Human IPSC 3D brain model as a tool to study chemical-induced dopaminergic neuronal toxicity.
Oxidative stress is caused by an imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS). This imbalance plays an important role in brain aging and age-related neurodegenerative diseases. In the context of Parkinson's disease (PD), the sensitivity of dopaminergic neurons in the substantia nigra pars compacta to oxidative stress is considered a key factor of PD pathogenesis. Here we study the effect of different oxidative stress-inducing compounds (6-OHDA, MPTP or MPP+) on the population of dopaminergic neurons in an iPSC-derived human brain 3D model (aka BrainSpheres). Treatment with 6-OHDA, MPTP or MPP+ at 4 weeks of differentiation disrupted the dopaminergic neuronal phenotype in BrainSpheres at (50, 5000, 1000 μM respectively). 6-OHDA increased ROS production and decreased mitochondrial function most efficiently. It further induced the greatest changes in gene expression and metabolites related to oxidative stress and mitochondrial dysfunction. Co-culturing BrainSpheres with an endothelial barrier using a transwell system allowed the assessment of differential penetration capacities of the tested compounds and the damage they caused in the dopaminergic neurons within the BrainSpheres In conclusion, treatment with compounds known to induce PD-like phenotypes in vivo caused molecular deficits and loss of dopaminergic neurons in the BrainSphere model. This approach therefore recapitulates common animal models of neurodegenerative processes in PD at similarly high doses. The relevance as tool for drug discovery is discussed.


Ischemic and endotoxin pre-conditioning reduce lung reperfusion injury-induced surfactant alterations.
Pulmonary ischemia/reperfusion injury represents a common clinical phenomenon after lung transplantation, pulmonary embolism, and cardiac surgery with extracorporeal circulation. We investigated the influence of ischemic and endotoxin pre-conditioning on gas exchange and surfactant properties in a canine model of ischemia/reperfusion injury. Twenty-six foxhounds underwent 3 hours of warm ischemia of the left lung, followed by 8 hours of reperfusion. Ischemic pre-conditioning was performed for either 5 minutes (IPC-5) or by 2 10-minute ischemic periods (IPC-10), before ischemia. For endotoxin pre-conditioning, dogs were pre-treated by a daily intravenous application of increasing amounts of endotoxin for 6 days. No pre-conditioning was performed in the controls. Bronchoalveolar lavage was performed before ischemia/reperfusion injury (baseline) and after the 8-hour reperfusion period in the non-injured right and in the reperfused left lung. Bronchoalveolar lavage fluids were analyzed for the phospholipid-protein ratio, the content of large surfactant aggregates, the phospholipid and neutral lipid profile, the surfactant protein (SP) content, and for biophysical activity. Severe surfactant alterations were observed in the ischemia/reperfusion-injured left lung, with increased protein concentrations and depressed concentrations of large surface aggregates, SP-B, dipalmitoylated phosphatidylcholine, and phosphatidylglycerol. Endotoxin pre-conditioning and IPC-5 were both capable of greatly preventing the ischemia/reperfusion injury-related deterioration of surfactant properties. IPC-10 exerted no effects. Endotoxin pre-conditioning and IPC-5, but not IPC-10, also prevented loss of gas exchange. Ischemic and endotoxin pre-conditioning may protect against impairment of gas exchange in ischemia/reperfusion injury by restoring physiological surfactant properties.


Administration of fibroblast interferon to patients with advanced breast cancer: possible effects on skin metastasis and on hormone receptors.
Eleven patients with metastasized breast cancer received 8 intramuscular injections of 6 x 10(6) units of human fibroblast interferon over a period of 40 days. The injections did not cause local irritation or inflammation. Fever occurred in only 1 of the 11 patients. Although several types of metastases were monitored, only skin nodules consistently (10 out of 11 patients) exhibited changes that were suggestive of a therapeutic effect of the treatment regimen: either a simple decrease in size of some nodules or central necrosis accompanied by an inflammatory reaction. NK-activity of peripheral blood leukocytes was significantly increased after administration of the first dose; the effect of subsequent injections was less clear. Receptors for estrogens and progestogens were increased in the tumor biopsies of 2 out of 2 and 5 out of 6 patients tested respectively.


[New forms of immunotherapy in uro-oncology : HLA-independent therapeutic approaches with bispecific antibodies and CAR T cells].
Immunotherapies using bispecific antibodies and chimeric antigen receptor (CAR) T cells do not depend on previous activation of T cells by the human leukocyte antigen (HLA) system. These HLA-independent approaches displayed groundbreaking clinical results in hematological malignancies-leading to drug approvals for diseases like acute lymphocytic leukemia (ALL), B-cell Non-Hodgkin's lymphoma and multiple myeloma. Currently, several phase I/II trials are investigating the transferability of these results to solid tumors-especially prostate cancer. Compared to established immune checkpoint blockade, bispecific antibodies and CAR T cells have novel and heterogenous side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Treating these side effects and identifying suitable trial participants requires an interdisciplinary treatment approach.


Educational inequality as a predictor of rising back pain prevalence in Austria-sex differences.
Back pain (BP) represents a widespread public health problem in Europe. The morbidity depends on several indicators, which must be investigated to discover risk groups. The examination of trends in socioeconomic developments should ensure a better understanding of the complex link between socioeconomic-status and BP. Therefore, the role of social inequalities for BP has been investigated among Austrian subpopulations over a 24-year period. Self-reported data from nationally representative health surveys (1983-2007) were analyzed and adjusted for self-report bias (N=121 486). Absolute changes (ACs) and aetiologic fractions (AF) were calculated to measure trends. To quantify the extent of social inequality, the relative index of inequality was computed based on educational levels. The prevalence of BP nearly doubled between 1983 and 2007. When investigating educational groups, subjects with low educational level were most prevalent. Obese persons generally showed higher rates of BP than non-obese subjects. Continuously rising trends across the different educational groups were more evident in men. The AC was highest in obese men with high education (+32.9%). Education-related inequalities for BP were more evident in men than women. Educational level is an important social indicator for BP. A gradient for low to high educational level in the trends of BP prevalence was clearly identified and stable only among men. We presume that the association 'education' and 'physical workload leading to BP' is more relevant for men than for women. The implementation of effective approaches to BP, in combination with target group-specific interventions focusing on educational status, is recommended.


Involvement of glutamate, oxidative stress and inducible nitric oxide synthase in the convulsant activity of ciprofloxacin in mice.
This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD(50)) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO) production and malondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD(50) of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with L-arginine. The elevation induced by the clonic CD(50) of ciprofloxacin in brain glutamate level was not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate and MDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD(50) of ciprofloxacin produced an increase in inducible but not in neuronal NO synthase mRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levels with consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacin-induced convulsive seizures.


Herb-drug interaction: pharmacokinetics and pharmacodynamics of anti-hypertensive drug amlodipine besylate in presence of Lepidium sativum and Curcuma longa.
Effects of Lepidium sativum and Curcuma longa were investigated on pharmacokinetics and pharmacodynamics of antihypertensive drug (amlodipine).Hypertensive rats were treated with amlodipine, Lepidium sativum, Lepidium sativum + amlodipine, Curcuma longa and Curcuma longa + amlodipine, and their blood pressures were measured. Amlodipine in plasma samples was analysed using UPLC-TQD. Product ions of amlodipine were monitored at m/z 409.18 > 238 and 409.18 > 294, and of nitrendipine at m/z 361.16 > 315.1 and 361.16 > 329.10.Lepidium sativum + amlodipine treatment showed highest reduction in systolic blood pressure (SBP). Mean anti-hypertensive effect of Lepidium sativum and Curcuma longa was similar to amlodipine. Mean SBPs (1-24 h) of amlodipine, Lepidium sativum, Lepidium sativum + amlodipine, Curcuma longa and Curcuma longa + amlodipine-treated animals were found as 149.5 ± 2.4 mmHg, 151.6 ± 1.09 mmHg and 141.8 ± 2.5 mmHg, 154.9 ± 2.2 mmHg and 144.4 ± 2.6 mmHg (p-value ≤0.05), respectively. Lepidium sativum and Curcuma longa significantly increased amlodipine Cmax by 83% (p-value 0.018) and 53% (p-value 0.035), and AUC0-t by 48% (p-value >0.05) and 56% (p-value 0.033), respectively.Results of pharmacokinetic and pharmacodynamic studies are in agreement. Lepidium sativum and Curcuma longa augment antihypertensive effect of amlodipine, which is also supported by pharmacokinetic observations.


Trait Aggression is Reflected by a Lower Temporal Stability of EEG Resting Networks.
Trait aggression can lead to catastrophic consequences for individuals and society. However, it remains unclear how aggressive people differ from others regarding basic, task-independent brain characteristics. We used EEG microstate analysis to investigate how the temporal organization of neural resting networks might help explain inter-individual differences in aggression. Microstates represent whole-brain networks, which are stable for short timeframes (40-120 ms) before quickly transitioning into other microstate types. Recent research demonstrates that the general temporal stability of microstates across types predicts higher levels of self-control and inhibitory control, and lower levels of risk-taking preferences. Given that these outcomes are inversely related to aggression, we investigated whether microstate stability at rest would predict lower levels of trait aggression. As males show higher levels of aggression than females, and males and females express aggression differently, we also tested for possible gender-differences. As hypothesized, people with higher levels of trait aggression showed lower microstate stability. This effect was moderated by gender, with men showing stronger associations compared to women. These findings support the notion that temporal dynamics of sub-second resting networks predict complex human traits. Furthermore, they provide initial indications of gender-differences in the functional significance of EEG microstates.


The crystal structure of pneumococcal surface antigen PsaA reveals a metal-binding site and a novel structure for a putative ABC-type binding protein.
. The surface protein PsaA of the pathogenic bacterium Streptococcus pneumoniae plays an essential role in its virulence. PsaA is a putative ATP-binding cassette-type (ABC-type) binding protein involved in the uptake of Mn2+ and possibly Zn2+ and is considered to be both a potential drug target and and a candidate vaccine component. . The structure of PsaA has been determined to 2.0 A resolution using X-ray crystallography and is the first structure obtained for an ABC-type binding protein from a Gram-positive organism. The protein consists of two (beta/alpha)4 domains linked together by a single helix. A metal-binding site is formed in the domain interface by the sidechains of His67, His139, Glu205 and Asp280 and is occupied in the structure. . The structural topology of PsaA is fundamentally different from that of other ABC-type binding proteins determined thus far in that PsaA lacks the characteristic 'hinge peptides' involved in conformational change upon solute uptake and release. In our structure, the metal-binding site is probably occupied by Zn2+. The site seems to be well conserved amongst related receptors from both Gram-positive and Gram-negative bacteria.


