attaining rate was 57.3%, and the mean change in blood pressure from baseline was 27.8 mmHg [95% confidence interval (CI) 26.4-29.1 mmHg; p < 0.001] systolic and 13.5 mmHg (95% CI 12.6-14.4 mmHg; p < 0.001) diastolic. Similar findings were observed in the per-protocol analysis (n = 449). The prevalence of microalbuminuria and left ventricular hypertrophy significantly (p ≤ 0.01) decreased from 33.4% (150/449) and 50.4% (215/427) at baseline to 23.4% (105/447) and 41.3% (176/427) at the end of follow-up, respectively. Four patients (2.0%) reported a serious adverse event. The fixed irbesartan/hydrochlorothiazide combination may control blood pressure to the target level in about 60% of Chinese patients with moderate to severe hypertension, with an acceptable safety profile.


Arterial splenic calcifications in children with AIDS: two case reports.
Splenic calcifications in AIDS patients are usually round and result from infections with opportunistic pathogens such as Pneumocystis carinii, Mycobacterium avium-intracellulare and Cytomegalovirus. We describe here a remarkable echopattern of the spleen in two pediatric patients, resulting from linear, branching calcifications in the splenic parenchymal arteries. We believe this echopattern represents the ultrasonographic manifestation of an HIV-associated vasculopathy.


Agonist-receptor efficacy. I: Mechanisms of efficacy and receptor promiscuity.
The description of drug effects on receptor proteins is based on models and equations used to describe mass-action kinetics of molecules and inert surfaces. These models provide an adequate description of drug affinity, that is, how well a molecule binds to a receptor protein, but the way in which ligands change receptor populations to impart signals to cells remains to be determined. In the first of two articles, Terry Kenakin discusses a basic question in receptor pharmacology, namely the nature of ligand efficacy.


Use of bone graft substitutes and bioactive materials in treatment of distal radius fractures.
Although autogenous bone graft has been shown to be useful in the treatment of distal radius fractures, the role of bone graft substitutes and the optimal replacement material remains unclear. Several products are commercially available, each with differing osteoconductive, osteoinductive, and structural properties. Indications and choice of graft substitute should be based on the needs of the individual case with regard to need for structural support, gap filling, or bone healing stimulation. Further comparative research will help clarify the indications and most appropriate material for a given fracture and clinical situation.


The fate of biodegradable microspheres injected into rat brain.
Biodegradable microspheres made with poly-[D,L-lactide-co-glycolide] represent an evolving technology for drug delivery into the central nervous system. Even though these microspheres have been shown to be engulfed by astrocytes in vitro, the purpose of the present study was to track the fate of biodegradable microspheres in vivo. This was accomplished using microspheres containing the fluorescent dye coumarin-6 followed 1 day, 1 week and 1 month after intracerebral injections of this material were made into the rat brain. Using dual color immunohistochemistry and antisera against glial fibrillary acidic protein for astrocytes versus phosphotyrosine for microglia, results demonstrate that phagocytosis of small coumarin-containing microspheres <7.5 microm in diameter was primarily by microglia in vivo during the first week post-injection. In contrast, only a small minority of these microspheres appeared to be engulfed by astrocytes.


The effects of maternal smoking on pregnancy outcome and placental histopathology lesions.
To study the effects of maternal smoking on pregnancy outcome and placental histopathology findings. Maternal and labor characteristics and pathological reports were compared between term placentas of complicated and uncomplicated pregnancies of: heavy smokers (>10 cigarettes per day, H-smokers), moderate smokers (<10 cigarettes per day, M-smokers) and non-smokers (controls, N-smokers). Birth-weights were lower in the H-smokers and M-smokers as compared to the N-smokers (p<0.001), with a higher rate of small for gestational age (SGA): 18.2%, 19.2% and 11.4%, respectively (p=0.01). Deliveries among smokers were characterized by higher rates of abnormal fetal heart rate tracings during labor as compared to non-smokers (p=0.01). Rates of placental maternal and fetal stromal-vascular supply lesions was similar between the groups. Maternal smoking is associated with higher rates of SGA. Tobacco's potential influence is probably through the disruption of normal placental epigenetic patterns, not expressed in placental histopathology lesions.


The ulnar side of the wrist: Clinically relevant anatomy and biomechanics.
In the hectic environment of a hand therapy clinic, the opportunity to carefully consider the relationships among pathology, pathomechanics, surgical repair techniques, tissue healing, postoperative management, and rehabilitation program development and progression is limited. Clinicians often default to seeking a protocol, a recipe to follow. Using the ulnar side of the wrist as an example, relevant anatomy and biomechanics are directly related to several commonly seen pathologies, including fractures, ligament injuries, and instability. Armed with knowledge of anatomy, biomechanics, and surgical procedures, the need for a protocol disappears. Each patient can be individually managed according to his or her unique set of variables and responses to injury, repair, healing, and recovery of function.


Effectiveness comparison of endoscopic methods of non-varicose upper gastrointestinal bleeding treatment.
In every case of upper gastrointestinal bleeding suspicion, an endoscopic examination ought to be performed as a matter of urgency. Finding active bleeding, a visible non-bleeding vessel or a lesion with an adherent clot should be followed by application of an available method of endoscopic therapy. The aim of the study was to compare the effectiveness of various endoscopic treatment techniques such as epinephrine injections, coagulation methods and mechanical methods in the treatment of non-varicose upper gastrointestinal bleeding. Sixty cases of non-varicose upper gastrointestinal bleeding were analysed in terms of the effectiveness of the above-mentioned procedures used in monotherapy or in combination therapy comprising epinephrine injections and clips application. The choice of the applied procedure depended on morphological features and location of the bleeding source, the patient's general condition, as well as technical equipment and manual skills of the endoscopy staff. The study confirmed the effectiveness of endoscopic treatment of non-varicose upper gastrointestinal bleeding applying the above-mentioned methods. In most patients, this treatment enabled traumatic surgical intervention to be avoided; it was required in only 3 (5%) out of 60 patients with confirmed upper gastrointestinal bleeding. With the first endoscopy, haemostasis was achieved in 47 cases (78.3%) and the second endoscopy, performed due to bleeding recurrence, was successful in the remaining 10 cases (16.7%). In non-varicose upper gastrointestinal bleeding, urgent diagnostic and therapeutic endoscopy should be the first-line management. If the lesion that is the source of bleeding is possible to localize, the endoscopic techniques should be applied. Among the endoscopic procedures used in monotherapy, clips appeared to be the most effective, their effectiveness being comparable to combination therapy. In bleeding from extensive lesions, coagulation methods are considered to be the most efficacious.


Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways.
Due to the cytotoxicity of 4-hydroxynonenal (HNE), and to the fact that this major product of lipid peroxidation is a rather long-living compound compared with reactive oxygen species, the capability of organisms to inactivate and eliminate HNE has received increasing attention during the last decade. Several recent in vivo studies have addressed the issue of the diffusion, kinetics, biotransformation and excretion of HNE. Part of these studies are primarily concerned with the toxicological significance of HNE biotransformation and more precisely with the metabolic pathways by which HNE is inactivated and eliminated. The other aim of in vivo metabolic study is the characterisation of end-metabolites, especially in urine, in order to develop specific and non-invasive biomarkers of lipid peroxidation. When HNE is administered intravenously or intraperitoneally, it is mainly excreted into urine and bile as conjugated metabolites, in a proportion that is dependent on the administration route. However, biliary metabolites undergo an enterohepatic cycle that limits the final excretion of faecal metabolites. Only a very low amount of metabolites is found to be bound to macromolecules. The main urinary metabolites are represented by two groups of compounds. One comes from the mercapturic acid formation from (i) 1,4 dihydroxynonene-glutathione (DHN-GSH) which originates from the conjugation of HNE with GSH by glutathione-S-transferases and the subsequent reduction of the aldehyde by a member of aldo-keto reductase superfamily; (ii) the lactone of 4-hydroxynonanoic-GSH (HNA-lactone-GSH) which originates from the conjugation of HNE followed by the oxidation of the aldehyde by aldehyde dehydrogenase; (iii) HNA-GSH which originates from the hydrolysis of the corresponding lactone. The other one is a group of metabolites issuing from the omega-hydroxylation of HNA or HNA-lactone by cytochromes P450 4A, followed eventually, in the case of omega-oxidized-HNA-lactone, by conjugation with GSH and subsequent mercapturic acid formation. Biliary metabolites are GSH or mercapturic acid conjugates of DHN, HNE and HNA. Stereochemical aspects of HNE metabolism are also discussed.


Deep learning in target prediction and drug repositioning: Recent advances and challenges.
Drug repositioning is an attractive strategy for discovering new therapeutic uses for approved or investigational drugs, with potentially shorter development timelines and lower development costs. Various computational methods have been used in drug repositioning, promoting the efficiency and success rates of this approach. Recently, deep learning (DL) has attracted wide attention for its potential in target prediction and drug repositioning. Here, we provide an overview of the basic principles of commonly used DL architectures and their applications in target prediction and drug repositioning, and discuss possible ways of dealing with current challenges to help achieve its expected potential for drug repositioning.


Single-session radiofrequency tongue base reduction combined with uvulopalatopharyngoplasty for obstructive sleep apnea syndrome.
This study aimed to evaluate the efficacy and safety of single-session radiofrequency tongue base reduction (RTBR) combined with uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea syndrome (OSAS). Sixty-six patients with multilevel obstruction underwent single-session RTBR combined with UPPP. Snoring, Epworth sleepiness scale (ESS) and polysomnography were used to assess outcome before and 6 months after treatment. Sixty-six patients completed this study. Snoring level significantly decreased from 8.0 to 4.3. The mean ESS score significantly decreased from 11.4 to 7.5. The mean apnea-hypopnea index decreased significantly from 22.9 to 13.9. The overall success rate of the single-session RTBR combined with UPPP was 53.6%. Postoperative AHI in 50% of patients was normalized (AHI < 5). The success rates for patients with mild, moderate and severe OSAS were 62.5, 46.2 and 57.1%, respectively. There were two adverse effects, one ulceration of the tongue base and one transient taste change. Single-session RTBR combined with UPPP is an effective and safe treatment for OSAS patients with multilevel obstruction. It could be considered as first treatment for OSAS patients with multilevel obstruction, independent of the severity of OSAS.


Age and antihypertensive drugs (hydrochlorothiazide, bendroflumethiazide, nadolol and captopril).
Three double-blind Veterans Administration Cooperative Studies are reviewed to determine age-related changes in response to antihypertensive agents. In the first study 312 patients received hydrochlorothiazide titrated from 25 to 100 mg twice daily to lower diastolic blood pressure (BP) to less than 90 mm Hg. Of 121 patients aged 55 to 65 the decrease in BP averaged -21.8/-12.9 mm Hg, while in the 191 patients younger than 55 the reduction averaged -15.7/-11.5 mm Hg (p less than 0.001; p = 0.048, respectively). Both systolic and diastolic BP reductions averaged significantly more in older whites; in older blacks it was systolic BP only. An additional 298 patients received titrated doses of propranolol alone. In this group there were no significant differences in BP response between younger patients and patients aged 55 to 65 except in the subgroup of white patients older than 60, in whom the systolic reduction was significantly less than in the younger patients. In a second study of bendroflumethiazide alone and with nadolol, systolic BP decreased more in older than in younger patients but there was no age-related reduction with nadolol alone. In the third trial captopril was first given alone and later with hydrochlorothiazide. There were no age-related differences with captopril alone, but after the addition of hydrochlorothiazide there was a trend toward a greater antihypertensive response in the patients aged 55 to 69. Thus, responsiveness of older patients varies with the type of antihypertensive drug. Age appears to increase the antihypertensive response to thiazide diuretics but not to beta-adrenergic blocking drugs or to captopril.


High-Level Systematic Ab Initio Comparison of Carbon- and Silicon-Centered SN2 Reactions.
We characterize the stationary points along the Walden inversion, front-side attack, and double-inversion pathways of the X- + CH3Y and X- + SiH3Y [X, Y = F, Cl, Br, I] SN2 reactions using chemically accurate CCSD(T)-F12b/aug-cc-pVnZ [n = D, T, Q] levels of theory. At the carbon center, Walden inversion dominates and proceeds via prereaction (X-···H3CY) and postreaction (XCH3···Y-) ion-dipole wells separated by a usually submerged transition state (X-H3C-Y)-, front-side attack occurs over high barriers, double inversion is the lowest-energy retention pathway for X = F, and hydrogen- (F-···HCH2Y) and halogen-bonded (X-···YCH3) complexes exist in the entrance channel. At the silicon center, Walden inversion proceeds through a single minimum (X-SiH3-Y)-, the front-side attack is competitive via a usually submerged transition state separating pre- and postreaction minima having X-Si-Y angles close to 90°, double inversion occurs over positive, often high barriers, and hydrogen- and halogen-bonded complexes are not found. In addition to the SN2 channels (Y- + CH3X/SiH3X), we report reaction enthalpies for proton abstraction (HX + CH2Y-/SiH2Y-), hydride substitution (H- + CH2XY/SiH2XY), XH···Y- complex formation (XH···Y- + 1CH2/1SiH2), and halogen abstraction (XY + CH3-/SiH3- and XY- + CH3/SiH3).


Correction to: 2019 Neurocritical Care Survey: Physician Compensation, Unit Staffing and Structure.
The original article had a typo in Table 2, the "N" for males and females should be switched. The corrected table is shown below.


