Calcium mobilization stimulates Dictyostelium discoideum shear-flow-induced cell motility.
Application of hydrodynamic mild shear stress to adherent Dictyostelium discoideum vegetative cells triggers active actin cytoskeleton remodeling resulting in net cell movement along the flow. The average cell speed is strongly stimulated by external calcium (Ca2+, K50%=22 microM), but the directionality of the movement is almost unaffected. This calcium concentration is ten times higher than the one promoting cell adhesion to glass surfaces (K50%=2 microM). Addition of the calcium chelator EGTA or the Ca2+-channel blocker gadolinium (Gd3+) transiently stops cell movement. Monitoring the evolution of cell-surface contact area with time reveals that calcium stimulates cell speed by increasing the amplitude of both protrusion and retraction events at the cell edge, but not the frequency. As a consequence, with saturating external calcium concentrations, cells are sensitive to very low shear forces (20 pN; sigma=0.1 Pa). Moreover, a null-mutant lacking the unique Gbeta subunit does not respond to external Ca2+ changes (K50%>1000 microM), although the directionality of the movement is comparable with that of wild-type cells. Furthermore, cells lacking the inositol 1,4,5-trisphosphate receptor (IP3-receptor) exhibit a markedly reduced Ca2+ sensitivity. Thus, calcium release from internal stores and calcium entry through the plasma membrane modulate cell speed in response to shear stress.


A systematic review of internet-based information on dermatomyositis and polymyositis.
Patients with rheumatic diseases are increasingly using internet-based information to inform healthcare utilization and make treatment decisions. Our aim was to assess the readability and quality of internet-based information on dermatomyositis (DM) and polymyositis (PM). Key words "Dermatomyositis" and "Polymyositis" were searched on 3 commonly used search engines (Google, Yahoo and Bing). The first 3 pages (~30) of search results were examined from each search engine. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index). Quality of information was assessed using the DISCERN tool, Journal of The American Medical Association (JAMA) benchmark criteria and Health on The Net Code (HoN code). We also examined Google Trends® data to determine if there were obvious temporal search patterns. Thirty-two websites were included in the study after duplicates were removed and exclusion criteria were applied. The overall quality was low including DISCERN with a median overall score of 38/80 (interquartile range 12.25), only 4/32 (13%) websites fulfilled all 4 JAMA benchmark criteria, and 9/32 (28%) had HoN code. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index. There was no obvious temporal trend in searches on analysis of Google Trends® data. The overall quality and readability of internet-based information relating to DM and PM is poor. Patients require appropriate information of high quality and readability throughout the course of their disease in order to make informed decisions on their condition including treatment.


Malignant fibrous histiocytoma of the aorta complicated by anuria.
Tumors of the aorta have been reported infrequently in the literature. We report a case of a 63-year-old woman diagnosed with malignant aortic fibrous histiocytoma (also known as fibroxanthosarcoma). She was referred to us with suspected occlusion of the right renal artery in a single functioning kidney, with a clinical picture of anuria during the previous 48 hours. We also review 31 previously published cases in the literature.


Increased expression of claudin-17 promotes a malignant phenotype in hepatocyte via Tyk2/Stat3 signaling and is associated with poor prognosis in patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in Asia; however, the molecular mechanism in its tumorigenesis remains unclear. Abnormal expression of claudins (CLDNs), a family of tight junction (TJ) proteins, plays an important role in the metastatic phenotype of epithelial-derived tumors by affecting tight junction structure, function and related cellular signaling pathways. In a previous study, we used a tissue chip assay to identify CLDN17 as an upregulated gene in HCC. Here we aimed to use molecular biology technology to explore the effect of CLDN17 on the malignant phenotype of HCC and the underlying molecular mechanism, with the objective of identifying a new target for HCC treatment and the control of HCC metastasis. The expression levels of CLDN17 in HCC tissues and histologically non-neoplastic hepatic tissues were explored by immunohistochemistry. Stable transfection of the hepatocyte line HL7702 with CLDN17 was detected by real-time polymerase chain reaction (PCR), western blotting and immunofluorescence. The impact of CLDN17 on the malignant phenotype of HL7702 cells in vitro was assessed by a Cell Counting Kit-8 (CCK8) assay, a Transwell assay and a wound-healing experiment. Western blotting was utilized to detect the activation state of Tyrosine kinase 2 (Tyk2) / signal transducer and activator of transcription3 (Stat3) pathway. A Tyk2 RNA interference (RNAi) was utilized to determine the impact of the Tyk2/Stat3 signaling pathway on the malignant phenotype of hepatocytes. In this work, our research group first found that CLDN17 was highly expressed in HCC tissues and was associated with poor prognosis. In addition, we demonstrated that CLDN17 affected the Stat3 signaling pathway via Tyk2 and ultimately enhanced the migration ability of hepatocytes. In conclusion, we confirmed that the upregulated expression of CLDN17 significantly enhances the migration ability of hepatocytes in vitro and we found that the activation of the Stat3 pathway by Tyk2 may an important mechanism by which CLDN17 promotes aggressiveness in hepatocytes.


Ultrafast launch of slingshot spiders using conical silk webs.
In the Theridiosomatidae spider family, at least three genera (Epeirotypus, Naatlo and Theridiosoma) use their three-dimensional cone-shaped webs as ultrafast slingshots that catapult both the spider and the web towards prey [1-3]. Also known as slingshot spiders, theridiosomatids build three-dimensional conical webs with a tension line directly attached to the center of the web. In 1932, Hingston [1] hypothesized that the slingshot spider releases the tension line using its front legs, while holding the web with its rear legs. Coddington [2] detailed how female spiders meticulously build their webs line-by-line. But lacking to date has been quantification of spider kinematics, such as displacement, velocity and acceleration. Here we report the first quantification of theridiosomatid motion, revealing that slingshot spiders generate the fastest arachnid full body motion through use of their webs for external latch-mediated spring actuation [4].


The DP receptor, allergic inflammation and asthma.
Prostaglandin (PG) D(2) is the major cyclooxygenase metabolite of arachidonic acid produced by mast cells in response to allergen in diseases, such as asthma, atopic dermatitis, allergic rhinitis and allergic conjunctivitis. However, whether PGD(2) regulates allergic process per se, and, if so, whether it facilitates or down-regulates the disease process has remained unknown. PGD(2) exerts its actions by binding to two types of specific cell surface receptor. One is DP (the PGD receptor) and the other is chemoattractant receptor-homologous molecule expressed on Th2. Between the two, the DP receptor has been better characterized since its cDNA cloning in 1994, and novel class of DP antagonists have been and are being developed. Furthermore, mice deficient in DP were generated and have been subjected to several models of allergic diseases to reveal the role of PGD(2) in allergy. In this article, we summarize these findings and provide an overview of the current status of the DP receptor research to discuss the therapeutic potential of modulating the PGD(2)-DP pathway in allergic diseases.