[Eversion orchidopexy as prophylaxis for recurrence of testicular torsion].
In patients with torsion of the testis, in addition to the urgency of early recognition and immediate operation, it is questionable which method should be used to prevent renewed torsion of the affected and/or contralateral testis with the least damage and most enduring results. Direct suturing or indirect adhesion fixation are recommended as alternative methods. A review of the literature has shown, however, that recurrence of testicular torsion can occur in many cases and that in some cases this leads to complete anatomical or functional loss of the testis. As a logical continuation of a successful pilot study, it was retrospectively investigated by means of a structured questionnaire whether the known eversion operations according to Jaboulay or Kocher for the treatment of idiopathic hydrocele of the testis were also suitable as organ-sparing and enduring procedures for the prophylaxis of recurrent testicular torsion. In 53 out of 76 patients who were treated exclusively for testicular torsion by means of eversion orchidopexy between 1988 and 2008, no evidence of any subsequent recurrent testicular torsion or any other testicular disease was found by means of a structured questionnaire 1-21 years later. Occasional cicatricial symptoms that were of no clinical significance were found in only 5 cases (9.4%). On the basis of these results it may be concluded that eversion orchidopexy can be considered to be a safe and effective method for the prophylaxis of recurrent testicular torsion in comparison to alternative methods.


Well-differentiated abdominal liposarcoma: experience of a tertiary care center.
We presented abdominal liposarcoma cases diagnosed and managed in a tertiary care center and also conducted a literature review on main features of this tumor. Chart reviews of eight cases were conducted, and clinical, surgical, histopathological, and follow-up data were recorded. Overall, complete surgical resection was performed with adjacent organ resection in 25% of cases, and radiotherapy was not administered. Recurrence was developed in only one case and died after 2 years and 3 months, and other cases are under follow-up without recurrence. Histopatological examinations revealed findings of well-differentiated liposarcoma. According to our surgical experience, the surgical margin positivity may not be a determining factor for the survival of patients with well-differentiated liposarcoma, and in the absence of macroscopic invasion, adjacent organ resection may not be required. Radiotherapy may not be preferred when complete resection of abdominal mass was achieved.


JAAM nationwide survey on the response to the first wave of COVID-19 in Japan. Part II: how did medical institutions overcome the first wave and how should they prepare for the future?
To investigate and clarify the surge capacity of staff/equipment/space, and patient outcome in the first wave of coronavirus disease (COVID-19) in Japan. We analyzed questionnaire data from the end of May 2020 from 180 hospitals (total of 102,578 beds) with acute medical centers. A total of 4,938 hospitalized patients with COVID-19 were confirmed. Of 1,100 severe COVID-19 inpatients, 112 remained hospitalized and 138 died. There were 4,852 patients presumed to be severe COVID-19 patients who were confirmed later to be not infected. Twenty-seven hospitals (15% of 180 hospitals) converted their intensive care unit (ICU) to a unit for COVID-19 patients only, and 107 (59%) had to manage both severe COVID-19 patients and others in the same ICU. Restriction of ICU admission occurred in one of the former 27 hospitals and 21 of the latter 107 hospitals. Shortage of N95 masks was the most serious concern regarding personal protective equipment. As for issues that raised ICU bed occupancy, difficulty undertaking or progressing rehabilitation for severe patients (42%), and the improved patients (28%), long-lasting severely ill patients (36%), and unclear isolation criteria (34%) were mentioned. Many acute medicine physicians assisted regional governmental agencies, functioning as advisors and volunteer coordinators. The mortality rate of COVID-19 in this study was 4.1% of all hospitalized patients and 12.5% (one in eight) severe patients. The hospitals with dedicated COVID-19 ICUs accepted more patients with severe COVID-19 and had lower ICU admission restrictions, which could be helpful as a strategy in the next pandemic.


Effect of low-level laser therapy on seminiferous epithelium: a systematic review of in vivo studies.
Laser therapy has proved effective in the treatment of different tissue injuries but little is known about its effect on the testis. The aim of this review was to synthesize research on the in vivo effect of low-level laser therapy on the seminiferous epithelium. A search was performed in the PubMed/Medline, Scopus, Web of Science, and LILACS databases. The initial search retrieved 354 references, and five articles that met the eligibility criteria were selected. In general, the studies showed that laser therapy exerted a positive effect on the germ cell population; however, there was considerable variation in the laser parameters, as well as in the experimental models and methods of tissue analysis used. In conclusion, further studies determining the biostimulation parameters of laser therapy in the testis are necessary in order to provide a basis for the possible application of this technique to the restoration of the human seminiferous epithelium and consequent treatment of some male reproductive disorders.


Endoscopic prosthesis augmentation of the lower esophageal sphincter in swine.
Endoscopically delivered prostheses are safe, durable, and may augment a defective lower esophageal sphincter (LES). Pigs were studied as normal-LES or LES-weakened animals. A novel endoscopic delivery system was developed in order to place multiple hydrogel prostheses into the LES submucosa. Histopathology sections evaluated ultimate durability and the relationship of the prostheses to esophageal anatomy. Overall, 97% of 179 prosthesis delivery attempts were successful. LES-weakened animals had LES pressures return to normal or supranormal values at 2 weeks and 2 months after prosthesis augmentation. Weakened gastric yield pressures improved to normal values at 2 weeks after prosthesis augmentation. The thickness of the muscular layers and the mucosal integrity of the esophagus was unaffected by the retained prostheses. Endoscopically delivered hydrogel prostheses are safe and durable. These prostheses can successfully augment a defective sphincter without recognizable damage to the esophagus.


The application of a simple, sensitive disc assay for sialyltransferase activity to particulate and soluble enzyme preparations and its use in measuring enzymatic activity in human plasma samples.
A simple assay for the determination of sialyltransferase activity is described. The method involves the isolation of the radioactive reaction product on cellulose paper discs washed with trichloroacetic acid, thereby greatly facilitating the handling of large numbers of assays. This procedure is both more accurate and more sensitive than that involving precipitation with protein denaturants and separation by centrifugation, and is applicable to both soluble and particulate enzyme preparations. The application of the method to the determination of sialytransferase in human plasma is detailed. Enzyme activity is elevated two-fold in both cancer patients and patients with non-malignant disease. This suggests that the diagnostic use of determinations of sialyltransferase activity may be limited by its non-specificity.


An initial strategy for comparing proteins at the domain architecture level.
Ideally, only proteins that exhibit highly similar domain architectures should be compared with one another as homologues or be classified into a single family. By combining three different indices, the Jaccard index, the Goodman-Kruskal gamma function and the domain duplicate index, into a single similarity measure, we propose a method for comparing proteins based on their domain architectures. Evaluation of the method using the eukaryotic orthologous groups of proteins (KOGs) database indicated that it allows the automatic and efficient comparison of multiple-domain proteins, which are usually refractory to classic approaches based on sequence similarity measures. As a case study, the PDZ and LRR_1 domains are used to demonstrate how proteins containing promiscuous domains can be clearly compared using our method. For the convenience of users, a web server was set up where three different query interfaces were implemented to compare different domain architectures or proteins with domain(s), and to identify the relationships among domain architectures within a given KOG from the Clusters of Orthologous Groups of Proteins database. The approach we propose is suitable for estimating the similarity of domain architectures of proteins, especially those of multidomain proteins. http://cmb.bnu.edu.cn/pdart/.


Teaching hand placement for chest compression--a simpler technique.
Simplification of the techniques and teaching of resuscitation are advocated as ways of improving skill acquisition and retention. A simple method for teaching hand placement for chest compression has been described but not validated. The objective of this study was to determine if instructing trainees simply to place their hands in the centre of the chest results in better initial and retained accuracy of hand placement than the usual method of first identifying anatomical landmarks. Volunteers received instruction in basic CPR, being taught hand placement either by the standard method (33 subjects) or the simplified method (32 subjects). They were tested for accuracy of hand position before training, immediately afterwards and 6 weeks later. After training both groups showed an improvement in accuracy of hand placement but there was no significant difference in the degree of improvement between the groups (P=0.345), nor in the level of accuracy achieved (P=0.178). Six weeks after training, the Standard Group demonstrated a statistically significant deterioration in accuracy (P=0.001), whereas the Simple Group did not (P=0.561). By this time, however, there was no longer any difference in accuracy of hand placement for either group compared with before training (Standard Group P=0.912; Simple Group P=0.140). On the positive side, the Simple Group took significantly less time (2.90 s) than the Standard Group (4.43 s) to change from ventilation to chest compression (P=0.000003). Simplifying the teaching of correct hand placement for chest compression does not appear to lead to improvement in acquisition or retention of the skill. However, it does result in a significant reduction in the length of the pauses between ventilation and chest compression.


Dendritic cell deficiencies in pediatric acute lymphoblastic leukemia patients.
Acute lymphoblastic leukemia (ALL) cells are particularly poor at generating anti-leukemia immunity, despite residing in lymphoid organs. To assess a potential role of dendritic cells (DC) in poor anti-leukemia immunity, we analyzed peripheral blood DC in 55 pediatric ALL patients at the time of initial diagnosis and 19 age-matched healthy controls. Dendritic cells were identified by their expression of HLA-DR, lack of B, T, NK, and monocyte markers, and expression of CD11c (myeloid DC(mDC)) or BDCA-2 (plasmacytoid DC(pDC)) using flow cytometry. We found that in children with B-lineage ALL, numbers of both mDC and pDC were significantly reduced (P = 0.0001). In contrast, T-lineage ALL patients showed normal pDC and significantly elevated mDC (P = 0.003) levels, with normal expression of HLA-DR and co-stimulatory molecules. A decrease in DC could not be explained by general impairment of myelopoiesis, as we could not demonstrate a correlation of DC numbers with granulocyte/monocyte numbers in patients with B-lineage ALL. However, aberrant expression of myeloid surface markers on leukemic blasts was frequent in patients lacking myeloid DC indicating a potential block of DC differentiation. Thus, depletion of DC in B-lineage ALL patients may contribute to poor anti-leukemia immune responses.