A retrospective study on the transition of radiation dose rate and iodine distribution in patients with I-131-treated well-differentiated thyroid cancer to improve bed control shorten isolation periods.
To evaluate for how long patients should be isolated after I-131 treatment for thyroid cancer according to the guidelines issued by the Japanese Ministry of Welfare. We reviewed 92 therapies performed in 76 patients who were administered I-131 at our hospital from July 2007 to September 2009. Fifty-six patients were given 2220 or 2960 MBq I-131 at the first therapy, and 29 patients underwent 36 repeated therapies using 2960, 3700, 5550 or 7400 MBq I-131. We surveyed radioactivity for a 1 cm dose equivalent rate at 1 m intervals at 30 and 48 h after administration of I-131, obtained planar scintigrams at 48 h, and surveyed radioactivity repeatedly until it fell to under 30 μSv/h. The radioactivity was under 30 μSv/h at 30 h in 51 out of 92 cases (55%). Among the remaining 41 (45%) cases, 27 (29%) and 32 (35%) cases showed decreased radioactivity under 30 μSv/h at 48 and 72 h, respectively, and it remained higher than 30 μSv/h at 72 h in another 9 cases (10%). In 5 (38%) of the 13 cases with bone metastasis, the radioactivity remained over 30 μSv/h after 72 h, and scintigrams showed strong accumulation in bone metastases. Among the 27 cases demonstrating below 30 μSv/h at 48 h, 26 showed radioactivity being below 50 μSv/h at 30 h, while it was above 50 μSv/h at 30 h in all 14 cases which demonstrated above 30 μSv/h at 48 h. We compared the radioactivity levels of 27 cases under 30 μSv/h at 48 h and 14 cases over 30 μSv/h at 48 h using a cutoff value of under 50 μSv/h at 30 h to release patient at 48 h, the positive predictive value and negative predictive value were 100 and 93%, respectively, and radioactivity was found to differ significantly (P < 0.001). To predict external radiation levels at 48 h, it is helpful to consider external radiation levels at 30 h after treatment. Consideration of intracellular uptake in thyroid cancer, especially in cases of bone metastases, digestive tract function, and renal function, is important for predicting isolated period.


Origin and turnover of ECM proteins from the inner limiting membrane and vitreous body.
The inner limiting membrane (ILM) and the vitreous body (VB) are two major extracellular matrix (ECM) structures that are essential for early eye development. The ILM is considered to be the basement membrane of the retinal neuroepithelium, yet in situ hybridization and chick/quail transplant experiments in organ-cultured eyes showed that all components critical for ILM assembly, such as laminin or collagen IV, are not synthesized by the retina. Rather, ILM proteins, with the exception of agrin, originate from the lens or (and) ciliary body and are shed into the vitreous. The VB serves as a reservoir providing high concentrations of ILM proteins for the instant assembly of new ILM during rapid embryonic eye growth. The function of the retina in ILM assembly is to provide the cellular receptor proteins for the binding of the ILM proteins from the vitreous. The VB is a gelatinous ECM structure that fills the vitreous cavity of the eye. Its major structural proteins, collagen II and fibrillin, originate primarily from the ciliary body. Reverse transcription-PCR and western blotting show that the rate of synthesis of structural, monomeric ILM and VB proteins, such as laminin, collagen IV and II is very high during embryogenesis and very low in the adult. The downregulation of ILM and VB protein synthesis occurs during early postnatal life, and both ILM and VB are from then on maintained throughout life with minimum turnover. Our data explain why ILM and VB do not regenerate after vitrectomy and ILM peeling.


The timing between REM sleep behavior disorder and Parkinson's disease.
In Parkinson's disease (PD) patients, REM sleep behavior disorder (RBD) might precede PD or develop with or after the onset of PD. No previous study has explored differences between these two groups. The aim of this study was therefore to compare clinical features and REM sleep chin electromyographic patterns between patients in whom RBD heralded PD and those in whom RBD occurrence coincided with or followed the clinical manifestations of PD. Twenty-seven consecutive PD patients (mean age 67.9 years) were enrolled. Detailed clinical, laboratory, and polysomnographic studies were obtained in all participants. Sixteen of the 27 patients were affected by RBD. These had a significantly higher stage of PD and took significantly higher doses of dopaminergic therapy; their disease duration tended to be longer, and their cognitive status tended to be lower. PD patients in whom RBD preceded PD (n = 6) did not differ from PD patients without RBD in disease parameters, while PD patients in whom RBD developed with or after PD (n = 10) showed a significantly higher disease stage, took significantly higher dopaminergic therapy, and had a longer disease duration. Our findings are compatible with the hypothesis that patients in whom RBD precedes, or does not precede, PD might constitute two possibly distinct clinical and physiopathological groups, based on different progressive neuropathological sequences of events.


In vitro effects of insulin on aldosterone production in rat zona glomerulosa cells.
Though long standing diabetes mellitus is frequently accompanied by hypoaldosteronism, the role of insulin in this setting has never been clearly established. In the present study we have examined the direct effects of insulin on aldosterone production in rat zona glomerulosa cells in vitro. Insulin is shown to directly stimulate aldosterone production in a dose dependent manner, and to attenuate angiotensin II mediated aldosterone production, without affecting angiotensin II receptor binding kinetics. Insulin had no effect on aldosterone production mediated by the other physiological stimuli (K+ and ACTH). These data suggest a possible interaction between insulin and angiotensin II in the regulation of aldosterone secretion.


Surgical management of upper lid epiblepharon.
Upper lid epiblepharon refers to a developmental anomaly characterised by the presence of an exaggerated skin fold running horizontally across the upper lid below the lid margin, which in severe cases is associated with lash-cornea touch or even corneal punctate epithelial erosions. This retrospective study looked at 14 patients who underwent bilateral upper lid pretarsal orbicularis debulking and skin excision to correct lash-globe contact from the upper lid. Surgery was successful in 25 of 28 lids, with one recurrence being successfully re-operated. The remaining 2 recurrences did not undergo further surgery as the patients were asymptomatic. This surgical procedure appears to be an effective treatment of lash inversion in upper lid epiblepharon with good aesthetic results.


Muscarinic cholinergic receptor binding and electrophysiological response to acetylcholine in cultured rat caudate putamen nucleus neurons.
Binding sites with specificity for N-[3H]methylscopolamine ([3H]NMS) are present in homogenates of primary culture neurons from the rat caudate putamen nucleus (CPN). Specific binding is saturable with respect to [3H]NMS. The Scatchard analysis indicates a dissociation constant of 0.6 nM and a density of 7.0 X 10(3) per cell, or 78 fmol/mg protein. In electrophysiological measurements, excitatory postsynaptic currents (EPSCs) in larger cells were increased by pressure application of acetylcholine under voltage clamp condition. The EPSCs may come from neighboring smaller cells with muscarinic acetylcholine receptors.


Models of inflammation: carrageenan air pouch.
The subcutaneous air pouch is an in vivo model that can be used to study acute and chronic inflammation, the resolution of the inflammatory response, and the oxidative stress response. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.