Formation of activated protein C and inactivation of cell-bound thrombin by antithrombin III at the surface of cultured vascular endothelial cells--a comparative study of two anticoagulant mechanisms.
Intact vascular endothelium provides several anticoagulant mechanisms for the maintenance of blood fluidity and the prevention of thrombosis. High-affinity binding of proteolytic active thrombin to thrombomodulin at the cell surface effectively facilitates the activation of the potent anticoagulant protein C (PC). Rapid inactivation of cell-bound thrombin by antithrombin III (ATIII) accelerated by heparin-like structures represents another anticoagulant mechanism. In the present investigation the interference of these two events has been studied. Inhibition of thrombin bound to cultured bovine aortic endothelial cells (BAEC) by ATIII and the effect of the inhibitor on the activation of PC has been studied using purified components of bovine origin. Exposure of thrombin (45 nM) with prewashed confluent BAEC-monolayers for 10 min resulted in the binding of 12% thrombin. The subsequent incubation with various concentrations (0.3-2.4 microM) of ATIII revealed no acceleration of the inhibition of thrombin by ATIII at the endothelial cell surface when compared with the uncatalyzed fluid phase reaction. However, compared with the uncatalyzed fluid phase reaction. However, heparin added to the reaction mixture substantially increased the inactivation of cell-bound thrombin. Modified ATIII that did not possess heparin cofactor activity presented a comparable inactivation pattern for endothelial cell bound-thrombin as native ATIII indicating that heparin-like structures did not accelerate the interaction. When PC (32 nM) and ATIII (1.8 microM) competed for thrombin bound to BAEC, activation of PC was demonstrated within the initial 6 min of the incubation amounting to 62% of the activated PC formation in the absence of ATIII.(ABSTRACT TRUNCATED AT 250 WORDS)


Extracranial internal carotid artery: anatomical variations in asymptomatic patients.
The anatomical variations of internal carotid artery (ICA) are mostly asymptomatic, thus being disregarded and only incidentally diagnosed, with very few symptomatic patients. The awareness of these anomalies is crucial to solve the differential with other neck lesions, preventing accidental injuries during neck surgery. Therefore, the aim of our study is to estimate the prevalence of ICA anomalies, using magnetic resonance angiography (MRA) and computed tomography angiography (CTA). 253 patients underwent head and neck MRA and CTA examinations, with multiplanar and volumetric reformations. For each set of images, the following items were investigated: origin, development, course, persistence of embryonic vessels and anomalous origin of collateral branches. In our series, ICA arose from the bifurcation of the common carotid artery at the level of: C4 in 303 hemi-necks (59.9 %); C3 in 98 hemi-necks (19.3 %); C5 in 57 hemi-necks (11.3 %); C2 in 48 hemi-necks (9.5 %). ICA kinking and/or coiling was found in 105 hemi-necks, and location variation of ICA (reversed-type) in two hemi-necks. In just one case the origin of the ascending pharyngeal artery was from ICA (0.2 %), while an anomalous persistence of the proatlantal artery was noticed in three cases (0.6 %). CTA and MRA showed similar accuracy in detecting ICA anomalies.


Some factors influencing colicin activity between pathogenic and commensal Escherichia coli from the pig.
Commensal strains of Escherichia coli derived from pigs had a broad spectrum of in vitro colicin acitivity against pathogenic serotypes. Of eight pathogenic serotypes tested, only three were colicinogenic and were active against relatively few commensal strains. Colicin activity was influenced by temperature, pH and oxygen tension as well as by the availability of certain nutrients and the presence of trypsin. Lack of colicin activity in intestinal supernatant fluid was ascribed to the concentration of trypsin present. It was concluded that colicins are unlikely to influence the dominance of pathogenic Escherichia coli serotypes in the pig's intestine, except possibly in the colon and rectum where the concentration of trypsin is low.


Neonatal lupus erythematosus progressing into systemic lupus erythematosus. A 15 year follow-up.
An infant with neonatal lupus erythematosus developed systemic lupus erythematosus at the age of 13. The clinical distinction between neonatal lupus erythematosus and familial lupus erythematosus may not be as clear cut as previously reported.


Efficacy and safety of edoxaban compared with warfarin according to the burden of diseases in patients with atrial fibrillation: insights from the ENGAGE AF-TIMI 48 trial.
Non-vitamin K antagonist oral anticoagulants represent a new option for prevention of embolic events in patients with atrial fibrillation (AF). However, little is known about the impact of non-cardiac comorbidities on the efficacy and safety profile of these drugs. In a post hoc analysis of the ENGAGE AF-TIMI 48 trial, we analysed 21 105 patients with AF followed for an average of 2.8 years and randomized to either a higher-dose edoxaban regimen (HDER), a lower-dose edoxaban regimen, or warfarin. We used the updated Charlson Comorbidity Index (CCI) to stratify the patients according to the burden of concomitant disease (CCI = 0, 1, 2, 3, and ≥4). The treatment groups were then compared for safety, efficacy, and net clinical outcomes across CCI categories. There were 32.0%, 7.3%, 42.1%, 12.7%, and 6.0% of patients with CCI scores of 0, 1, 2, 3, and ≥4, respectively. A CCI score ≥4 was associated with significantly higher rates of thromboembolic events, bleeding, and death compared to CCI = 0 (P < 0.05 for each). The annualized rates of the primary net clinical outcome (stroke/systemic embolism, major bleeding, or death) for CCI = 0, 1, 2, 3, or ≥4 were 5.9%, 8.7%, 6.6%, 10.3%, and 13.6% (Ptrend < 0.001). There were no significant interactions between treatment with HDER vs. warfarin and efficacy, safety, and net outcomes across the CCI groups (P-interaction > 0.10 for each). Although increasing CCI scores are associated with worse outcomes, the efficacy, safety, and net clinical outcomes of edoxaban vs. warfarin were independent of the degree of comorbidity present.


[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma].
Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.