The influence of clips on scars after EMR: clip artifact.
Laterally spreading lesions ≥20 mm are conventionally removed by EMR. Endoscopic clips are increasingly used to mitigate the risk of delayed bleeding. Clips may alter the endoscopic appearance of the scar after EMR, interfering with the assessment of adenoma recurrence. We aimed to evaluate this. Prospective, single-center data from the Australian Colonic Endoscopic resection study (January 2011-May 2015) were analyzed. Patients undergoing EMR of laterally spreading lesions with endoscopic clips used at the EMR defect were eligible. Data included patient and lesion characteristics and procedural, clinical, and histologic outcomes. Clips were used in 111 of 885 lesions (12.5%). A total of 62 of 111 clipped lesions had standardized, high-definition, white light, and narrow-band images of the scars after EMR at first surveillance colonoscopy, and the patients were enrolled. Analysis of the images showed 4 situations: a bland scar (N = 27), residual adenoma (N = 6), mucosal elevation with normal pit pattern (N = 14), or granulation tissue related to the presence of residual clips (N = 15). The latter 2 entities were termed post-EMR scar clip artifact (ESCA). Overall, 29 of 62 previously clipped EMR sites (46.8%) had ESCA at a median follow-up of 5.2 months. Twenty scars had residual clips, and 15 of 20 (75.0%) showed ESCA (P = .002). Lesions clipped for prophylaxis of bleeding were more likely to show ESCA than those clipped for deep mural injury or intraprocedural bleeding (65.5% vs 41.7%; P = .006). ESCA was associated with female sex (P = .010) and greater age (P = .011). ESCA is characterized by a nodular elevation of the mucosa with a normal pit pattern and can occur with or without residual clips. Prophylactic clip closure and the presence of residual clips are associated with ESCA. ( NCT01368289.).


A small IncQ-type plasmid carrying the quinolone resistance (qnrS2) gene from Aeromonas hydrophila.
To investigate the qnrS2 gene encoded by a plasmid obtained from Aeromonas hydrophila. To investigate the full-length sequence of the plasmid carrying qnrS2 (plasmid designated pAHH04) from the strain SNUFPC-A10, the full-length coding sequence of the qnrS region was first amplified. The remaining part of the plasmid was read outwards from this region. The plasmid pAHH04 contained the repC, repA, mobA and mobC genes, and its total size was 7191 bp with a G+C content of 60%. This study describes the full-length sequence of a plasmid carrying the qnrS2 gene from Aer. hydrophila. The plasmid pAHH04 carried plasmid replication and mobilization genes from IncQ-type plasmids. The isolated qnrS2 gene encoded by a plasmid from an Aer. hydrophila strain is of significant importance because it emphasizes the problem of antibiotic resistance as well as the ability of the determinants to spread among the different bacterial species that impact human health.


Effect of occlusal adjustment on globus symptom.
Twenty-two patients seeking treatment for the globus symptom were examined for the presence of symptoms and signs of TMJ dysfunction. They were randomly divided into a treatment group (N = 13) and a placebo group (N = 9) and underwent either simple occlusal adjustment or mock adjustment, respectively. The result of occlusal adjustment was assessed immediately after completion of treatment. The effect of treatment on the globus symptom was assessed 2 to 3 months later in a double-blind study design. Binomial tests showed that there was a significant association between the success of occlusal adjustment and disappearance of the globus symptom. Three patients in the placebo group subsequently received occlusal adjustment and splint therapy. When all patients were interviewed 20 to 44 months later, only two of them reported no improvement. Both had unstable occlusion when the treatment was terminated.


Design of protein homocystamides with enhanced tumor uptake properties for (19)F magnetic resonance imaging.
Straightforward and reliable tools for in vivo imaging of tumors can benefit the studies of cancer development, as well as contribute to successful diagnosis and treatment of cancer. (19)F NMR offers an exceptional quantitative way of in vivo imaging of the infused agents because of the lack of (19)F signals from the endogenous molecules in the body. The purpose of this study is to develop molecular probes with appropriate NMR characteristics and the biocompatibility for in vivo applications using (19)F MRI. We have studied the reaction between perfluorotoluene and homocysteine thiolactone resulting in the formation of N-substituted homocysteine thiolactone derivative. It has been shown that the reaction occurs selectively at the para position. This fluorine-labeled homocysteine thiolactone has been employed for the introduction of a perfluorotoluene group as a (19)F-containing tag into human serum albumin. The modified protein has been studied in terms of its ability to aggregate and promote the formation of free radicals. By comparing the properties of N-perfluorotoluene-homocystamide of albumin with N-homocysteinylated albumin, it has been revealed that blocking of the alpha-amino group of the homocysteine residue in the fluorinated albumin conjugate inhibits the dangerous aggregation process, as well as free radical formation. A dual-labeled albumin-based molecular probe for (19)F MRI and fluorescence microscopy has been obtained by functionalizing the protein with both maleimide of a fluorescent dye and a fluorinated thiolactone derivative. The incubation of cells with this conjugate did not reveal any significant reduction in cell viability with respect to the parent albumin. The perfluorotoluene-labeled albumin has been demonstrated to act as a promising agent for in vivo (19)F MRI.


[Percutaneous injection of methyl-metacrylate in osteoporosis and severe vertebral osteolysis (Galibert's technic)].
The authors present their preliminary experiences using methyl-metacrylate by percutaneous injection for the treatment of osteoporosis and osteolysis of the vertebral body and for vertebral angiomas. The injection of cement strengthens the vertebral body and prevents its collapse. The mixture used consist of 4.80 g of powder with 5 cm3 of monomer liquid. The technique is performed with radiological control under neuroleptanalgesia and a local anesthesia before insertion of the needle. This technique gives good results for the treatment of vertebral pain caused by osteoporosis or osteolysis.


Breathing activity in fetal sheep during mechanical ventilation of the lungs in utero.
Effects of mechanical ventilation of the lungs of fetal lambs in utero are described. Feasibility studies were performed acutely on four fetuses at 140-142 days gestational age. Five fetuses were prepared for chronic experiments at 122-128 days gestation. Mechanical ventilation was used to produce changes in fetal blood gases for periods of up to 24 h in acute preparations or for repeated periods of 3-9 h on consecutive days in chronic preparations. This technique permits the study of fetal lambs in utero under conditions which normally occur after birth without producing maternal changes or using anesthesia and whilst the umbilical circulation remains open. Four situations were examined using ventilation in these chronic preparations: (1) expansion of the lungs whilst maintaining fetal normoxia and normocapnia; (2) fetal normoxia and hypocapnia; (3) hyperoxia and normocapnia; (4) hyperoxia and hypocapnia. None of these situations produced continuous fetal breathing, either during ventilation or after switching off the ventilator. We conclude that they do not provide appropriate stimuli to mimic those which normally produce continuous breathing after birth.


Differential mortality rates by ethnicity in 3 influenza pandemics over a century, New Zealand.
Evidence suggests that indigenous populations have suffered disproportionately from past influenza pandemics. To examine any such patterns for Māori in New Zealand, we searched the literature and performed new analyses by using additional datasets. The Māori death rate in the 1918 pandemic (4,230/100,000 population) was 7.3× the European rate. In the 1957 pandemic, the Māori death rate (40/100,000) was 6.2× the European rate. In the 2009 pandemic, the Māori rate was higher than the European rate (rate ratio 2.6, 95% confidence interval 1.3-5.3). These findings suggest some decline in pandemic-related ethnic inequalities in death rates over the past century. Nevertheless, the persistent excess in adverse outcomes for Māori, and for Pacific persons residing in New Zealand, highlights the need for improved public health responses.


Computer tomography of traumatic intracerebral hemorrhagic lesions: the change in density and mass effect with time.
A review of sequential CT examinations on 87 acute nonpenetrating head injury patients with traumatic hemorrhagic lesions has revealed a difference in location and in time course for change in density and mass effect between intracerebral hematoma, hemorrhagic contusion, and diffuse white matter shearing injury.


[Current trends in the treatment of mandibular osteoradionecrosis. Use of a sternocleidomastoid osteomyocutaneous flap].
An osteomusculocutaneous flap using the clavicle, and pedunculated on the sternocleidomastoid muscle, was used in two patients to repair loss of post-radicular mucosa and bone substance. Healing of mucosa and bone consolidation was obtained with evidence of production of bone callus on radiography. The hypothesis advanced to explain this reconstruction of necrosed mandible is the presence of the new vascular supply.


Longitudinal associations between metabolites and long-term exposure to ambient air pollution: Results from the KORA cohort study.
Long-term exposure to air pollution has been associated with cardiopulmonary diseases, while the underlying mechanisms remain unclear. To investigate changes in serum metabolites associated with long-term exposure to air pollution and explore the susceptibility characteristics. We used data from the German population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999-2001) and two follow-up examinations (F4: 2006-08 and FF4: 2013-14). Mass-spectrometry-based targeted metabolomics was used to quantify metabolites among serum samples. Only participants with repeated metabolites measurements were included in the current analysis. Land-use regression (LUR) models were used to estimate annual average concentrations of ultrafine particles, particulate matter (PM) with an aerodynamic diameter less than 10 μm (PM10), coarse particles (PMcoarse), fine particles, PM2.5 absorbance (a proxy of elemental carbon related to traffic exhaust, PM2.5abs), nitrogen oxides (NO2, NOx), and ozone at individuals' residences. We applied confounder-adjusted mixed-effects regression models to examine the associations between long-term exposure to air pollution and metabolites. Among 9,620 observations from 4,261 KORA participants, we included 5,772 (60.0%) observations from 2,583 (60.6%) participants in this analysis. Out of 108 metabolites that passed stringent quality control across three study points in time, we identified nine significant negative associations between phosphatidylcholines (PCs) and ambient pollutants at a Benjamini-Hochberg false discovery rate (FDR) corrected p-value < 0.05. The strongest association was seen for an increase of 0.27 μg/m3 (interquartile range) in PM2.5abs and decreased phosphatidylcholine acyl-alkyl C36:3 (PC ae C36:3) concentrations [percent change in the geometric mean: -2.5% (95% confidence interval: -3.6%, -1.5%)]. Our study suggested that long-term exposure to air pollution is associated with metabolic alterations, particularly in PCs with unsaturated long-chain fatty acids. These findings might provide new insights into potential mechanisms for air pollution-related adverse outcomes.