Clinically Important Misclassification of Aortic Valve Stenosis Severity Using Non-Invasive Techniques: Simultaneous Echocardiography and Cardiac Catheterization During Transcatheter Aortic Valve Implantation in Awake Patients.
Suitability for transcatheter aortic valve (AV) implantation (TAVI) is determined by using transthoracic echocardiography (TTE), although left-sided cardiac catheterization (LCC) provides directly measured pressure data. TAVI in awake patients permits simultaneous comparison of TTE and LCC under physiologically relevant left ventricular loading conditions. We hypothesized that clinically important discrepancies between TTE and LCC would be identified. TAVI was performed in 108 awake patients undergoing intra-procedural TTE and LCC between January 1, 2016 and December 31, 2016, based upon pre-procedure TTE data. Intra-procedural assessments simultaneously were performed before and after prosthesis implantation. Based upon mean trans-AV systolic ejection pressure gradient (MSEPG), AS was graded as: mild (<20 mm Hg; grade 1), moderate (20 - <40 mm Hg; grade 2), or severe (≥40 mm Hg; grade 3). In 79 of the 108 (73.1%) patients, intra-procedural TTE and LCC assessments were concordant. In 2 of the 108 (1.9%) patients, TTE overestimated AS severity by ≥1 grade. In 27 of the 108 (25.0%) patients, TTE underestimated AS severity by ≥1 grade. In total, AS severity reclassification occurred in 29 (26.9%) patients. Overall, TTE underestimated MSEPG by 8.9 ± 1.2 mm Hg (TTE MSEPG versus LCC MSEPG; P < .001). Current TTE criteria appear to frequently and importantly underestimate AS severity. Because decision-making regarding TAVI often exclusively is based upon TTE data, these findings suggest either a continued role for LCC in the diagnostic assessment of AS in patients who do not meet standard TTE criteria or lowering TTE cutoffs for TAVI.


Thymic stroma in AKR mice: its function and virus production.
This study reports experiments with thymic stromal remnants in AKR mice, a strain with a high natural incidence of thymic lymphoma. A method has been developed in which thymic stromal cells which survive a 4-week culture period, 1 week at 24 degrees C and 3 weeks at 37 degrees C are suitable for grafting. Most thymic lymphocytes die under these conditions. Stromal remnants were studied by culturing and grafting under the kidney capsule of 2-month-old syngeneic mice. Their in vitro morphology and virus production, their ability to reconstitute a new thymus from host progenitors and their eventual lymphoma development was evaluated. The stromal remnants were from: 1- and 3-month-old normal mice; 6-10-month-old normal mice; 21-28-day-old animals treated with the lymphomagenic virus, SL3-3, at 3 days of age. Our data show that thymic stromal function as measured by lymphoid reconstitution of thymic stromal grafts of AKR mice is not impaired with age or by the presence of oncogenic virus. Oncogenic viruses are found in the thymic stroma of old mice and in thymic stroma of young virus-treated mice. Oncogenic viruses are not found in thymic stroma of young normal mice. Lymphoma can develop in the grafted stromal remnants expressing lymphomagenic virus.


Methodology and application of prospective reader studies: self-assessment module.
The educational objectives of this self-assessment module are for the participant to read selected sources on prospective reader study methodologies and to self-assess and improve his or her knowledge of this subject.


The role of receptor internalization in CD95 signaling.
Activation of the cell surface CD95 receptor triggers a cascade of signaling events, including assembly of the death-inducing signaling complex (DISC), that culminate in cellular apoptosis. In this study, we demonstrate a general requirement of receptor internalization for CD95 ligand-mediated DISC amplification, caspase activation and apoptosis in type I cells. Recruitment of DISC components to the activated receptor predominantly occurs after the receptor has moved into an endosomal compartment and blockade of CD95 internalization impairs DISC formation and apoptosis. In contrast, CD95 ligand stimulation of cells unable to internalize CD95 results in activation of proliferative Erk and NF-kappaB signaling pathways. Hence, the subcellular localization and internalization pathways of CD95 play important roles in controlling activation of distinct signaling cascades to determine divergent cellular fates.


ANCUT2, an extracellular cutinase from Aspergillus nidulans induced by olive oil.
Cutinases are versatile carboxylic ester hydrolases with great potential in many biocatalytic processes, including biodiesel production. Genome sequence analysis of the model organism Aspergillus nidulans reveals four genes encoding putative cutinases. In this work, we purified and identified for the first time a cutinase (ANCUT2) produced by A. nidulans. ANCUT2 is a 29-kDa protein which consists of 255 amino acid residues. Comparison of the amino acid sequence of ANCUT2 with other microbial cutinase sequences revealed a high degree of homology with other fungal cutinases as well as new features, which include a serine-rich region and conserved cysteines. Cutinase production with different lipidic and carbon sources was also explored. Enzyme activity was induced by olive oil and some triacylglycerides and fatty acids, whereas it was repressed by glucose (1%) and other sugars. In some conditions, a 22-kDa post-translational processing product was also detected. The cutinase nature of the enzyme was confirmed after degradation of apple cutin.


Effect of multistage process on the quality, water and oil distribution and microstructure of French fries.
The production of French fries is a multistage process (blanching, pre-frying, freezing and final frying). Pre-stage processing can result in drastic changes related to the quality of the final product. In this study, we investigated the effect of multistage process on quality properties, water and oil distribution and microstructure of fries prepared with different oils. Results showed that freezing treatment had little effect on water and oil content, color and volumetric shrinkage of pre-fried fries. Final fried fries exhibited drastic changes involved in the content and status of water and oil, color, texture, volumetric shrinkage and microstructure compared with other processing stage. Besides, magnetic resonance imaging visualized a thicker crust in finish-fried fries. Among all the oils, fries fried in high-oleic sunflower oil showed the best mouthfeel. This will provide a theoretical guidance for food enterprise to produce high-quality French fries.


Description and rules of a new card game to learn clinical reasoning in musculoskeletal physiotherapy.
Teaching hypothetico-deductive clinical reasoning (CR) should be an essential part of the physiotherapy education system, but currently there are very few learning tools for teachers in the musculoskeletal discipline. The aim of this article was to describe and present the rules of a new game-based and structured didactic tool that can be used by teachers for 'players' (students and licensed clinicians) to learn systematic CR in musculoskeletal physiotherapy.Our tool is based on the 'Happy Families' card game, and we propose to use it as part of a classic musculoskeletal subjective examination-based hypothesis category framework and the International Classification of Functioning, Disability and Health model. It allows players to dynamically formulate hypotheses from clinical case studies. Each 'Family' of cards represents a hypothesis category. The game highlights the missing information and trains players to consider it in their CR.This game should efficiently structure all components of CR and is an interesting resource for all teachers. Its greatest strength is that it can be used with other category frameworks. Further studies are needed to assess the efficacy and efficiency of such a tool and to measure students' actual progress in learning the CR.