Surfactant chain length and concentration influence on the interfacial tension of two immiscible model liquids: a coarse-grained approach.
The interfacial tension between immiscible liquids is studied as a function of a model linear surfactant length and concentration using coarse-grained, dissipative particle dynamics numerical simulations. The adsorption isotherms obtained from the simulations are found to be in agreement with Langmuir's model. The reduction of the interfacial tension with increasing surfactant concentration is found to display some common characteristics for all the values of chain length modeled, with our predictions being in agreement with Szyszkowski's equation. Lastly, the critical micelle concentration is predicted for all surfactant lengths, finding exponentially decaying behavior, in agreement with Kleven's model. It is argued that these findings can be helpful guiding tools in the interpretation of available experiments and in the design of new ones with new surfactants and polymers.


Treatment with Paracetamol is not Associated with Increased Airway Sensitivity and Risk of Asthma in Rats.
Some studies have linked the use of paracetamol (PAR) with adverse effects like wheezing, exacerbation of asthma symptoms and other respiratory problems. Other studies are inconclusive or deny this correlation. This makes the association between PAR and airway hypersensitivity very controversial and still under debate. This work investigated if chronic treatment with PAR in rats could directly affect the contraction and relaxation for different stimulus in isolated airways. Rats were treated for 2 weeks with PAR (400 mg/Kg, v.o.). The blood was collected for biochemical analysis (alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBARs reaction and glutathione) and isolated tracheal rings were prepared in organ bath to measure isometric tone after contractile and relaxant stimulus. Hepatic enzymes (ALT, AST) and lipid peroxidation were increased after PAR-treatment, while glutathione was decreased. Rats do not present any alteration in airway myocytes responsiveness, either to contractile or relaxant stimulus (i.e. cholinergic agonist, membrane depolarization, Ca2+ influx across sarcolemma, internal Ca2+ release from sarcoplasmic reticulum, Ca2+ channel blocking, β-agonist and NOmediating relaxation). Despite increased oxidative stress and reduced antioxidant defense, chronic treatment with PAR does not induce airway hypersensitivity or risk of asthma in rats.


An interview with Senator David H. Pryor.
As Chairman of the Senate Special Committee on Aging, Sen. David H. Pryor (D-AR) is tackling the serious health care dilemmas facing senior citizens. In this interview with Nursing Economic+, Sen. Pryor offers his views on the urban-rural hospital differential, nursing home care, long-term care, and prescription drugs.


Coma in a premature infant associated with the transdermal absorption of propylene glycol.
A case of propylene glycol intoxication in a premature infant is reported. The infant went into a state of coma after treatment for burns with antiseptic dressings. Cessation of the topical treatment resulted in complete recovery. An exceptionally high level of the dressings' solvent, propylene glycol, found in the urinary chromatogram, was believed to be the causative agent. It is suggested that topical preparations containing propylene glycol should not be used in premature infants during the first weeks of life.


Reproductive function in male patients with type 1 diabetes mellitus.
This study was undertaken to evaluate conventional and some of the main bio-functional spermatozoa parameters, serum gonadal hormones and didymo-epididymal ultrasound features in patients with type 1 diabetes mellitus (DM1). DM1 affects an increasing number of men of reproductive age. Diabetes may affect male reproduction by acting on the hypothalamic-pituitary-testicular axis, causing sexual dysfunction or disrupting male accessory gland function. However, data on spermatozoa parameters and other aspects of the reproductive function in these patients are scanty. Thirty-two patients with DM1 [27.0 (25.0-30.0 years)] and 20 age-matched fertile healthy men [28.0 (27.25-30.75 years)] were enrolled. Patients with diabetic neuropathy, other endocrine disorders or conditions known to alter spermatozoa parameters were excluded. Each subject underwent semen analysis, blood withdrawal for fasting and post-prandial glycaemia, hormonal analysis and didymo-epididymal ultrasound evaluation before and after ejaculation. Patients with DM1 had a lower percentage of spermatozoa with progressive motility [10.0 (7.0-12.75) vs. 45.0 (42.0-47.75) %; p < 0.01] and a higher percentage of spermatozoa with abnormal mitochondrial function than controls [47.0 (43.0-55.0) vs. 2.0 (1.0-5.0) %; p < 0.01]. Patients also had greater post-ejaculatory diameters of cephalic [11.5 (10.2-13.6) vs. 6.0 (4.0-7.0) mm; p < 0.01] and caudal epididymis [5.5 (4.00-7.55) vs. 3.0 (2.0-4.0) mm; p < 0.01] compared to controls, suggesting a lack of the physiological post-ejaculation epididymal shrinkage. Correlation analysis suggested that progressive motility was associated with fasting glucose (r = -0.68; p < 0.01). The other parameters did not show any significant difference. Patients with DM1 had a lower percentage of spermatozoa with progressive motility, impaired mitochondrial function and epididymal post-ejaculatory dysfunction. These findings may explain why patients with DM1 experience fertility disturbance. Larger multi-centric studies are necessary to confirm these results.


Compartmentation of amino acid metabolism in the rat dorsal root ganglion; a metabolic and autoradiographic study.
The incorporation of radioactivity into glutamate, glutamine, GABA and other amino acids was followed after incubation of desheathed rat dorsal root ganglia in media containing [14C]glucose or [14C]acetate. The results indicated that [14C]glucose was incorporated into a large pool of glutamate, but that this glutamate pool did not synthesize glutamine or GABA to any great extent. [14C]Acetate, on the other hand, was incorporated into a small glutamate pool which was readily converted to glutamine, and which synthesized GABA to a greater extent than the large pool. Light microscopic autoradiography of ganglia incubated with [14C]glucose or [14C]acetate confirmed that the small pool labelled by acetate was probably associated with satellite glial cells, while the large pool was located within the ganglion neurons. The results are discussed within the context of previous work on compartmentation of glutamate metabolism in the central nervous system.