Isolation and characterization of mouse mesenchymal stem cells.
Mesenchymal stem cells (MSCs) have been studied in regenerative medicine because of their unique immunologic characteristics. However, before clinical application in humans, animal models are needed to confirm their safety and efficacy. To date, appropriate methods and sources to obtain mouse MSCs have not been identified. Therefore, we investigated MSCs isolated from 3 strains of mice and 3 sources for the development of MSCs in a mouse model. Male BALB/c, C3H and C57BL/6 mice were used to isolate MSCs from various tissues including bone marrow (BM), compact bone, and adipose tissue. The MSCs were maintained in StemXVivo medium. Immunophenotypes of the MSCs were analyzed by FACS and their growth potential estimated by the number of colony-forming unit fibroblasts. All MSCs that were isolated from BM, compact bone, and adipose tissue showed plastic-adherent, fibroblastic-like morphologic characteristics regardless of the mouse strain or cell source. However, culture of BM MSCs was less successful than the other tissue types. The FACS phenotype analysis revealed that the MSCs were positive for CD29, CD44, CD105, and Sca-1, but negative for CD34, TER-119, CD45, and CD11b. According to the results of the characterization, the adipose tissue MSCs showed higher growth potential than did other MSCs. The results of this study showed that culture of adipose tissue and compact bone-MSCs was easier than BM MSCs. Based on the results of immunophenotype and growth potential, C57BL/6 AT-MSCs might be a suitable source to establish a mouse model of MSCs.


Malignant Bowel Obstruction: Reappraising the Value of Surgery.
Urgent palliative surgery in the setting of advanced malignancy is associated with significant morbidity, mortality, and cost. Malignant bowel obstruction is the most frequent indication for such intervention. Traditional surgical dogma is often invoked to justify associated risks and cost, but little evidence exists to support surgical over nonsurgical approaches. Evolving evidence may provide more meaningful guidance for treatment selection.


Gastric goblet cell carcinoma concurrent with a neuroendocrine tumor.
Goblet cell carcinoma, a tumor that is assumed to originate from crypt base stem cells, is a distinct type of tumor, that occurs typically in the appendix, however, extra-appendiceal locations were also described in few cases. We herein present a unique case of a 48-year-old male with a diagnosis of primary gastric Goblet cell carcinoma that was initially discovered at the time of an endoscopy performed to evaluate an unremitting abdominal pain that was accompanied by remarkable weight loss; four polypoid fragments of the gastric mucosa were sent for histopathologic examination which showed a moderately differentiated goblet cell carcinoma in addition to classical neuroendocrine tumor. Later, laparoscopic D2 total gastrectomy with appendectomy were performed and confirmed the previously mentioned findings along with a normal histopathology of the appendix.


Evolutionary genomics of miniature inverted-repeat transposable elements (MITEs) in Brassica.
Miniature inverted-repeat transposable elements (MITEs) are truncated derivatives of autonomous DNA transposons, and are dispersed abundantly in most eukaryotic genomes. We aimed to characterize various MITEs families in Brassica in terms of their presence, sequence characteristics and evolutionary activity. Dot plot analyses involving comparison of homoeologous bacterial artificial chromosome (BAC) sequences allowed identification of 15 novel families of mobile MITEs. Of which, 5 were Stowaway-like with TA Target Site Duplications (TSDs), 4 Tourist-like with TAA/TTA TSDs, 5 Mutator-like with 9-10 bp TSDs and 1 novel MITE (BoXMITE1) flanked by 3 bp TSDs. Our data suggested that there are about 30,000 MITE-related sequences in Brassica rapa and B. oleracea genomes. In situ hybridization showed one abundant family was dispersed in the A-genome, while another was located near 45S rDNA sites. PCR analysis using primers flanking sequences of MITE elements detected MITE insertion polymorphisms between and within the three Brassica (AA, BB, CC) genomes, with many insertions being specific to single genomes and others showing evidence of more recent evolutionary insertions. Our BAC sequence comparison strategy enables identification of evolutionarily active MITEs with no prior knowledge of MITE sequences. The details of MITE families reported in Brassica enable their identification, characterization and annotation. Insertion polymorphisms of MITEs and their transposition activity indicated important mechanism of genome evolution and diversification. MITE families derived from known Mariner, Harbinger and Mutator DNA transposons were discovered, as well as some novel structures. The identification of Brassica MITEs will have broad applications in Brassica genomics, breeding, hybridization and phylogeny through their use as DNA markers.


Non-interaction of ketotifen and theophylline in children with asthma--an acute study.
Six asthmatic children participated in an acute crossover randomized study. They received a single dose of aminophylline syrup 6 mg/kg after having received ketotifen syrup 1 mg b.i.d. or placebo for 8 days. Ketotifen did not significantly affect the heart rate, pulse pressure or such pharmacokinetic parameters of theophylline as peak serum level, time to peak, half life and AUC. Thus, ketotifen had no significant effect on the disposition of theophylline.


Cloning and characterization of fructosamine-6-kinase from Arthrobacter aurescens.
Fructosamine-6-kinases (FN6Ks) that catalyze phosphorylation of glycated amino acids, i.e., fructosyl amino acids (FAs), have been shown as a potential recognition element for glycated protein detection. However, there are only two available FN6Ks: those from Escherichia coli which is specific for ε-fructosyl lysine (ε-FK) and Bacillus subtilis which recognizes both ε-FK and α-FA as substrates. In this study, we characterized an FN6K homologue isolated from Arthrobacter, some of whose species are reported to assimilate FA. The BLAST searches of Arthrobacter genomic database, using the bacterial FN6K primary structure information, revealed the presence of an FN6K homologue in Arthrobacter aurescens TC1 strain. Indeed, enzymatic assays confirmed that the putative FN6K from A. aurescens is an FN6K that is specific for ε-FK, although the primary sequence alignments showed similarity of A. aurescens FN6Ks with FN6Ks from B. subtilis and E. coli at the same level. In this study, we describe for the first time the presence of FN6K in Arthrobacter spp. and ε-FK-specific degradation pathway from Gram-positive bacteria, providing important information for the development of FA-recognizing molecules as well as for the FA assimilation system in bacteria.


Intrinsic dopamine and acetylcholine dynamics in the striatum of mice.
External rewards such as food and money are potent modifiers of behaviour1,2. Pioneering studies established that these salient sensory stimuli briefly interrupt the tonic discharge of neurons that produce the neuromodulators dopamine (DA) and acetylcholine (ACh): midbrain DA neurons (DANs) fire a burst of action potentials that broadly elevates DA in the striatum3,4 at the same time that striatal cholinergic interneurons (CINs) produce a characteristic pause in firing5,6. These phasic responses are thought to create unique, temporally limited conditions that motivate action and promote learning7-11. However, the dynamics of DA and ACh outside explicitly rewarded situations remain poorly understood. Here we show that extracellular DA and ACh levels fluctuate spontaneously and periodically at a frequency of approximately 2 Hz in the dorsal striatum of mice and maintain the same temporal relationship relative to one another as that evoked by reward. We show that this neuromodulatory coordination does not arise from direct interactions between DA and ACh within the striatum. Instead, we provide evidence that periodic fluctuations in striatal DA are inherited from midbrain DANs, while striatal ACh transients are driven by glutamatergic inputs, which act to locally synchronize the spiking of CINs. Together, our findings show that striatal neuromodulatory dynamics are autonomously organized by distributed extra-striatal afferents. The dominance of intrinsic rhythms in DA and ACh offers new insights for explaining how reward-associated neural dynamics emerge and how the brain motivates action and promotes learning from within.


SNPs detection by a single-strand specific nuclease on a PNA zip-code microarray.
In this report, a reliable peptide nucleic acid (PNA) microarray-based method for accurately detecting single nucleotide polymorphism (SNP) in human genes is described. The technique relies on the mismatched cleavage activity of a single-strand specific (SSS) nuclease. PCR amplification was performed to prepare gene fragments containing the mutation sites. The amplified fragments were then employed as templates for the SSS nuclease reaction using chimeric probes, modified with biotin at the 5' end and extended with a unique anchoring zip-code complement sequence at the 3' end. The SSS nuclease promotes cleavage of heteroduplex DNAs at base mismatched positions to produce crumbled chimeric probes in the presence of imperfectly matching template strands. In contrast, the probes remain intact when they interact with perfectly matched template strands. Only the non-fragmented probes generate fluorescence signals after treatment with streptavidin-Cy3 on the PNA zip-code array. This methodology was used to successfully genotype selected Korean-specific BRCA mutation sites with wild type and mutant samples. The investigation has led to the development of a reliable SSS nuclease-based system for the diagnosis of human genetic mutations or SNPs.


Appearance-Related Partner Preferences and Body Image in a German Sample of Homosexual and Heterosexual Women and Men.
There is evidence that gender as well as sexual orientation can affect body image. In particular, heterosexual women and homosexual men seem to be more vulnerable to a negative body image compared to homosexual women and heterosexual men. One reason for this may be derived from the fact that heterosexual women and homosexual men try to attract male romantic partners: As men place more importance on physical attractiveness than do women, the pressure to fulfill the sociocultural beauty ideal is thus increased. The present online study investigated differences in appearance-related partner preferences and their associations with measures of body image and eating pathology in homosexual and heterosexual women and men. The non-representative sample consisted of 893 participants (n = 201 lesbian women, n = 192 gay men, n = 349 heterosexual women, and n = 151 heterosexual men), who completed silhouette measures assessing their perception and expectations regarding body fat and muscularity of their own body and the body of a potential romantic partner, as well as questionnaires on drive for thinness, drive for muscularity, and eating pathology. Overall, few differences in appearance-related partner preferences emerged between the four groups. However, compared to heterosexual women, homosexual men appeared to prefer higher muscularity in potential romantic partners, which was also associated with increased drive for thinness and muscularity and increased eating pathology. The present findings indicate that, irrespective of sexual orientation, women and men tend to share similar standards regarding their own and a potential partner's physical appearance, potentially suggesting an increased hegemony of heteronormative beauty ideals in women and men in general.