In vivo reverse total shoulder arthroplasty contact mechanics.
Several in vitro studies have investigated the biomechanics of reverse total shoulder arthroplasty (RTSA); however, few in vivo studies exist. The purpose of this study was to examine in vivo RTSA contact mechanics in clinically relevant arm positions. Our hypothesis was that contact would preferentially occur in the inferior region of the polyethylene liner. Forty patients receiving a primary RTSA were recruited for a prospective cohort study. All patients received the same implant design with a nonretentive liner. Stereo radiographs were taken at maximal active range of motion. Model-based radiostereometric analysis was used to identify implant position. Contact area between the polyethylene and glenosphere was measured as the geometric intersection of the 2 components and compared with respect to polyethylene liner size, arm position, and relative position within the liner. There were no differences in the proportion of contact area in any arm position between polyethylene liner sizes, ranging from 30% ± 17% to 38% ± 23% for 36-mm liners and 32% ± 21% to 41% ± 25% for 42-mm liners. Contact was equally distributed between the superior and inferior halves of the liner at each arm position (P = .06-.79); however, greater contact area was observed in the outer radius of the liner when the arm was flexed (P = .002). This study highlights that contact mechanics are similar between 36- and 42-mm liners. Contact area is generally equally distributed throughout the liner across the range of motion and not preferentially in the inferior region as hypothesized.


Ultrasonic sensor based defect detection and characterisation of ceramics.
Ceramic tiles, used in body armour systems, are currently inspected visually offline using an X-ray technique that is both time consuming and very expensive. The aim of this research is to develop a methodology to detect, locate and classify various manufacturing defects in Reaction Sintered Silicon Carbide (RSSC) ceramic tiles, using an ultrasonic sensing technique. Defects such as free silicon, un-sintered silicon carbide material and conventional porosity are often difficult to detect using conventional X-radiography. An alternative inspection system was developed to detect defects in ceramic components using an Artificial Neural Network (ANN) based signal processing technique. The inspection methodology proposed focuses on pre-processing of signals, de-noising, wavelet decomposition, feature extraction and post-processing of the signals for classification purposes. This research contributes to developing an on-line inspection system that would be far more cost effective than present methods and, moreover, assist manufacturers in checking the location of high density areas, defects and enable real time quality control, including the implementation of accept/reject criteria.


In vitro synthesis, release and uptake of storage proteins by the fat body of Manduca sexta: putative hormonal control.
1. Two major proteins (P1 and P2) are synthesized by the fifth instar larval fat body of Manduca sexta and then released into the hemolymph. 2. These proteins are later sequestered by the pre-pupal fat body. 20-Hydroxyecdysone does not appear to affect the synthesis of either protein. 3. When day 2 fifth instar larvae are neck-ligated there is an excessive synthesis (supersynthesis) of P2 (arylphorin). 4. Juvenile hormone I (JH I) applications to ligated animals had no effect, but brain homogenate injections resulted in the inhibition of P2 synthesis. 5. Neck ligations of larvae between days 5 and 6 revealed a head critical period between day 5 + 12 hr and day 5 + 18 hr, after which the head is unnecessary for the sequestration of either protein by the fat body. 6. JH I and JH III applications to ligated larvae before the head critical period do not restore the ability of the fat body to sequester the storage proteins. 7. P1 and P2 appear to be synthesized differentially and P2 is sequestered by the fat body to a much lesser extent than P1. 8. P2 is the hemolymph storage protein of both larval and pupal stages, whereas P1 appears to be the storage protein of the pupal fat body. 9. The data indicate that the synthesis of arylphorin and the resorption of both proteins are controlled by a putative head factor(s).


WNT6 is a novel target gene of caveolin-1 promoting chemoresistance to epirubicin in human gastric cancer cells.
Resistance to chemotherapy is a major obstacle for curative treatment of human gastric cancer (GC). However, the underlying molecular mechanisms are largely unknown. Wingless-type MMTV integration site family members (WNTs) are secreted glycoproteins involved in embryogenesis and, on inappropriate expression in the adult, in cancer. Here, we show expression of WNT6 in GC patient specimens, human GC cell lines and in a mouse model of GC. In human GC cells, WNT6 expression was enhanced by caveolin-1 (Cav1), a scaffold protein of plasma membrane caveolae. WNT6 knock-down and overexpression experiments demonstrated that WNT6 increased the resistance to apoptotic cell death induced by the anthracycline chemotherapeutics epirubicin (Epi) and doxorubicin (Dox). Epi increased the activity of the human WNT6 promoter through Cav1-dependent binding of β-catenin to the proximal WNT6 promoter. Epi increased both WNT6/Wnt6 and Cav1 expression in human GC cells and within the tumor area of a murine model of GC (CEA424-SV40 TAg). In GC patients, WNT6 expression was positively associated with the tumor stage and the nodal status, and inversely correlated with the response to ECF (Epi, cisplatin, 5-fluorouracil) chemotherapy. These results showed that WNT6 and Cav1 are upregulated by chemotherapeutics and enhance the resistance of GC cells to anthracycline drugs. Understanding the molecular mechanisms driving WNT6/Cav1-induced drug resistance will provide benefits in developing new therapies for GC.


Neuropathic Pain Among Community-Dwelling Older People: A Clinical Study in Finland.
Neuropathic pain is more common among older people than in the general population, and the efficacy of medical treatment often remains unsatisfactory. The aim of this study was to assess the presence, diagnostic certainty, etiology and treatment of neuropathic pain in community-dwelling older people with chronic pain. Independently living older people aged 75, 80 and 85 years subject to communal preventive home visits with chronic pain were invited to a clinical pain examination by a geriatrician. Overall, 106 patients consented to participate in the clinical study. Neuropathic pain was diagnosed in 51 (48%) patients, with 75% of pain states definite and 25% probable neuropathic pain. The most common etiology was degenerative disease of the spinal column causing radiculopathy. At the study visit, 11 patients (22% of neuropathic pain patients) were receiving medication that was demonstrated to be effective against neuropathic pain. The geriatrician recommended a trial of a new medicine for 17 patients, but only six continued the medication going forward. Neuropathic pain was surprisingly common in our cohort. Finding effective pain medication is challenging due to comorbidities, possible side effects, and vulnerability in older age. Other pain management methods should be considered.


Benchmarking global fisheries discards.
Discarding by fisheries is one of the most wasteful human marine activities, yet we have few estimates of its scale. Reliable estimates of global discards are essential for sustainable fisheries management. Using United Nations Food and Agriculture Organization databases on country-specific landings, we estimated the discard rate and magnitude for global marine and estuarine capture fisheries using fishery-specific discard rates derived from direct observations and global gear-specific discard rates estimated within a Bayesian modelling framework. An estimated 9.1 million tonnes are discarded annually (95% uncertainty interval: 7-16 M t)-or 10.8% of the global catch (95% UI: 10-12%). Encouragingly, this is about half of the annual global discard rate estimated in the late 1980s. Trawl fisheries, especially demersal otter trawls, warrant intensified efforts to reduce discards. Periodic benchmarks of global discards are needed to assess the performance of reduction efforts.