Palaearctic Egg Parasitoids Interaction to Three Grapevine Exotic Pests in Northwestern Italy: A New Association Involving Metcalfa pruinosa.
The most important exotic leafhopper pests currently affecting the Italian vineyards are the leafhoppers Scaphoideus titanus, Orientus ishidae and the planthopper Metcalfa pruinosa. Their highest population density is detected in the uncultivated areas with wild grapevines. Should these habitats be considered only a problem or a potential resource for Palearctic entomophagy of these three exotic pests? The aim of this work was to study the biotopes and biocoenosis present in the Piedmontese vineyard agroecosystem, evaluating the parasitization rate and other crucial aspects for a possible application in biological control. Several specimens of egg-parasitoid wasps were obtained from filed-collected two-year-old grapevine canes. The most prevalent one belonged to the Oligosita collina group (Trichogrammatidae) emerged only from M. pruinosa eggs with a parasitization rate of over 40%. The new association is the first report of such a high level of parasitization on the flatid planthopper. The parasitization rate mainly relied on the host egg density and the abundance of plants suitable for the oviposition. A second parasitoid generation on the overwintering eggs is discussed, as well as other hypothesis. Furthermore, the parasitization rate was higher than the one showed by the dryinid Neodryinus typhlocybae, the control agent introduced in Italy under the biological control strategy, highlighting a possible implication in this biocoenosis. We assume that the egg parasitoid adaptation may contribute to M. pruinosa control.


[Interkinetic migration of the auditory placode in the chick embryo].
Interkinetic nuclear migration was studied in cells forming the auditory placode of chick embryos with thymidine H3 and autoradiography. Our results show, that the nuclei in the auditory placode, synthesize D.N.A. in the outer zone, then migrate toward the inner zone to undergo division and subsequently return to the outer zone.


Fruits of Mimosa foliolosa (Fabales: Fabaceae) as sleeping shelter for Megachile (Pseudocentron) botucatuna (Hymenoptera: Megachilidae).
Several plant parts or organs are often used by insects for aggregation and even as resting areas. We first report the use of fruits of the legume Mimosa foliolosa pachycarpa as a night shelter for Megachile (Pseudocentron) botucana Schrottky (Hymenoptera: Megachilidae) in Serra do Cipó, southeastern Brazil. Only a single bee was found per fruit, in 86 fruits out of 1,003 fruits opened. The present findings augmented the occurrence of the phenomenon among bees, which is new to the harsh mountaintop environments in the Brazilian rupestrian fields.


Impact of xerostomia on dysphagia after chemotherapy-intensity-modulated radiotherapy for oropharyngeal cancer: Prospective longitudinal study.
The purpose of this study was to assess how xerostomia affects dysphagia. Prospective longitudinal studies of 93 patients with oropharyngeal cancer treated with definitive chemotherapy-intensity-modulated radiotherapy (IMRT). Observer-rated dysphagia (ORD), patient-reported dysphagia (PRD), and patient-reported xerostomia (PRX) assessment of the swallowing mechanics by videofluoroscopy (videofluoroscopy score), and salivary flow rates, were prospectively assessed from pretherapy through 2 years. ORD grades ≥2 were rare and therefore not modeled. Of patients with no/mild videofluoroscopy abnormalities, a substantial proportion had PRD that peaked 3 months posttherapy and subsequently improved. Through 2 years, highly significant correlations were observed between PRX and PRD scores for all patients, including those with no/mild videofluoroscopy abnormalities. Both PRX and videofluoroscopy scores were highly significantly associated with PRD. On multivariate analysis, PRX score was a stronger predictor of PRD than the videofluoroscopy score. Xerostomia contributes significantly to PRD. Efforts to further decrease xerostomia, in addition to sparing parotid glands, may translate into improvements in PRD. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1605-E1612, 2016.


Androgen deprivation therapy for precancerous lesions of the prostate.
Androgen deprivation therapy has become well-established in the treatment of prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) agonists, anti-androgens, orchiectomy, and combination hormonal therapy are treatment options offered to select patients. The prospect of intervention prior to the development of adenocarcinoma is appealing, and high-grade prostate intra-epithelial neoplasia (PIN), the only known precursor, is the best possible target. There is a decrease in the incidence of high-grade PIN in patients treated with combination androgen deprivation therapy (LHRH agonist and anti-androgen). Changes include increased apoptosis, decreased mitotic activity, less conspicuous nucleoli, and basal-layer prominence. Treatment with the 5alpha-reductase inhibitor finasteride results in a significant decrease in the incidence of high-grade PIN. The effect of 5alpha-reductase inhibitors and selective estrogen receptor modulators on histopathologic evaluation remains unclear, as the number of cases evaluated is small, but new data will be forthcoming with completion of multiple clinical trials.


Muscle-actuated power generator using cultured cardiomyocytes and PZT fiber.
A novel bio hybrid micro power generator using cardiomyocytes on a polymer wire is proposed. Cultured cardiomyocytes convert chemical energy into kinetic energy efficiently and beat themselves autonomously. PZT fiber was utilized for cell immobilized substrate and electro-mechanical coupling material. In this paper, two preliminary experimental results were shown to prove this principle.


Failure of a missing-fundamental complex to interact with masked and unmasked pure tones at its fundamental frequency.
Of interest here are the mechanisms underlying the extraction of temporal periodicities from complex acoustic stimuli. Two extreme versions of the underlying mechanisms are examined for possible psychophysical consequences, and experiments of two sorts are reported. In one, the detectability of a 200-Hz tone was measured in the presence, and the absence, of a tonal complex that gives rise to the experience of a missing fundamental having a pitch of 200 Hz in an attempt to see if the missing-fundamental waveform contributes to the masking of the tonal signal. We call this periodicity masking, but were unable to measure any, implying that if periodicity information was being used both to detect the signal and to perceive the missing fundamental, those two streams of afferent information are kept separate by the auditory nervous system, at least initially. In the second set of experiments, an "informational-masking" paradigm was used to introduce high uncertainty about the frequency of the tonal signal, and both detection and frequency discrimination were measured in the presence and absence of a missing-fundamental complex. This time the question was whether the periodicity information in the complex would produce a reduction in the frequency uncertainty about the signal and, thereby, improve performance. We call this possible effect periodicity cueing, but were unable to find evidence for its existence either. The failure to find either periodicity masking or periodicity cueing is discussed in regard to possible organizations of the auditory system, and in regard to the "periodicity-rate gap" seen in primary auditory fibers.


Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in differential diagnosis?
Serous papillary adenocarcinoma of the female genital organs and invasive micropapillary carcinoma of the breast have close histologic similarities. Thus, when these cancers occur synchronously or metachronously in the same patient, it is difficult to determine the primary site. We examined 23 serous papillary adenocarcinomas (16 ovarian, 5 endometrial, and 2 peritoneal) and 37 invasive micropapillary carcinomas of the breast (12 pure and 25 mixed types) on immunohistochemical expression of Wilm's tumor antigen-1 (WT1), CA125, and gross cystic disease fluid protein-15 (GCDFP-15), which have been reported to be useful in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary. The positive rates of WT1, CA125, and GCDFP-15 in serous papillary adenocarcinomas were 78%, 78%, and 0%, respectively, and the corresponding rates in invasive micropapillary carcinomas were 3%, 40%, and 38%. The CA125-positive rate of invasive micropapillary carcinoma was higher than the rate reported for other types of breast carcinomas. We consider CA125 to be not always useful in the differential diagnosis of serous papillary adenocarcinoma and invasive micropapillary carcinoma. Although the positive rate of WT1 was significantly higher in serous papillary adenocarcinoma than in invasive micropapillary carcinoma, WT1 expression in endometrial serous papillary adenocarcinoma was infrequent (20%). WT1 and GCDFP-15 could be useful markers for the differential diagnosis of ovarian and peritoneal serous papillary adenocarcinoma versus breast invasive micropapillary adenocarcinoma. However, the availability of GCDFP-15 is limited because of the low positive rate of GCDFP-15 in invasive micropapillary carcinomas.


Mosquito larvicidal potential of potash alum against malaria vector Anopheles stephensi (Liston).
Mosquito larviciding may prove to be an effective tool for incorporating into integrated vector management strategies for reducing malaria transmission. Here, we report the potential of potash alum, a traditionally known salt in Indian Ayurveda and Chinese medicine system, in malaria vector control by evaluating its aqueous suspension as larvicide and growth disruptor of Anopheles stephensi, under laboratory conditions. Immature stages of the mosquito were tested using WHO guidelines. 50 and 90% lethal concentrations among various larvae ranged between 2.1 to 48.74 ppm and 15.78 to 93.11 ppm, respectively. The results indicated that larvicidal effects of potash alum were comparable to various biological and chemical insecticides. The study provides considerable scope in exploiting local indigenous resources for the control of nuisance mosquito vectors.


Disaster Education: A Survey Study to Analyze Disaster Medicine Training in Emergency Medicine Residency Programs in the United States.
The increase in natural and man-made disasters occurring worldwide places Emergency Medicine (EM) physicians at the forefront of responding to these crises. Despite the growing interest in Disaster Medicine, it is unclear if resident training has been able to include these educational goals. Hypothesis This study surveys EM residencies in the United States to assess the level of education in Disaster Medicine, to identify competencies least and most addressed, and to highlight effective educational models already in place. The authors distributed an online survey of multiple-choice and free-response questions to EM residency Program Directors in the United States between February 7 and September 24, 2014. Questions assessed residency background and details on specific Disaster Medicine competencies addressed during training. Out of 183 programs, 75 (41%) responded to the survey and completed all required questions. Almost all programs reported having some level of Disaster Medicine training in their residency. The most common Disaster Medicine educational competencies taught were patient triage and decontamination. The least commonly taught competencies were volunteer management, working with response teams, and special needs populations. The most commonly identified methods to teach Disaster Medicine were drills and lectures/seminars. There are a variety of educational tools used to teach Disaster Medicine in EM residencies today, with a larger focus on the use of lectures and hospital drills. There is no indication of a uniform educational approach across all residencies. The results of this survey demonstrate an opportunity for the creation of a standardized model for resident education in Disaster Medicine. Sarin RR , Cattamanchi S , Alqahtani A , Aljohani M , Keim M , Ciottone GR . Disaster education: a survey study to analyze disaster medicine training in emergency medicine residency programs in the United States. Prehosp Disaster Med. 2017;32(4):368-373.


mTOR - Mediated protein synthesis by inhibiting protein catabolism in Chinese perch (Siniperca chuatsi).
Activation of the mechanistic target of rapamycin (mTOR) pathway is known to promote protein synthesis by enhancing mRNA translation. However, there have been few literatures on the effect of mTOR on protein metabolism in non-mammals. The main source of ammonia in fish comes from protein catabolism. The key step of protein catabolism involves the deamination and/or transamination of amino acids. This study is aimed to explore the mechanism underlying mTOR pathway influencing protein retention from the perspective of protein catabolism. Chinese perch were fasted for 24 h and divided into 4 groups randomly before intracerebroventricular (ICV) injection: (1) control group for leucine; (2) leucine group; (3) control group for leucine and rapamycin; (4) leucine and rapamycin group. Food intake was equivalent between each control and treatment groups at each time point (0.5, 4, 12 and 24 h post-injection). Ammonia-N excretion rate, blood glucose, S6 phosphorylation level, and expression of relative genes of protein catabolism (GDH, AMPD, AST, ALT) were determined. The results indicated that the pS6 level was increased, and that the ammonia-N excretion rate, blood glucose, and mRNA level of protein catabolism genes (GDH and AMPD) were significantly decreased after injection with leucine, while those changes were reversed after injection with leucine and rapamycin. Our study not only reveals the mechanism by which mTOR mediates protein synthesis by inhibiting protein catabolism in Chinese perch, but also provides reference for improving the utilization of feed protein.


Non-invasive diagnosis of acute rejection in renal transplant patients using mass spectrometry of urine samples - a multicentre phase 3 diagnostic accuracy study.
Reliable and timely detection of acute rejection in renal transplant patients is important to preserve the allograft function and to prevent premature allograft failure. The current gold standard for the rejection diagnosis is an allograft biopsy which is usually performed upon an unexplained decline in allograft function. Because of the invasiveness of the biopsy, non-invasive tests have been suggested to diagnose acute rejection including mass spectrometry analysis of urine samples. The aim of this study is to examine the diagnostic accuracy of mass spectrometry analysis in urine for the diagnosis of acute rejections using the biopsy as gold-standard. The study is an ongoing prospective, single-arm, multicentre, phase 3 diagnostic accuracy study. It started in October 2011 and will be concluded in December 2015. Patient within the first year after transplantation who are scheduled for a biopsy to clarify unexplained impairment of the allograft are consecutively recruited into the study. The overall sample size (n = 600) was calculated to demonstrate a sensitivity of 83 % and a specificity of 70 % for a one-sided type one error of 2.5 % and a power of 80 % per hypothesis. Biopsy evaluation and mass spectrometry analysis of urine samples (obtained immediately before biopsy) are performed independently by different readers without knowledge from the respective other assessment. The follow-up observation period is 6 months. For the primary analysis, the lower limits of the two-sided 95 % Wald confidence intervals for sensitivity and specificity will be compared with the pre-specified thresholds (83 % for sensitivity and 70 % for specificity). In secondary analyses the predictive values, the diagnostic measures in subgroups, and the clinical course will be assessed. Previous phase 2 diagnostic accuracy studies (in small selected study populations) provided sufficient evidence to suggest mass spectrometry on urine samples as a promising approach to detect acute rejections. This study determines the diagnostic performance of the test in the routine setting of post-transplant patient care, compared to the biopsy-based rejection diagnosis. The next step would be a randomized trial to compare the two diagnostic strategies (including the urine test or not) in relation to patient relevant endpoints. NCT01315067 ; March 14, 2011.