VO2+ ions in zinc lead borate glasses studied by EPR and optical absorption techniques.
Electron paramagnetic resonance (EPR) and optical absorption spectra of vanadyl ions in zinc lead borate (ZnO-PbO-B2O3) glass system have been studied. EPR spectra of all the glass samples exhibit resonance signals characteristic of VO2+ ions. The values of spin-Hamiltonian parameters indicate that the VO2+ ions in zinc lead borate glasses were present in octahedral sites with tetragonal compression and belong to C4V symmetry. The spin-Hamiltonian parameters g and A are found to be independent of V2O5 content and temperature but changing with ZnO content. The decrease in Deltag( parallel)/Deltag( perpendicular) value with increase in ZnO content indicates that the symmetry around VO2+ ions is more octahedral. The decrease in intensity of EPR signal above 10 mol% of V2O5 is attributed to a fall in the ratio of the number of V4+ ions (N4) to the number of V5+ ions (N5). The number of spins (N) participating in resonance was calculated as a function of temperature for VO2+ doped zinc lead borate glass sample and the activation energy was calculated. From the EPR data, the paramagnetic susceptibility was calculated at various temperatures and the Curie constant was evaluated from the 1/chi-T graph. The optical absorption spectra show single absorption band due to VO2+ ions in tetragonally distorted octahedral sites.


Picosecond energy transfer in a transition metal dichalcogenide-graphene heterostructure revealed by transient Raman spectroscopy.
Intense light–matter interactions and unique structural and electrical properties make van der Waals heterostructures composed by graphene (Gr) and monolayer transition metal dichalcogenides (TMD) promising building blocks for tunneling transistors and flexible electronics, as well as optoelectronic devices, including photodetectors, photovoltaics, and quantum light emitting devices (QLEDs), bright and narrow-line emitters using minimal amounts of active absorber material. The performance of such devices is critically ruled by interlayer interactions which are still poorly understood in many respects. Specifically, two classes of coupling mechanisms have been proposed, charge transfer (CT) and energy transfer (ET), but their relative efficiency and the underlying physics are open questions. Here, building on a time-resolved Raman scattering experiment, we determine the electronic temperature profile of Gr in response to TMD photoexcitation, tracking the picosecond dynamics of the G and 2D Raman bands. Compelling evidence for a dominant role of the ET process accomplished within a characteristic time of ∼4 ps is provided. Our results suggest the existence of an intermediate process between the observed picosecond ET and the generation of a net charge underlying the slower electric signals detected in optoelectronic applications.


Preliminary Evidence for the Enhancement of Self-Conducted Exposures for OCD using Cognitive Bias Modification.
Exposure and Response Prevention (ERP) is the most effective treatment for OCD but it is not accessible to most patients. Attempts to increase the accessibility of ERP via self-directed ERP (sERP) programs such as computerized delivery and bibliotherapy have met with noncompliance, presumably because patients find the exposure exercises unacceptable. Previous research suggests that Cognitive Bias Modification (CBM) interventions may help individuals approach feared situations. The goal of the current study was to test the efficacy of a treatment program for OCD that integrates sERP with CBM. Twenty-two individuals meeting diagnostic criteria for OCD enrolled in our 7-week treatment program. Results suggest that sERP with CBM led to significant reduction of OCD symptoms and functional impairment. Indeed, the magnitude of the effect of this novel treatment, that requires only an initial session with a clinician trained in ERP for OCD, was comparable to that of the gold standard clinician-administered ERP. Moreover, preliminary evidence suggests that CBM interventions targeting interpretation bias may be most effective, whereas those targeting attention and working memory bias may not be so.


Simple management of difficult vesicovaginal fistulas by anterior transvesical approach.
A simple method to repair vesicovaginal fistulas through an anterior transvesical approach is described. The process involves minimal dissection and mobilization of the bladder mucosa to preserve the blood supply to the area of the fistula. There were 29 patients referred to 1 urology unit treated in this way during the last 10 years, with a success rate of 86 per cent after the first operative attempt.


Successful rescue of a child with fall-related multi-organ injuries.
Fall-related injury is a major cause of accidental death and is rarely reported in children. Even successful treatment of children with multi-organ injuries caused by fall from the extreme height has been rarely reported. We herein report a 2-year-old girl who fell from the 10th floor, had multi-organ injuries, and was successfully rescued. The girl sustained multi-organ injuries, such as head injury, closed abdominal injury, as well as fractures of the left limbs, and successfully recovered after two surgeries and supportive treatment. This case illustrates that a child who falls from extreme heights can occasionally be rescued. Early neuroprotective strategies help to improve neurological recovery.


Laparoscopic cortical-sparing adrenalectomy for bilateral pheochromocytoma.
A 32-year-old female with asthma was hospitalized for pneumonia in 2/06. She underwent a CT scan of the chest which revealed an incidental finding of bilateral adrenal masses. On further questioning, she admitted to palpitations and flushing. She was normotensive. Biochemical workup was significant for elevated urinary norepinephrine and normetanephrines, and plasma catecholamine level. MIBG scan showed positive uptake in the left adrenal gland consistent with pheochromocytoma. T2 weighted MRI showed bilateral adrenal masses, left greater than right. After adequate alpha blockade with phenoxybenzamine, the patient underwent a laparoscopic left adrenalectomy. Pathology revealed a 3.5 cm pheochromocytoma. The patient then underwent a right cortical-sparing adrenalectomy to avoid complete adrenal insufficiency and Addisonian crisis. The choice of operation was made realizing the potential for increased bleeding, which was further complicated by the patient's Jehovah's Witness beliefs, which prohibit transfusion of any blood products. At surgery, a small, well-circumscribed mass of the inferior right adrenal gland was found, and excised in its entirety. A postoperative ACTH-stimulation test showed appropriate cortisol response. Pathology revealed a 1.5 cm pheochromocytoma, and the patient recovered uneventfully. Cortical-sparing adrenalectomy has been reported with success rates of 65-100% in avoiding exogenous steroid dependence.(1,2) Bilateral pheochromocytoma remains the most common indication. Risks for both recurrence and malignancy require lifelong follow-up in these patients.


REIN and international collaboration
On the occasion of the 20th anniversary of the REIN (French Renal Epidemiology and Information Network), a summary work on the contributions of the national French ESKD register was carried out. On the issue of its international role, the following key messages were retained. Right from its inception, the REIN registry has been integrated into the family of European registries under the direction of the European society ERA and its registry based at the Academic Medical Centre of Amsterdam. In this context, the registry has been a part of numerous international publications and projects financed by the European Commission. The expertise of the Agency of Biomedicine and REIN on the registries has been sought on several occasions in the context of setting up registries of replacement therapies. Several foreign students outside the European Union have also been able to come and work in the REIN national coordination.


Dermal regeneration in full-thickness wounds in Yucatan miniature pigs using a biodegradable copolymer.
The aim of this study was to assess the performance of a biodegradable dermal substrate in deep dermal skin defects. The substrate consisted of a synthetic biodegradable matrix called Polyactive, which is an elastomeric poly (ether)/ poly (ester) block copolymer. This matrix was manufactured either as a porous substrate, with gradually changing pore size (BISKIN-M), or as a bilayer consisting of a porous underlayer with a fully dense surface layer (BISKIN). Cell-free matrices and matrices seeded with autologous or allogeneic porcine fibroblasts were applied to full-thickness skin wounds in Yucatan miniature pigs. Biopsies were taken at different time intervals up to 24-months post-transplantation. Although all BISKIN substrates showed little or no adherence to the wound bed, the adherence of the BISKIN-M substrates to the underlying wound was achieved within minutes after application. Therefore, only BISKIN-M Polyactive substrates were further evaluated. Wound contraction was inhibited by both cell-free and fibroblast-populated substrates. All substrates showed extensive neovascular and fibrous tissue ingrowth within 2-weeks post-transplantation. Furthermore, during this time period, matrix degradation was observed, starting with the fragmentation of the polymers into particles, which were phagocytized by macrophages. These processes occurred actively up to 3 months and ceased thereafter. Cell-free substrates degraded faster, and also, the collagen deposition was lower as compared with cell-seeded substrates. The tissue surrounding the remnants of the Polyactive substrates after 24-months post-transplantation consisted of a mature connective tissue. The newly formed collagen had the same distribution pattern as observed in normal native dermis. We conclude therefore that treatment of full-thickness skin defects with fibroblast-populated BISKIN-M Polyactive substrates leads to satisfactory dermal regeneration.


The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans in localized and generalized forms of aggressive periodontitis.
To investigate the presence of A. actinomycetemcomitans, including the highly virulent JP2 clone, in young adult patients with aggressive periodontitis, and associate the findings with the two forms of the disease. Seventy Moroccan subjects with aggressive periodontitis, aged less than 35 years, were recruited. Among these, 41 had LAgP and 29 had GAgP. Plaque samples were collected from periodontal pockets and examined using a PCR that detects the presence of A. actinomycetemcomitans and which differentiates between JP2 and non-JP2 genotypes of the bacterium. total of 58 (83%) from the 70 AgP patients were positive for A. actinomycetemcomitans, among whom 77% were positives for the JP2 clone. The JP2 clone was detected in 34 (83%) of the LAgP patients compared to 20 (69%) of the GAgP patients (p = 0.17). Fourteen (20%) of the patients harbored non-JP2 genotypes of A. actinomycetemcomitans, although most of these patients (10/14) also harbored the JP2 clone. The presence of the JP2 clone of A. actinomycetemcomitans is strongly associated with both LAgP and GAgP in young adults in Morocco. This implies that treatment of AgP in this population should include microbiological screening and aim at eradication of the bacterium when present.