Metal ligation regulates conformational equilibria and binding properties of cavitands.
A self-folding cavitand binds quinuclidinium cation in its vase conformation and lanthanum ions in its kite conformation. Metal coordination provides a novel switching mechanism for the uptake and release of guests.


Effect of anterior capsulotomy on decentration of a two-zone multifocal intraocular lens.
A study was undertaken to determine if can-opener (CO) or continuous curvilinear capsulorhexis (CCC) anterior lens capsulotomy influences decentration of a two-zone multifocal intraocular lens (IOL). Fifty IOLs (25 with polypropylene haptics and 25 with poly[methyl methacrylate] haptics) were implanted following CO, 42 with poly(methyl methacrylate) haptics, following CCC. The extent and direction of decentration was estimated using a photogeometric technique. The haptic material may influence decentration. Continuous curvilinear capsulorhexis was associated with less decentration than CO (0.36 mm and 0.43 mm, respectively). The difference, however, was not statistically significant.


Outdoor adventure for young people with a mental illness.
The study aims to evaluate the efficacy of an Outdoor Adventure Group (OAG) for young people with a mental illness. It was hypothesized that participating in OAG would result in an increase in self-esteem, sense of mastery and social connectedness, compared with those who attended other Psychosocial Recovery Group Program groups based at Orygen Youth Health. In addition, those in the OAG would show an improved performance of personal goals. Twenty-one youths (aged 15 to 25) participated in the OAG and 12 participated in other Psychosocial Recovery Group Program groups and served as the comparison group. Pre- and post-evaluation measures included (i) Rosenberg Self Esteem Scale; (ii) Mastery Scale; (iii) Social Connectedness Scale; and (iv) personal goals for attending the OAG, rated 1-10 on current performance. The groups were based at Orygen Youth Health, Melbourne, Australia and run over an 8 to 10-week period. Participants of the OAG experienced an improvement in self-esteem (P = 0.001) and mastery (P = 0.001); these changes were not observed in the controls. There were a total of 80 personal goals for the OAG, with an average of 3.81 per person, and performance significantly improved in 66 (82.5%) goals. There were 10 categories of goals; the most common goals were related to self-improvement and social skills development. Increased self-esteem and mastery, and achievement of personal goals gained through the OAG, may facilitate, or be a precursor to, a young person's psychosocial recovery.


Effects of team coordination during cardiopulmonary resuscitation: a systematic review of the literature.
The purpose of this study is to identify and evaluate to what extent the literature on team coordination during cardiopulmonary resuscitation (CPR) empirically confirms its positive effect on clinically relevant medical outcome. A systematic literature search in PubMed, MEDLINE, PsycINFO and CENTRAL databases was performed for articles published in the last 30 years. A total of 63 articles were included in the review. Planning, leadership, and communication as the three main interlinked coordination mechanisms were found to have effect on several CPR performance markers. A psychological theory-based integrative model was expanded upon to explain linkages between the three coordination mechanisms. Planning is an essential element of leadership behavior and is primarily accomplished by a designated team leader. Communication affects medical performance, serving as the vehicle for the transmission of information and directions between team members. Our findings also suggest teams providing CPR must continuously verbalize their coordination plan in order to effectively structure allocation of subtasks and optimize success.


Engineering the filamentous fungus Penicillium oxalicum for rapid, low-background and efficient protein expression.
Filamentous fungi are widely used in the field of recombinant protein expression due to their well-established protein modification systems and excellent secretion capacities. Although Penicillium oxalicum has been developed as an expression host, its potential for efficient and convenient protein production has not been fully exploited. In this study, we obtained an engineered strain by dominant activation of the G protein PGA3 using a point-mutation method based on the low extracellular background P. oxalicum host Δ13A-OamyR. This genetically modified strain, OamyR-QL, with faster cell growth and a more efficient Pamy15A promoter, will be used to construct a novel expression system. The relevant genes and pathways involved in the response to the G protein dominant activation in the engineered strain were revealed by RNA sequencing. Moreover, the transcription activator AmyR was overexpressed in OamyR-QL, resulting in a dramatically enhanced efficiency of the Pamy15A promoter. The construction of an efficient, low-background system by utilizing the G protein-AmyR regulatory pathway provides not only a theoretical reference for the genetic engineering of other filamentous fungal strains, but also a preferable option for the efficient and high purity expression of recombinant proteins in filamentous fungi.


Causal effect of PM1 on morbidity of cause-specific respiratory diseases based on a negative control exposure.
Extensive studies have linked PM2.5 and PM10 with respiratory diseases (RD). However, few is known about causal association between PM1 and morbidity of RD. We aimed to assess the causal effects of PM1 on cause-specific RD. Hospital admission data were obtained for RD during 2014 and 2019 in Beijing, China. Negative control exposure and extreme gradient boosting with SHapley Additive exPlanation was used to explore the causality and contribution between PM1 and RD. Stratified analysis by gender, age, and season was conducted. A total of 1,183,591 admissions for RD were recorded. Per interquartile range (28 μg/m3) uptick in concentration of PM1 corresponded to a 3.08% [95% confidence interval (CI): 1.66%-4.52%] increment in morbidity of total RD. And that was 4.47% (95% CI: 2.46%-6.52%) and 0.15% (95% CI: 1.44%-1.78%), for COPD and asthma, respectively. Significantly positive causal associations were observed for PM1 with total RD and COPD. Females and the elderly had higher effects on total RD, COPD, and asthma only in the warm months (Z = 3.03, P = 0.002; Z = 4.01, P < 0.001; Z = 3.92, P < 0.001; Z = 2.11, P = 0.035; Z = 2.44, P = 0.015). Contribution of PM1 ranked first, second and second for total RD, COPD, and asthma among air pollutants. PM1 was causally associated with increased morbidity of total RD and COPD, but not causally associated with asthma. Females and the elderly were more vulnerable to PM1-associated effects on RD.


Pharmacokinetics of dietary phenethyl isothiocyanate in rats.
Phenethyl isothiocyanate (PEITC) is a dietary component present in cruciferous vegetables and reported to have chemopreventive properties. Previous reports of PEITC pharmacokinetics have measured total ITC (PEITC and its metabolites) in plasma. Our objective was to examine the dose-dependent pharmacokinetics and oral bioavailability of unchanged PEITC, as well as its pH- and temperature-dependent stability and its serum protein binding. Stability was studied at different pH values at room temperature and 4 degrees C. Protein binding was determined by equilibrium dialysis. For the pharmacokinetics study, male Sprague-Dawley rats were administered with PEITC at doses of 2, 10, 100, or 400 micromol/kg intravenously or 10 or 100 micromol/kg orally. Plasma samples were analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted by WinNonlin and ADAPT II. Phenethyl isothiocyanate was stable in aqueous buffers at pH 7.4 with half-lives of 56.1 and 108 h at room temperature and 4 degrees C, respectively. The free fraction of PEITC in rat serum was 0.019. The clearance (Cl) at a low dose of PEITC (2 micromol/kg) was 0.70 +/- 0.17 L h(-1) kg(-1) with an apparent volume of distribution (Vss) of 1.94 +/- 0.42 L/kg. At higher doses, Cl tended to decrease, whereas Vss increased. Oral bioavailability of PEITC was 115 and 93% at doses of 10 and 100 micromol/kg, respectively. A three-compartment model with Michaelis-Menten elimination and distribution was found to best characterize the plasma concentration profiles. Phenethyl isothiocyanate is stable in biological samples, with increased stability under refrigerated conditions. It has high oral bioavailability, low clearance, and high protein binding in rats; nonlinear elimination and distribution occur following the administration of high doses. This investigation represents the first report of the pharmacokinetics of dietary PEITC.