CD209a expression on dendritic cells is critical for the development of pathogenic Th17 cell responses in murine schistosomiasis.
In murine schistosomiasis, immunopathology and cytokine production in response to parasite eggs are uneven and strain dependent. CBA/J (CBA) mice develop severe hepatic granulomatous inflammation associated with prominent Th17 cell responses driven by dendritic cell (DC)-derived IL-1β and IL-23. Such Th17 cells fail to develop in low-pathology C57BL/6 (BL/6) mice, and the reasons for these strain-specific differences in APC reactivity to eggs remain unclear. We show by gene profiling that CBA DCs display an 18-fold higher expression of the C-type lectin receptor CD209a, a murine homolog of human DC-specific ICAM-3-grabbing nonintegrin, compared with BL/6 DCs. Higher CD209a expression was observed in CBA splenic and granuloma APC subpopulations, but only DCs induced Th17 cell differentiation in response to schistosome eggs. Gene silencing in CBA DCs and overexpression in BL/6 DCs demonstrated that CD209a is essential for egg-elicited IL-1β and IL-23 production and subsequent Th17 cell development, which is associated with SRC, RAF-1, and ERK1/2 activation. These findings reveal a novel mechanism controlling the development of Th17 cell-mediated severe immunopathology in helminthic disease.


Statin use and recurrence of atrial fibrillation after successful cardioversion.
Statins have important pleiotropic effects and have been shown to reduce vascular inflammation and the incidence of atrial fibrillation (AF) after cardiac surgery. The role of statins in patients with existing AF is poorly understood. We examined the effect of statins on recurrence of AF in patients after successful cardioversion. Statin use and documented recurrence of AF after successful cardioversion were evaluated in 625 patients with new onset AF who were followed prospectively in the Canadian Registry of Atrial Fibrillation. Logistic regression was used to model the effect of statin use on the recurrence of AF at 1 year while adjusting for potential confounders including concurrent medications. In a predominantly male population (62%) with median age 63 years, 12.3% were on statins at baseline. Overall, 32.5% had documented recurrence of AF at 1 year; 23.4% in patients on statins compared to 33.8% in those not on statins (P = .07). After adjustment for baseline differences and concomitant beta-blocker use, statin use was associated with a 74% reduction in AF recurrence, but only in statin users on beta-blockers (OR 0.26, 95% CI 0.10-0.66); statin users not on beta-blockers (OR 1.07, 95% CI 0.44-2.58). In an observational study of patients with new onset AF, statin use was associated with a significant 74% reduction in the odds of recurrent AF, but only in patients also taking beta-blockers. Importantly, statin without concomitant beta-blocker use was not associated with any changes in AF recurrence.


Neuroimaging: what neuroradiological features distinguish abusive from non-abusive head trauma? A systematic review.
To identify the evidence base behind the neuroradiological features that differentiate abusive head trauma (AHT) from non-abusive head trauma (nAHT). Systematic review. Literature search of 14 databases, websites, textbooks, conference abstracts and references (1970-February 2010). Studies had two independent reviews (three if disputed) and critical appraisal. Primary comparative studies of children <11 years old hospitalised with AHT and nAHT diagnosed on CT or MRI. Neuroradiological features that differentiated AHT from nAHT. 21 studies of children predominantly <3 years old were analysed. Subdural haemorrhages (SDH) were significantly associated with AHT (OR 8.2, 95% CI 6.1 to 11). Subarachnoid haemorrhages were seen equally in AHT and nAHT and extradural haemorrhages (EDH) were significantly associated with nAHT (OR for AHT 0.1, 95% CI 0.07 to 0.18). Multiple (OR 6, 95% CI 2.5 to 14.4), interhemispheric (OR 7.9, 95% CI 4.7 to 13), convexity (OR 4.9, 95% CI 1.3 to 19.4) and posterior fossa haemorrhages (OR 2.5, 95% CI 1 to 6) were associated with AHT. Hypoxic-ischaemic injury (HII) (OR 3.7, 95% CI 1.4 to 10) and cerebral oedema (OR 2.2, 95% CI 1.0 to 4.5) were significantly associated with AHT, while focal parenchymal injury was not a discriminatory feature. SDH of low attenuation were more common in AHT than in nAHT. Multiple SDH over the convexity, interhemispheric haemorrhages, posterior fossa SDH, HII and cerebral oedema are significantly associated with AHT and should be considered together with clinical features when identifying the condition.


Abnormalities of lexical and semantic processing in left temporal lobe epilepsy: an fMRI study.
We examined the efficiency of lexical and semantic processing and associated brain activation using functional magnetic resonance imaging (fMRI) in patients with left temporal lobe epilepsy (TLE). Twenty patients with left TLE (10 with hippocampal sclerosis, the HS group; and 10 with nonlesional MR scans, the NL group) and 12 healthy controls underwent an event-related fMRI analysis during a lexical decision task (LDT). Lexical and semantic processing were examined by comparing behavioral and imaging data associated with words and nonwords (lexicality) or with concrete and abstract words (concreteness). Although the control group showed greater activation associated with word stimuli than with nonword stimuli in a bilateral language network, both TLE groups showed greater activation for nonword stimuli than word stimuli, including greater activation of inferior frontal language areas (bilaterally in the HS group and left-lateralized in the NL group). The TLE groups also exhibited differential activation patterns during the processing of abstract and concrete words compared to controls, and compared to each other. For abstract words, in particular, the HS group showed activation of frontal areas typically associated with executive functions, whereas the NL group showed activation of more posterior semantic processing regions. These results suggest that left TLE is associated with altered functional organization of cortical networks involved in lexical and semantic processing. In addition, the organization observed varies as a function of hippocampal pathology.