Prediction of Loss of Muscle Mass in Sarcopenia Using Ultrasonic Diaphragm Excursion.
The diagnosis of sarcopenia is based on the mass and function of appendicular skeletal muscle. It is not clear whether diaphragm excursion is related to muscle mass loss. We try to fill the gap by measuring ultrasonic diaphragm excursion during quiet breathing (Dq) and forced deep breathing (Df) and test whether they could predict the muscle mass loss in sarcopenia. The subjects are recruited from the elderly patients diagnosed with pulmonary nodules in community physical examination. According to the definition, the subjects were divided into group A (who did not meet the diagnostic criteria for muscle mass loss in sarcopenia) and group B (who met the criteria). Participants were assessed for ultrasonic diaphragm excursion, pulmonary function, and cardiopulmonary exercise testing. Logistic regression was used to assess the correlation between right diaphragm excursion and skeletal muscle mass, and receiver-operating characteristic curve (ROC) was applied to determine the best threshold. We recruited 64 elderly participants: 52 in group A (39 males) and 12 in group B (8 males). The Df in group A were higher than in group B (6.02 (5.44-6.60) vs. 4.31 (3.53-5.09) cm, P=0.008). The difference also exists in FVC, FEV1.0, PEF, Pimax, WRmax, and VO2max, but neither in Dq. Logical regression showed that Df was negatively related to muscle mass (B = -0.525, OR = 0.591 (0.378-0.926), P=0.022), even after adjusted age. Based on ROC, a cutoff value of 5.27 cm (AUC = 0.7783, P=0.0028) was selected, and Df ≤ 5.27 cm indicates the increase in odds of existing muscle mass loss. Ultrasonic diaphragm excursion in forced deep breath is helpful for predicting muscle mass loss in sarcopenia. The trial is registered with ChiCTR1800019742.


Pharmaceutical marketing: the example of drug samples.
Branded drug samples are one of the most important promotional tools that pharmaceutical manufactures employ. Pharmaceutical sales representatives ("drug reps") use samples to gain access to physicians and other prescribers. Sample provision is closely intertwined with visits by drug reps; detailing visits convince physicians to try new products, while sampling maintains the flow of prescriptions. Only drugs with the highest profit margins are sampled. Although physicians believe that samples save patients money, patients who receive samples have higher overall out-of-pocket costs. Most studies have found that patients in financial need are least likely to receive samples. Pharmaceutical marketers pitch samples as a low-risk way to deal with diagnostic uncertainty. In fact, there is no evidence that samples aid diagnosis. Sample availability may compromise patient safety by reducing compliance with guidelines and steering patients towards newer drugs, for which adverse effects have not been well-delineated. Although physicians believe that samples improve adherence for low-income patients, branded samples do not improve access or adherence Samples are not a charitable activity, but are instead a highly effective form of drug marketing. Sampling of branded drugs increase drug costs for everyone. Only a cohesive effort by clinicians, legislators and policymakers can end this practice. Evidence supports a ban on sample distribution of branded products.


The clinical characteristics and prognosis in adult Ph negative acute lymphoblastic leukemia with TP53 aberrations.
Very few reports elucidate the prognosis of patients with TP53 aberrations using both measurable residual disease (MRD) and the status of having undergone allogeneic hematopoietic stem cell transplantation (allo-SCT). In this study, aberrations of TP53 were analyzed using next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) in patients with Philadelphia chromosome-negative (Ph-) ALL enrolled in a prospective single-arm clinical trial at our leukemia center. We analyzed the survival of the patients grouped according to the MRD level at the third month and whether or not received allo-SCT. We found that allo-SCT could improve the OS in patients with TP53 aberrations; Patients having negative MRD at the third month still showed worse 3-year OS and 3-year DFS without undergoing allo-SCT, which is different from previous studies, moreover, the prognostic significance of TP53 deletions was as important as TP53 mutations, the importance of screening both TP53 deletions and mutations in adult Ph- ALL at diagnosis should be emphasized.


HOXA11 promotes lymphatic metastasis of gastric cancer via transcriptional activation of TGFβ1.
Most gastric cancer (GC) patients with early stage often have no lymph node (LN) metastases, while LN metastases appear in the advanced stage. However, there are some patients who present with early stage LN metastases and no LN metastases in the advanced stage. To explore the deeper molecular mechanisms involved, we collected clinical samples from early and advanced stage GC with and without LN metastases, as well as metastatic lymph nodes. Herein, we identified a key target, HOXA11, that was upregulated in GC tissues and closely associated with lymphatic metastases. HOXA11 transcriptionally regulates TGFβ1 expression and activates the TGFβ1/Smad2 pathway, which not only promotes EMT development but also induces VEGF-C secretion and lymphangiogenesis. These findings provide a plausible mechanism for HOXA11-modulated tumor in lymphatic metastasis and suggest that HOXA11 may represent a potential therapeutic target for clinical intervention in LN-metastatic gastric cancer.


Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity.
In obese adipose tissue (AT), hypertrophic expansion of adipocytes is not matched by new vessel formation, leading to AT hypoxia. As a result, hypoxia inducible factor-1⍺ (HIF-1⍺) accumulates in adipocytes inducing a transcriptional program that upregulates profibrotic genes and biosynthetic enzymes such as lysyl oxidase (LOX) synthesis. This excess synthesis and crosslinking of extracellular matrix (ECM) components cause AT fibrosis. Although fibrosis is a hallmark of obese AT, the role of fibroblasts, cells known to regulate fibrosis in other fibrosis-prone tissues, is not well studied. Here we have developed an in vitro model of AT to study adipocyte-fibroblast crosstalk in a hypoxic environment. Further, this in vitro model was used to investigate the effect of hypoxia on adipocyte mechanical properties via ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinases (ROCK) signaling pathways. We confirmed that hypoxia creates a diseased phenotype by inhibiting adipocyte maturation and inducing actin stress fiber formation facilitated by myocardin-related transcription factor A (MRTF-A/MKL1) nuclear translocation. This work presents new potential therapeutic targets for obesity by improving adipocyte maturation and limiting mechanical stress in obese AT.


Cleavage of type 2 adenovirus DNA by HaeIII endonuclease. I. Catalog of HaeIII fragments.
Tye 2 adenovirus DNA was divided into 14 fragments by sequential use of BamI, HsuI, SmaI, anc EcoRI endonuclease. Each fragment was purified by gel electrophoresis and subsequently cleaved with HaeIII endonuclease. From the number of fragments produced, we could calculate the number of HaeIII cleavage sites: there are a total of 187 sites. HaeIII sites were not randomly distributed along the adenovirus chromosome. Most sites were clustered in the G + C-rich left half of the chromosome. The sum of the molecular weights of the HaeIII fragments is 22.4 . 10(6), within 2 % of the molecular weight of adenovirus DNA (22.9 . 10(6).


Plasma unconjugated oestriol and unconjugated oestradiol-17 beta in late pregnancy: individual fluctuation of concentrations from day to day and every 10 minutes.
Plasma unconjugated oestriol (E3) and unconjugated oestradiol-17 beta (E2) were determined by radioimmunoassay. In ten normal women in their last month of pregnancy the individual fluctuation of E3 concentrations (mean of the coefficients of variation, CV) from day to day (over 5 days) was 15.6% (range 6.4--26.2%). The individual fluctuation of E2 determined in eight of these women was 16.9 (10.4--25.5) %. In six of the same women who had blood samples collected every 10 min (for 3 h) the individual fluctuation of E3 concentrations was 13.8 (7.0--25.1) %, and of E2 was 16.1 (11.3--26.0) %. The degree of fluctuation of E3 in individuals was in proportion to the mean concentration, unlike E2, suggesting that in clinical practice individual changes in E3 values would be as easy to interpret at low levels as at high levels. The finding that concentrations of plasma unconjugated E3 fluctuate in individuals no more than for E2 or than reported for total E3, and less than reported for 24-h urinary oestrogens, lends practical support to the theoretical preference for the assay of plasma unconjugated E3 to assess fetoplacental function.


Overview of PAF-Degrading Enzymes.
Because the acetyl group of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) is essential for its biological activity, the degradation of PAF is the most important mechanism that regulates the level of PAF. The enzyme that catalyzes the hydrolysis of acetyl group at the sn-2 position of PAF was termed PAF-acetylhydrolase (PAF-AH). Subsequent research revealed that the PAF-AH family includes intracellular forms called PAF-AH I and PAF-AH II as well as an extracellular isoform, plasma PAF-AH. PAF-AH I forms a complex consisting of catalytic subunits α1, α2, and β regulatory subunits. PAF-AH I was identified from the brain, and previous studies focused on the role of PAF-AH I in brain development. However, subsequent studies found that PAF-AH I is involved in diverse functions such as spermatogenesis, amyloid-β generation, cancer pathogenesis, and protein trafficking. Another intracellular enzyme, PAF-AH II, has no homology with PAF-AH I, although this enzyme shares sequence similarity to plasma PAF-AH. Because PAF-AH preferentially hydrolyzes oxidatively modulated or truncated phospholipids, it is considered to play a protective role against oxidative stress. Homologs of this enzyme are widely distributed among evolutionarily diverse organisms. For example, studies of Caenorhabditis elegans PAF-AH II demonstrate its contribution to epidermal morphogenesis. Extracellular plasma PAF-AH associates strongly with plasma lipoproteins. Because PAF-AH is mainly associated with LDL particles, it is considered to play an anti-inflammatory role by removing oxidized phospholipids generated in LDLs exposed to oxidative stress. In this overview, we describe the crucial roles of these three PAF-degrading enzymes in cell function and cell pathology.


Multiplex developmental disorders. The role of communication in the construction of a self.
This article discusses the integration of various aspects of the child's development, particularly the development of language and communication and the way in which these developments interact to enable the child to construct a coherent sense of self. Multiplex developmental disorder is presented as an example of a disorder that affects several of these crucial strands of development. Recent research and controversies regarding the diagnostic descriptions of multiplex and other pervasive developmental disorders are presented. This discussion is used to illustrate the ways in which such disorders affect not only the individual aspects of development, but the child's ability to form a cohesive sense of self. The implications of these difficulties in self-definition for treating children with disorders that affect a variety of aspects of development are also discussed.