Cost effectiveness analysis of school based Mantoux screening for TB infection.
To assess the cost-effectiveness of adding school based Mantoux screening programs to the New South Wales current TB prevention strategy. A decision analysis model compared the costs and consequences of screening strategies against the current no-screen strategy. Costs associated with screening and with treating future cases of TB were considered. Consequences considered were deaths and adult cases of TB prevented. The study was based on data from prevalence surveys conducted in 1992 and 1994 in Central and South Western Sydney, New South Wales. Screening strategies considered were screening all or only overseas born (OSB) 6 year olds and all or only OSB 14 year olds in school settings. Screening 14 year olds prevented more deaths and adult cases of TB than screening 6 year olds for a similar cost. For both age groups targeted screening of OSB children was more cost-effective than screening all children. Targeted screening of 14 year olds--the most cost effective option--cost $17,956 (costs and benefits discounted at 5%) per adult case prevented, equivalent to approximately $130,000 per life year saved. The cost-effectiveness ratios decline substantially if lower discount rates and less conservative assumptions are applied. Targeted screening was more cost effective than screening all children, however, there are ethical implications of targeting a group based on their origin of birth. As prevention and control of TB continues to be a high priority for NSW, the implications of a school based screening program should be seriously considered.


Post-stroke fatigue.
Post-stroke fatigue is still a relatively unexplored, often neglected condition. The fatigue often manifests as physical and mental lack of energy, and many patients mention fatigue as one of the most difficult sequels to which they have to adjust. Our aim was to assess the fatigue in 35 three-month post-stroke patients and its relation to personal and stroke-related factors, and to compare them with 35 age- and sex-matched healthy control subjects. The main outcome measures for the fatigue were Fatigue Severity Scale (FSS) and Multidimensional Fatigue Inventory (MFI-20). Barthel index was used for functional status assessment, while anxiety and depressive symptoms were evaluated using Hospital Anxiety and Depression Scale (HADS). Study results showed fatigue to be frequent (45%) and often severe. Post-stroke patients showed higher values of general fatigue dimensions, physical fatigue and reduced activity. The number of subjects reporting fatigue problems on the FSS and MFI-20 scales was significantly greater in the stroke group (16/35; 45%) than in the control group (4/35; 11%; chi2 = 12.5; P < 0.001). Considering associations between fatigue and Barthel index score, age, sex, HADS-A (anxiety) and HADS-D (depression) scores, statistically significant associations were recorded between fatigue and anxiety (P = 0.01) and depression symptoms (P = 0.02). Global fatigue showed positive correlation with Barthel index score too (P = 0.01). Multivariate analysis showed that anxiety and depression symptoms could predict post-stroke fatigue (adjusted R2 = 0.556; P < 0.05). Clinical trials and follow-up studies to find an effective treatment for patients with post-stroke fatigue are warranted.


Brainstem and subcortical regions volume loss in patients with degenerative cervical myelopathy and its association with spinal cord compression severity.
In recent years, structural and functional reorganization of the brain and changes in brainstem structural connectivity have been shown in patients with degenerative cervical myelopathy (DCM). We hypothesized that volume loss in the basal ganglia, thalami, and brainstem structures exists and is associated with spinal cord compression severity in patients with DCM. Forty-seven patients with DCM and 25 patients with cervical radiculopathy were evaluated using cervical spinal cord and brain magnetic resonance imaging (MRI). Brainstem structures, basal ganglia, and thalami volumes were evaluated with FreeSurfer and compared between groups with correction for individual intracranial volume, as well as patient age and sex. Additionally, spinal cord MRI data were analysed with the Spinal Cord Toolbox, and cross-sectional area (CSA) and fractional anisotropy (FA) values were calculated. Correlations between MR-morphometry data and spinal cord structural changes, as well as disease duration, were also evaluated in patients with DCM. A statistically significant reduction in the volume of the whole brainstem was revealed in the DCM group compared to the radiculopathy group (p < 0.01, FDR-corrected). Additionally, reductions in medulla oblongata, pons and midbrain volumes were found in patients with DCM (p < 0.01, p < 0.01 and p < 0.05, respectively, FDR-corrected). Additionally, a trend in the loss of volume of the left putamen was found (p = 0.087, FDR-corrected). Furthermore, medulla oblongata volume was correlated with spinal cord compression severity (R = 0.54, adjusted p < 0.001) and white matter damage (R = 0.46, adjusted p < 0.05) in patients with DCM. Negative correlations between the duration of the disease and the severity of spinal cord compression (R = -0.42, adjusted p < 0.05) and white matter damage (R = -0.49, adjusted p < 0.05) were also revealed, as well as a trend toward a negative association between the duration of the disease and the volume of the medulla oblongata (R = -0.35; adjusted p < 0.1). We revealed a reduction in the volume of brainstem structures in patients with DCM compared to patients with radiculopathy. Moreover, we found that these changes are associated with cord compression severity.


The long-term development of public attitudes towards people with epilepsy in the Czech Republic: 1981, 1984, 1998 and 2009 studies.
The long-term development of public attitudes towards people with epilepsy (PWE) was studied. Four questions (Q) used in Czech questionnaires for studies in 1981, 1984, 1998 and 2009 concerned: Q1, familiarity with the concept of epilepsy; Q2, tolerance towards children with epilepsy; Q3, whether epilepsy is considered to be a mental disease; and Q4, attitudes towards employment of PWE. The quality of information about epilepsy increased significantly between 1981 and 1998, 1981 and 2009, and 1998 and 2009. The 1981 and 1984 studies reflected a level of information inferior to the levels seen in Germany and the USA, and the difference had almost disappeared in 1998 and 2009. The long-term follow-up studies in Czech Republic displayed a permanent increase in knowledge about epilepsy. This may reflect the progress in the spread of information, the efforts of patient associations and specialists and perhaps also a change in general attitudes towards people with disabilities. The dramatic change of information levels in Czech surveys could also reflect the change of the political system in 1989. A question that remains to be answered is the extent to which the positive trend reflects positive attitudes in real life. The answers to questions concerning whether people would be willing to help a person having a seizure remain unsatisfactory. Greater efforts should be made to improve the situation of PWE and to minimize their stigmatization.