A pilot study of the mistletoe and breast cancer (MAB) trial: a protocol for a randomised double-blind controlled trial.
A Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim is to add to this evidence base by initially testing the feasibility of a UK pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy. A mixed phase pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer (EudraCT number: 2018-000279-34). There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the mistletoe and breast cancer (MAB) therapies subcutaneously. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and 1 month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff. This trial is the first of its kind in the UK. Currently, mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy.


Forensic age determination of human inflicted porcine bruises inflicted within 10 h prior to slaughter by application of gene expression signatures.
Prediction-models based on gene expression profiles from experimental bruises are capable of determining the age of bruises with a precision of ±2 h. However, these models have not yet been applied on tissue from pigs in forensic cases requested by the police. We applied two prediction-models, based on mRNA expression of 13 (prediction-model no. 1) and 4 genes (prediction-model no. 2) involved in inflammation, on forensic cases of porcine bruises in order to determine if gene expression profiles can be used for age determination in forensic cases. Subcutaneous fat tissue from bruises notified to the police was sampled: 1) within 6 h after slaughter (group no. I, n = 142), and 2) after freezing the skin for up to 1 year (group no. II, n = 40). qPCR of genes involved in inflammation was performed to predict the bruise age after partial least squares analysis. mRNA expression data were obtained for 52.8% and 7.5% bruises in group nos. I and II, respectively. Prediction-model no. 2, based on the mRNA expression of Selectin E, Selectin P, Interleukin 6 and Nuclear Factor Kappa Beta Subunit1, was most suitable for predicting the age of bruises within 8 h prior to slaughter. In conclusion, mRNA expression profiles can assist in estimating the age of bruises. However, when applying gene expression signatures in forensic cases the age estimate should be interpreted together with histological manifestations. Subcutaneous tissue must be stabilized hours after the bruises are detected in order to obtain mRNA of a sufficient quality.


The effects of Clostridium difficile toxins A and B on membrane integrity and protein synthesis in intestinal cells in vivo and in vitro and in McCoy cells in vitro.
Clostridium difficile toxins A and B inhibited protein synthesis in McCoy tissue-culture cells but not in intestinal cells in vitro or in vivo. Toxins A and B had no effect on membrane permeability of either intestinal cells or McCoy cells.


Hepatitis B surface antigen prevalence among 12,393 rural women of childbearing age in Hainan Province, China: a cross-sectional study.
Hepatitis B virus (HBV) infection is highly endemic in China and it threats human health seriously. The hepatitis B surface antigen (HBsAg) prevalence among women of childbearing age plays an important role in mother to child transmission of HBV, as 30%~50% of chronic carriers can be attributed to maternal-infantile transmission. However, there are few studies which have reported on the prevalence of HBsAg among women of childbearing age in China. This study aimed to determine the prevalence of HBsAg and its associated risk factors among rural women of childbearing age in Hainan, which is the highest hepatitis B virus endemic province in China. A cross-sectional, population-based study, which included 12,393 rural women aged 15~49 years, enrolled by a multistage stratified cluster sampling, was carried out in Hainan province, China, from November 2007 to December 2008. Blood samples were obtained from each study participant, and screened for HBsAg. The overall HBsAg prevalence of childbearing age women was 9.51%. Risk factors for HBsAg positivity among rural women were: lower education level (OR=1.206), lower family monthly income (OR=1.233), having an HBsAg-positive family member (OR=1.300), without an immunization history (OR=1.243), tattooing (OR=1.190), body piercing (OR=1.293), vaginoscopy history (OR=1.103) and history of induced abortion (OR=1.142). There is a high HBsAg seroprevalence rate among rural women of childbearing age in Hainan province. Hence, it is necessary to take preventive measures to reduce the seroprevalence of HBsAg and to control its associated risk factors.


Analysis of analyte-receptor binding kinetics for biosensor applications: an overview of the influence of the fractal dimension on the surface on the binding rate coefficient.
An overview of fractal analysis is presented for analyte-receptor binding kinetics for different types of biosensor application. Data taken from the literature can be modelled by using (1) a single-fractal analysis, (2) a single- and a dual-fractal analysis, and (3) a dual-fractal analysis. Cases (2) and (3) represent a change in the binding mechanism as the reaction progresses on the surface. Predictive relationships developed for the binding rate coefficient as a function of the analyte concentration are of particular value because they provide a means by which the binding rate coefficients can be manipulated. Relationships are presented for the binding rate coefficients as a function of the fractal dimension, Df, or the degree of heterogeneity that exists on the surface. The binding rate coefficient is rather sensitive to the degree of heterogeneity, Df, that exists on the biosensor surface. For the examples analysed, the order of dependence of the binding rate coefficient on Df ranges from 1.4770 (k1), for the binding of intercalators and metabolites in solution to DNA immobilized at a positively charged surface, to 4.9434 for the binding of 5 nM nucleotide+GroEL in solution to GroES immobilized on a Ni2+-nitriloacetic acid sensor chip [Nieba, Nieba-Axmann, Persson, Hamalainen, Edebratt, Hansson, Lidholm, Magnusson, Karlsson and Pluckhun (1997) Anal. Biochem. 252, 217-228]. GroEl and GroES are two proteins (chaperones) which facilitate protein folding in the cell in an ATP-dependent manner [Hemmingson, Woolford, van der Vies, Tilly, Dennis, Georgopoulos, Henfrix and Ellis (1988) Nature (London) 333, 330-334]. The overview provides an overall analysis of the reaction parameters of importance observed and how they are influenced in antigen-antibody-binding kinetics for different biosensor applications. The predictive relationships presented provide further physical insights into the binding reactions on the surface, and should assist in enhancing biosensor performance. In general, the technique and the overview presented are applicable for the most part to other reactions occurring on different types of surface, for example cell-surface reactions.