ERAP1, ERAP2, and Two Copies of HLA-Aw19 Alleles Increase the Risk for Birdshot Chorioretinopathy in HLA-A29 Carriers.
Birdshot chorioretinopathy (BSCR) is strongly associated with HLA-A29. This study was designed to elucidate the genetic modifiers of BSCR in HLA-A29 carriers. We sequenced the largest BSCR cohort to date, including 286 cases and 108 HLA-A29-positive controls to determine genome-wide common and rare variant associations. We further typed the HLA alleles of cases and 45,386 HLA-A29 controls of European ancestry to identify HLA alleles that associate with BSCR risk. Carrying a second allele that belongs to the HLA-Aw19 broad antigen family (including HLA-A29, -A30, -A31, and -A33) increases the risk for BSCR (odds ratio [OR] = 4.44; P = 2.2e-03). This result was validated by comparing allele frequencies to large HLA-A29-controlled cohorts (n = 45,386; OR > 2.5; P < 1.3e-06). We also confirm that ERAP1 and ERAP2 haplotypes modulate disease risk. A meta-analysis with an independent dataset confirmed that ERAP1 and ERAP2 haplotypes modulate the risk for disease at a genome-wide significant level: ERAP1-rs27432 (OR = 2.46; 95% confidence interval [CI], 1.85-3.26; P = 4.07e-10), an expression quantitative trait locus (eQTL) decreasing ERAP1 expression; and ERAP2-rs10044354 (OR = 1.95; 95% CI, 1.55-2.44; P = 6.2e-09), an eQTL increasing ERAP2 expression. Furthermore, ERAP2-rs2248374 that disrupts ERAP2 expression is protective (OR = 0.56; 95% CI, 0.45-0.70; P = 2.39e-07). BSCR risk is additively increased when combining ERAP1/ERAP2 risk genotypes with two copies of HLA-Aw19 alleles (OR = 13.53; 95% CI, 3.79-54.77; P = 1.17e-05). The genetic factors increasing BSCR risk demonstrate a pattern of increased processing, as well as increased presentation of ERAP2-specific peptides. This suggests a mechanism in which exceeding a peptide presentation threshold activates the immune response in choroids of A29 carriers.


Nitrite soaking pretreatment induced initial denitrifying nitrite accumulation.
Partial denitrification (PD) could be another method for obtaining nitrite. However, PD startup takes a long time limiting its investigation and application. This study proposed nitrite soaking as a pretreatment method for starting PD. Results showed that denitrifying nitrite accumulation (4.20 mg/L) emerged after previously soaking by 10 mg/L nitrite for 9 h. When the duration was 6 h, comparing different soaked nitrite concentrations, the highest denitrifying nitrite accumulation amount (4.92 mg/L) was obtained in the 20 mg/L group. Nevertheless, high pH of 9 and frequent feeding could further advantage denitrifying nitrite accumulation. Pretreatment as a disturbance would impel the microbial community to change from complete denitrification towards PD.


Mechanisms by which transcription can regulate somatic hypermutation.
Mechanisms for somatic hypermutation (SHM) have proven elusive. An actively transcribed substrate was analyzed to elucidate the role of stem-loop structures (SLSs) in SHM. Analysis with a new computer algorithm indicates that the location and mutability of a base are regulated by: (a) the extent to which it is unpaired, (b) the degree to which it is exposed by stabilization of SLSs containing and flanking it, and (c) the level of transcription that drives supercoiling, which creates and stabilizes SLSs containing unpaired bases vulnerable to mutation. New mechanisms are described by which transcription can differentially stabilize SLSs harboring targeted bases and establish specific base exposure patterns. Assuming that transcription levels correlate with the magnitude of superhelicity induced and the lengths of ssDNA forming SLSs, this analysis accounts for the location of all mutable bases during SHM.


Experimental IgA nephropathy in bile duct ligated rats.
Polymeric IgA and polymeric IgA-containing immune complexes are transported from blood to bile through hepatocyte-bound secretory component. In order to investigate interruption of this transport and its effect on the glomerulus, Sprague-Dawley rats underwent bile duct ligation. Renal tissue obtained at the time of sacrifice was stained by immunofluorescent techniques with antibodies to IgG, IgM, and IgA, and secretory component (SC) and C3. A progressive selective increase in the staining intensity of the glomerular mesangium was observed for IgA, C3, and SC in bile duct ligated rats. These changes were paralleled by a rise in serum IgA and C3. These findings are consistent with the view that glomerular deposition of IgA, C3, and SC in bile duct ligated rats may result from impairment of normal handling of polymeric IgA and polymeric IgA-containing immune complexes.


Sorption in soils and bioaccumulation potential of 2,2'-DiBBPA.
2,2'-Dibromobisphenol A (2,2'-DiBBPA) is frequently detected in the environment. However, the mobility of 2,2'-DiBBPA in the soil environment is poorly understood. The present study examined the effects of soil components such as the NaClO-resistant fraction, dithionite-citrate-bicarbonate -demineralized fraction, humin fraction, black carbon, DOC-removed fraction, exogenous dissolved organic carbon and heavy metal cations on the adsorption of 2,2'-DiBBPA on several types of agricultural soils. The adsorption isotherms on soils and soil components were well fitted to the linear isotherm equation. 2,2'-DiBBPA sorption onto soils was dominated by soil organic matter content (SOM) and affected by exogenous dissolved organic carbon. Linear regression relationships between adsorption capacity (Kd) and soil characteristics were evaluated to predict partitioning of 2,2'-DiBBPA. Black carbon played a predominant role in the adsorption of 2,2'-DiBBPA. Heavy metal ions significantly inhibited the adsorptive behavior of 2,2'-DiBBPA under alkaline conditions. Semiempirical linear relationships were observed between biota-sediment accumulation factors (1.18-2.47)/logarithm of bioconcentration factors (BCFs, 2.49-2.52) of 2,2'-DiBBPA in lugworms and Kd. These results allow for the prediction of the bioaccumulation of 2,2'-DiBBPA in other soils. Furthermore, values of log BCF > 1.0 indicate the preferential bioaccumulation of 2,2'-DiBBPA in biota. These data are of significance for understanding the migration of 2,2'-DiBBPA in agricultural soils and bioaccumulation in organisms.


[Transient expression and identification of gene P and NP of NDV LaSota strain in two different cells].
To Construction of P and NP genes eukaryotic expression vectors of Newcastle Disease Virus LaSota strain,study its reverse genetics and functional genome of NDV. P, NP genes were amplified and cloned into pGEM-T easy vector and then subcloned into pcDNA3.1 (+) expression vector respectively, the recombinant plasmids were named pcDNA3.1 (+)-P and pcDNA3.1 (+)-NP, Recombinant plasmids were transfected into 293 and BHK-21 cells respectively and were detected using IE and Western blot analysis. Expression of P, NP genes were detected and confirmed by the IE and WB analysis. The recombinant eukaryotic plasmids pcDNA3. 1(+)-P, pcDNA3.1 (+)-NP were expressed in 293 and BHK-21 cells successfully. This research may be helpful for further study of reverse genetics and functional genome of NDV.


Developments in Nursing Practice to Address Substance Use in the Perinatal Period.
Since 1972, the year of the inaugural issue of Journal of Obstetric, Gynecologic, & Neonatal Nursing, substance use during pregnancy has remained a public health concern in the United States. This concern is currently exacerbated by factors such as the opioid and stimulant use crisis and widening health and social inequities for many women and families. The purposes of this historical commentary are to describe trends in the perception of women with substance use disorder and their infants and related sociolegal implications and to trace the evolution of related nursing practice and research during the past 50 years. We provide recommendations and priorities for practice and research, including further integration of support for the mother-infant dyad, cross-sectoral collaborations, and equity-oriented practices and policies.


Severe hypercalcaemia due to a parathyroid-type hormone-secreting tumour of the liver treated by hepatic transplantation. A rare combination of biochemical problems and discussion of their management.
It is very rare for a patient to have to be submitted for surgery and anaesthesia with severe hypercalcaemia unresponsive to medical treatment. Problems which may be anticipated are hypertension, hypotension, cardiac dysrhythmias and renal failure. Anaesthesia for liver transplantation also requires a full appreciation of the biochemical, haematological and haemodynamic problems involved. In the present report a patient scheduled for hepatic transplantation had a consistently raised serum calcium level (4 mmol/litre) due to the secretion of a parathyroid-type hormone by hepatic tumour cells. The pre-operative management of hypercalcaemia and intra- and postoperative management of liver transplantation in this patient are presented and discussed.


Identification and functional analysis of changes to the ox-LDL-induced microRNA-124-3p/DLX5 axis in vascular smooth muscle cells.
The microRNA (miR)-mRNA axes involved in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs) proliferation/apoptosis imbalance need to be investigated in more detail. To investigate the function and any relevant changes to miR-mRNA axes in the ox-LDL-induced proliferation/apoptosis imbalance in VSMCs. Human VSMCs were cultured and treated with ox-LDL in vitro. The differentially expressed (DE) miRs and mRNAs in VSMCs following 48-h ox-LDL treatment were detected using RNA sequencing. Candidate miRs and mRNAs were further selected, based on comprehensive bioinformatics analysis. Changes in the expression of candidate miRs and mRNAs in ox-LDL-treated VSMCs were confirmed with quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. The inhibitory effect of candidate miRs on mRNAs were demonstrated using a dual luciferase reporter assay. The functional role of candidate miRs and mRNAs on proliferation, cell cycle and apoptosis of VSMCs were estimated using cell couting kit-8 (CCK-8) and flow cytometry assays, respectively. The RNA sequencing data indicated that 577 mRNAs and 81 miRs were significantly upregulated in VSMCs following ox-LDL treatment. Gene function and pathway enrichment analysis suggested that the DE-mRNAs and miRs participate in the regulation of proliferation, cell cycle and apoptosis. Increased expression of DLX5 with decreasing miR-124-3p levels were confirmed in ox-LDL-treated VSMCs. The miR-124-3p could inhibit the DLX5 level by binding the 3' UTR of DLX5 mRNA. Functional analysis showed that the alteration of miR-124-3p/DLX5 expression mediated the effect of ox-LDL on VSMCs proliferation/apoptosis imbalance. The ox-LDL affects the VSMC proliferation/apoptosis balance via the miR-124-3p/DLX5 axis, which results in VSMC hyperproliferation. The miR-124-3p/DLX5 axis might serve as a therapeutic molecular target to reverse the effect of ox-LDL and prevent atherosclerosis (AS) development and progression.


Volatilised pyrene: A phase 1 study demonstrating a new method of visualising fingermarks with comparisons to iodine fuming.
Pyrene is a fluorescent polycyclic aromatic hydrocarbon that can be volatilised under mild conditions. When fumed, pyrene is rapidly absorbed into the sebaceous residues of fingermarks, enabling their fluorescent visualisation upon excitation with ultraviolet radiation. This new means of fluorescent fingermark detection is more sensitive than the non-fluorescent iodine fuming approach for nonporous surfaces. This is demonstrated here in a phase 1 study using split-print comparisons on metal and glass surfaces. Pyrene-treated fingermarks also retain the volatile fluorophore for comparably long time periods relative to iodine fuming (in the order of hours). The phase 1 study comprised four donors, and 80 natural fingermarks that were grouped into two time periods; aged 24h and 1 week. Iodine fuming was chosen as a reference to showcase the effectiveness of pyrene given it is the most closely-related chemical fuming method in routine use. This study demonstrates that pyrene fuming increases the quantity and quality of fingermark visualisations relative to iodine fuming, and is free of many of the latter method's drawbacks. Preliminary results shown here also show the effectiveness of pyrene fuming on highly patterned surfaces, and its compatibility with the use of gelatine lifters. Pyrene fuming is thus easy to effect, low-cost, and shows great promise as a new means of visualising fingermarks on non-porous surfaces.