Dosimetric and clinical aspects of head and neck cancer reirradiation with intensity modulated radiotherapy techniques over the last decade.
Tumor recurrence in head and neck cancer (HNC) is very common, given that locoregional disease relapse occurs in up to 50% of patients. The clinical approach towards cancer recurrence is either by surgery and/or chemo-radiotherapy. Irrespective of the treatment, the management of HNC recurrence is highly challenging and often administered with palliative intent only. The aim of this work was to analyze clinical and dosimetric aspects, such as dose prescription, organ at risk sparing, overall survival and locoregional control of HNC after reirradiation with intensity modulated radiotherapy techniques based on studies published over the last decade, due to the wide clinical implementation of the intensity modulated radiotherapy and particularly of volumetric modulated arc therapy (VMAT) for this malignancy. A systematic search of the literature was conducted within Pub-med/Medline databases to find relevant studies. Of the 130 articles fulfilling the initial search criteria, 15 were selected for final analysis that encompassed all set requirements. Clinical studies revealed the multitude of factors influencing treatment outcome, including anatomical location, histological tumor type, patient-related factors (smoking / comorbidities), cumulative dose and fractionation schedule, reirradiated volume and time between the irradiation of primary and recurrent tumor. Since the literature reports no specific data related to the type of intensity modulation used in reirradiation or any correlation with treatment outcome, IMRT and VMAT might offer comparable result after HNC reirradiation. Patient selection is potentially the main factor leading to an efficient outcome.


Genomic Selection and Genome-Wide Association Analysis for Stress Response, Disease Resistance and Body Weight in European Seabass.
The majority of the genetic studies in aquaculture breeding programs focus on commercial traits such as body weight, morphology, and resistance against diseases. However, studying stress response in European seabass may contribute to the understanding of the genetic component of stress and its future use to select broodstock whose offspring may potentially be less affected by handling. A total of 865 European seabass offspring were used to measure body weight and stress response. Moreover, a disease challenge experiment with Vibrio anguillarum was conducted in a subset (332) of the above fish to study disease resistance. Fish were genotyped with a 57k SNP array, and a Genome-Wide Association study (GWAS) was performed. Five SNPs were found to be statistically significant, three of which affect stress indicators and body weight (in a subgroup of the population), and a putative SNP affects growth performance, while no SNP associated with resistance to Vibrio was found. A moderate to high genomic heritability regarding stress indicators and body weight was estimated using the Restricted Maximum Likelihood (REML) process. Finally, the accuracy, along with the correlation between Estimated Breeding Values (EBVs) and Genomic Estimated Breeding Values (GEBVs), were calculated for all the traits.


Risk Factors for Local Relapse and Inferior Disease-free Survival After Breast-conserving Management of Breast Cancer: Recursive Partitioning Analysis of 2161 Patients.
The purpose of this study was to analyze risk factors for ipsilateral in-breast relapse and inferior disease-free survival (DFS) after standard adjuvant whole-breast radiotherapy (± boost and systemic treatment) as part of a multimodal breast-conserving approach. Decision trees were built through recursive partitioning analysis (RPA). The median follow-up for all 2161 patients was 114 months (9.5 years). Local relapse in the treated breast was uncommon (actuarial rates after 5 and 10 years were 2.7% and 5.8%, respectively). In RPA, the first split was related to age (52 years), with younger patients having a significantly higher risk of local relapse. The younger patients were stratified further by lymph node ratio (LNR). In patients older than 52 years, lack of endocrine treatment was associated with significantly higher risk. DFS was 80.7% at 10 years. The first split was caused by LNR, and the group with unfavorable LNR (> 0.20) could not be stratified further. Ten-year DFS in this group was as low as 50.6%. Patients with favorable LNR (0-0.20) could be stratified by additional risk factors, in particular primary tumor size. RPA is a suitable method to assign patients with early stage breast cancer to different risk groups, both regarding local relapse and DFS. Although age was a major risk factor for local relapse after breast-conserving management, LNR was associated with both endpoints. The systemic treatment approaches used in this study failed to provide satisfactory DFS in patients with LNR > 0.20 and 2 other subgroups.


Ways to approximate current-distance relations for electrically stimulated fibers.
The behaviour of myelinated and unmyelinated fibers is simulated by a model for extracellular stimulation in order to confirm current-distance phenomena known from experiments. Lower and upper limits for cells stimulated with cathode current are calculated for unmyelinated fibers. In the case of myelinated fibers the threshold depends on the distance from the axon and from the nodes.


Incorporation of whey proteins into cheese curd by using transglutaminase.
A Ca(2+)-independent microbial TGase (transglutaminase) isolated from Streptoverticillium mobaraense was used to obtain whey protein containing novel dairy products. We evaluated the difference both in the curd formation time as well as in the hardness and deformability of the cheese obtained from cow's milk in the presence or absence of the enzyme. The results of our experiments showed that the milk coagulation time was dependent on the step in cheese manufacture at which TGase was added. We analysed the deformability and the hardness of the dairy products obtained either by adding both TGase and the milk-clotting enzyme to the milk sample at the same time or by adding TGase after treating the milk sample for 30 min with the clotting enzyme and cutting the obtained coagulum. TGase treatment conferred a strongly decreased protein content to derived whey. Moreover, when further amounts of whey were added to the milk during the manufacturing process in the presence of TGase, whey-protein-enriched dairy products could also be obtained. Our findings may lead to new biotechnologies for the re-utilization of by-products from dairy plants and contribute to reduction of environmental pollution from whey-protein disposal.


Effects of supramaximal balloon dilatation pressures on adult cricoid and tracheal cartilage: A cadaveric study.
Cricoid fracture is a serious concern for balloon dilatation in airway stenosis. Furthermore, there are no studies examining tracheal rupture in balloon dilatation of stenotic segments. The aim of this study was to evaluate the effect of supramaximal pressures of balloons on the cricoid and tracheal rings. Prospective cadaveric study. Seven cadaveric laryngotracheal complexes of normal adults with intact cricothyroid membranes were acquired. Noncompliant vascular angioplasty balloons (BARD-VIDA) were used for dilatation. The subglottis and trachea were subjected to supramaximal dilatation pressures graduated to nominal burst pressure (NBP) and, if necessary, rated burst pressure (RBP). Larger-diameter balloons, starting from 18 mm size to 24 mm, were used. Dilatations were maintained for 3 minutes. The cricoid ring was disrupted by larger-diameter balloons (22 mm and 24 mm) even at lower pressures (less than NBP) in six cases. Tracheal cartilages were very distensible, and external examination after supramaximal dilatation (24 mm close to RBP) revealed no obvious cartilage fractures or trachealis tears. Histopathological examination revealed sloughing of mucosa in the areas corresponding to balloon placement, but no microfractures or disruption of the perichondrium of tracheal ring cartilages. These results indicate that the cricoid is vulnerable to injury from larger balloons even at lower dilatation pressures. The tracheal cartilages and the membranous wall of the trachea remained resilient to supramaximal dilatation and larger balloons. NA. Laryngoscope, 128:1304-1309, 2018.