[Intravenous infusion of adult adipose tissue stem cells for repairing spinal cord ischaemic lesions. An experimental study on animals].
To assess if a peripheral intravenous infusion of adipose tissue stem cells (ATSC), after an ischemic spinal cord injury can promote selective cell migration and cell survival in the damaged neural tissue. ANIMALS AND METHOD: An ischaemic spinal cord injury was provoked by trapping the abdominal aorta for 20 minutes in 11 male New Zealand rabbits (2.5±0.5kg). They were randomised into two groups: one group (n=5) received an intravenous transfusion of 10±2×10(6) ATSC at 24 hours from the injury, and the control group (n=6) were only given the vehicle. The functional status was assessed, using the Tarlov scale at 24h, and 7 and 14 days. The animals were sacrificed at 14 days and a histological and immunohistochemical study was performed. Complete paraplegia was achieved in both groups. There were no significant differences as regards neurological recovery, which was nil in both cases. In the histological and immunohistochemical study, it was tested to see if there was any bromodeoxyuridine-marked ATSC in the area of the lesion, but there was only a small amount. ATSC are able to migrate and survive in the injured spinal cord after aortic ischaemia after they have been administered intravenously. Intravenous infusion is a harmless procedure with no side effect. No neurological recovery was achieved.


Unorthodox diagnostic procedure in a rare case of intrapericardial malignant schwannoma.
To establish preoperatively the cytology of a large right atrial tumour, an echoguided transcutaneous thin needle aspiration using a transhepatic approach was performed. Cytology suggested myxoma, which had been mimicked by regressive changes within the tumour, while the histologic examination of the removed specimen revealed a malignant pericardial Schwannoma. In spite of this discrepancy we think that solid tumours located at the free atrial wall are accessible to ultrasound guided puncture without great risk.


The innate immune response under the control of the LXR pathway.
Macrophages play essential roles in infection and resolution of inflammation. This review summarizes recent findings that suggest a relevant role for the nuclear receptor liver X receptor (LXR) in the evolution of immune responses. By exerting both positive and negative regulation of specific macrophage gene expression networks, LXRs display anti-inflammatory activities and promote macrophage survival in bacterial infection settings. Agonists that activate the LXR pathway may be used to enhance innate immunity to highly virulent pathogens that otherwise induce macrophage apoptosis as a means to subvert host immune defense.


The Impact of a Preauthorization Policy on the After-hours Utilization of Emergency Department Computed Tomography Imaging.
We evaluated the effects of a streamlined emergency department (ED) policy for CT ordering, pre- and postimplementation, on the completed imaging study rates of all after-hours computed tomography (CT) studies. The study hypothesis was that a streamlined CT ordering process would increase the utilization rates of ED CT. A prospective cohort study was used to estimate the effect of enhancing a preauthorization policy for after-hours CT studies requested through the ED, performed between January 1 and June 30, 2013, and the postimplementation period, performed between January 1 and June 30, 2014. Inclusion criteria were all CT chest, CT abdomen/pelvis, musculoskeletal, neurological, and neuroangiographic examinations performed by ED physicians on adult patients. Pre- and postintervention examination imaging study rates were compared. The period following implementation of the preauthorization policy was associated with a statistically significant increase in utilization for most subtypes of CT examinations (CT chest, CT abdomen/pelvis, and musculoskeletal CT studies), with the exception of neurological examinations, which showed a significant decrease. This study demonstrates a trend toward increased utilization of CT resources after implementation of an ED preauthorization policy with most study types showing significantly increased utilization. In the case of neurological examinations, a potential "substitution effect" was observed, whereby the rates of neuroangiographic studies showed a marked increase, offsetting the decrease in general neurological examinations performed. Departments considering implementation of preauthorization policies should weigh carefully the benefits of ED workflow efficiencies against the potential harms of increased CT use.


Exploring the Pathophysiology of Reinke's Edema: The Cellular Impact of Cigarette Smoke and Vibration.
To explore the isolated or combined effects of cigarette smoke extract (CSE) and vibration on human vocal fold fibroblasts (hVFF) in an in vitro setting in order to elucidate their influence in the pathophysiology of Reinke's edema (RE). Immortalized hVFF were exposed to CSE or control medium under static or vibrational conditions. A phonomimetic bioreactor was used to deliver vibrational patterns to hVFF over a period of 5 days. Cytotoxicity was quantified using a lactate dehydrogenase assay. We employed reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Magnetic Luminex(R) assays (R&D Systems, Minneapolis, MN) to assess the influence on extracellular matrix production, fibrogenesis, inflammation, and angiogenesis. We observed significant changes induced by CSE alone (hyaluronic acid, matrix metalloproteinase 1, Interleukin-8, cyclooxygenase [COX]1, COX2, vascular endothelial growth factor [VEGF]D), as well as settings in which only the combination of CSE and vibration led to significant changes (transforming growth factor beta 1, VEGFA, VEGFC). Also, CSE-induced levels of COX2 were only significantly reduced when vibration was applied. We were able to explore the cellular effects of CSE and vibration on hVFF by employing a phonomimetic bioreactor. Whereas cigarette smoke is generally accepted as a risk factor for RE, the role of vibration remained unclear as it is difficult to study in humans. Our data showed that some genes and proteins in the pathophysiological context of RE were only affected when CSE in combination with vibration was applied. NA Laryngoscope, 131:E547-E554, 2021.


Cranial MR imaging findings in Waardenburg syndrome: anophthalmia, and hypothalamic hamartoma.
Cranial MR imaging examination findings of a three and half year old boy with Waardenburg syndrome are described which consisted of bilateral congenital anophthalmia (secondary type), and a hypothalamic hamartoma.


Characteristics of physical prefrailty among Japanese healthy older adults.
The purpose of the present study was to clarify the characteristics of frailty at an early stage (prefrailty) in a healthy elderly Japanese population. The participants were 620 healthy older adults (age range 60-89 years) who were current students or graduates of a community college for older adults in Japan. All participants were evaluated using the Kihon Checklist, a tool developed to screen for frailty in Japan. The participants were categorized by the Fried criteria (lost weight, handgrip strength, walking speed, exhaustion, physical activity) into either a prefrailty (1-2 criteria) or a non-frailty (0 criterion) group. In the logistic regression model for the prevalence of prefrailty, significant and independent determinants were chronic constipation (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.15-3.90, P = 0.016), occurrence of incontinence (OR 2.0, 95% CI 1.39-2.82, P < 0.001), unable to climb stairs (OR 3.0, 95% CI 1.26-7.02, P = 0.013), dry mouth (OR 1.5, 95% CI 1.04-2.22, P = 0.029), a lack of fulfillment (OR 3.2, 95% CI 1.26-7.93, P = 0.015), found easy tasks difficult (OR 2.8, 95% CI 1.30-5.85, P = 0.008) and felt helpless (OR 2.1, 95% CI 1.02-4.39, P = 0.044). These results suggest that the appearance of autonomic failure, oral malfunction and some psychological factors in relation to depressed mood, but not anthropometric measurements, are characteristic of prefrailty. Geriatr Gerontol Int 2017; 17: 1568-1574.


Establishing the clinical utility of autofluorescence spectroscopy for parathyroid detection.
The inability of surgeons to identify parathyroid glands accurately during cervical endocrine surgery hinders patients from achieving postoperative normocalcemia. An intrinsic, near-infrared fluorescence method was developed for real-time parathyroid identification with high accuracy. This study assesses the clinical utility of this approach. Autofluorescence measurements were obtained from 137 patients (264 parathyroid glands) undergoing parathyroidectomy and/or thyroidectomy. Measurements were correlated to disease state, calcium levels, parathyroid hormone, vitamin D levels, age, sex, ethnicity, and body mass index. Statistical analysis identified which factors affect parathyroid detection. High parathyroid fluorescence was detected consistently and showed wide variability across patients. Near-infrared fluorescence was used to identify 256 of 264 (97%) of glands correctly. The technique showed high accuracy over a wide variety of disease states, although patients with secondary hyperparathyroidism demonstrated confounding results. Analysis revealed body mass index (P < .01), disease state (P < .01), vitamin D (P < .05), and calcium levels (P < .05) account greatly for variability in signal intensity. Age, sex, parathyroid hormone, and ethnicity had no effect. This intrinsic fluorescence-based intraoperative technique can detect nearly all parathyroid glands accurately in real time. Its discrimination capacity is largely unlimited by patient variables, but several factors affect signal intensity. These results demonstrate potential clinical utility of optical guidance for parathyroid detection.


Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells.
Engineered T cells have been shown to be highly effective in cancer immunotherapy, although T cell exhaustion presents a challenge for their long-term function. Additional T-cell sources must be exploited to broaden the application of engineered T cells for immune defense and reconstitution. Unlimited sources of pluripotent stem cells (PSCs) have provided a potential opportunity to generate precise-engineered therapeutic induced T (iT) cells. Single-cell transcriptome analysis of PSC-derived induced hematopoietic stem and progenitor cells (iHSPC)/iT identified the developmental pathways and possibilities of generating functional T cell from PSCs. To date, the PSC-to-iT platforms encounter several problems, including low efficiency of conventional T subset specification, limited functional potential, and restrictions on large-scale application, because of the absence of a thymus-like organized microenvironment. The updated PSC-to-iT platforms, such as the three-dimensional (3D) artificial thymic organoid (ATO) co-culture system and Runx1/Hoxa9-enforced iT lymphopoiesis, provide fresh perspectives for coordinating culture conditions and transcription factors, which may greatly improve the efficiency of T-cell generation greatly. In addition, the improved PSC-to-iT platform coordinating gene editing technologies will provide various functional engineered unconventional or conventional T cells. Furthermore, the clinical applications of PSC-derived immune cells are accelerating from bench to bedside.