Isolation and pathogenicity of porcine circovirus type 2 in mice from Guangxi province, China.
Porcine circovirus type 2 (PCV2), a member of the genus Circovirus and family Circoviridae, is a closed, small, circular, and single-stranded DNA virus, and it is a crucial swine pathogen of porcine circovirus-associated diseases (PCVADs). PCV2 was first detected in PK-15(ATCC-CCL) cells in 1974, which has caused significant economic loss to the swine industry throughout the world. And the first case of PCV2 was reported in China in 2000. At present, PCV2d is the main genotype circulating widely in China. Lymph samples were obtained from piglets with emaciation and respiratory disease in Guangxi province, China. The main pathogens were detected via PCR from lymph samples, and then PCV2-single positive samples were used to inoculate with PK-15 cells. After successive generations, the isolate was subsequently identified by polymerase chain reaction (PCR), immunofluorescence assay (IFA), Western blot (WB), and transmission electron microscopic (TEM). The full-length genome and genetic characterization of isolates were analyzed by Sanger sequencing. The TCID50 of the PCV2-GX-6 was determined by IFA, and the pathogenicity of PCV2 in BALB/c mice was analyzed via the mouse model. The isolates were successfully isolated from clinical samples. The complete genome of PCV2-GX-4, PCV2-GX-6, PCV2-GX-7, PCV2-GX-11 and PCV2-GX-16 have been amplified, sequenced, and deposited in GenBank (accession no.: OR133747, OQ803314, OR133748, OR133749, OR133750). Homology and phylogenetic analysis with reference strains showed that the isolates belonged to the PCV2d genotype. The PCV2-GX-6 could be stably passaged more than 30 times in PK-15 cells. PCV2-GX-6 was identified by PCR, IFA, WB and TEM. The results of homology showed that PCV2-GX-6 was closely related to the reference strains PCV2-JS17-8 (GenBank accession no.: MH211363). Pathogenicity studies in mice have shown that PCV2-GX-6 can lead to growth inhibition of mice. Meanwhile PCV2-GX-6 caused the typical lesions of spleen, lung and kidney. The results of qPCR showed that PCV2 can effectively proliferate in the liver, spleen, lung, and kidney. PCV2-GX-6 can successfully infect BLAB/c mice, effectively proliferate in major organs, and possessed high pathogenicity. In conclusion, combined with the genotype and pathogenicity of PCV2d currently prevalent, PCV2-GX-6 can be used as a candidate vaccine strain.


The significance of fluorescein angiography in the early diagnosis of lesions on ocular fundus at pseudoxanthoma elasticum patients.
The role of fluorescein angiography in early diagnosis of lesions on fundus of the eye at pseudoxanthoma elasticum patients has been shown. The authors show angiographic changes on the basis of three cases of pseudoxanthoma elasticum patients.


No beneficial effects of isocolloidoosmotic synthetic colloid addition to St. Thomas Hospital cardioplegic solution in ischemia-reperfusion injury in isolated perfused rat hearts.
1. Cardioplegic solutions provide the opportunity to operate on a nonbeating heart and to protect the heart against ischemic injury during cardiac surgery. The components of these solutions are constantly being modified in an effort to find the optimal solution. We studied the effects of colloidal volume replacers such as dextran, HES and gelatin as an isocolloidoosmotic addition to St. Thomas Hospital cardioplegic solution in ischemia-reperfusion injury of isolated rat hearts. 2. In the control group, after a stabilization period of 20 min, the hearts were arrested with St. Thomas Hospital cardioplegic solution for 3 min, then subjected to 30 min of global ischemia. Hearts then were reperfused for 10 min. In the experimental groups, the protocol was the same, but either HES 200/0.5 (50 g/L), modified fluid gelatin (30 g/l) or dextran 70 (25 g/L) were added to the St. Thomas Hospital solution. 3. All hearts were compared for their preischemic and postischemic contractility, heart rate, contractility rate product, coronary flow, lactate dehydrogenase, creatine phosphokinase enzyme leakage and wet/dry weight ratio. 4. All groups had similar contractility (for control, HES, gelatin and dextran groups the values at minute 10 of reperfusion were 59+/-9, 56+/-11%, 61+/-14%, 49+/-14% of initial values [P>0.05, respectively]) and enzyme leakage (lactate dehydrogenase 4.1+/-1.0, 8.1+/-1.5, 5.8+/-1.4, 3.7+/-1.2 [P>0.05] and for creatine phosphokinase 3.9+/-2.5, 6.4+/-3.7, 5.5+/-1.3, 5.5+/-0.8, P>0.05] IU xmin(-1) x g dry tissue(-1) in the reperfusion period, respectively) results as compared with the control group. 5. The addition of isocolloidoosmotic colloids to the cardioplegic solution did not appear to enhance the effectiveness of the crystalloid St. Thomas Hospital cardioplegic solution. If a colloid is to be chosen as a plasma replacer or an additive to priming solution in the preoperative period, or during open-heart surgery, it should be modified fluid gelatin-for no sign of cardiodepression was determined with the use of this agent.


The future perspectives of psychiatric neurosurgery.
The future of psychiatric neurosurgery can be viewed from two separate perspectives: the immediate future and the distant future. Both show promise, but the treatment strategy for mental diseases and the technology utilized during these separate periods will likely differ dramatically. It can be expected that the initial advancements will be built upon progress of neuroimaging and stereotactic targeting while surgical technology becomes adapted to patient-specific symptomatology and structural/functional imaging parameters. This individualized approach has already begun to show significant promise when applied to deep brain stimulation for treatment-resistant depression and obsessive-compulsive disorder. If effectiveness of these strategies is confirmed by well designed, double-blind, placebo-controlled clinical studies, further technological advances will continue into the distant future, and will likely involve precise neuromodulation at the cellular level, perhaps using wireless technology with or without closed-loop design. This approach, being theoretically less invasive and carrying less risk, may ultimately propel psychiatric neurosurgery to the forefront in the treatment algorithm of mental illness. Despite prominent development of non-invasive therapeutic options, such as stereotactic radiosurgery or transcranial magnetic resonance-guided focused ultrasound, chances are there will still be a need in surgical management of patients with most intractable psychiatric conditions.


Orientation of the manubrium mallei: inexplicably widely variable.
There is no consensus why the manubrium of the malleus, as viewed clinically through the external ear canal, generally points downward and posteriorly. To depict the alignment of the handle of the malleus, viewed clinically through the external auditory canal, relative to the zygomatic arch, the Frankfort plane, and a visual plane proxy and relative to the horizontal semicircular canal. Also, to assess bilateral symmetry and manubrium alignment relative to mastoid pneumatization. Postmortem anatomic dissection of 41 bequeathed adult crania without clinical otitis. The line of the manubrium as viewed through the external ear canal was measured relative to the Frankfort plane, to a proxy of the visual plane, and to the zygomatic arch. Mastoid sizes were determined radiographically. In a subset of 10 crania additionally studied by computed tomography, the manubrium position was checked relative to the horizontal semicircular canal. Relative to the zygomatic arch and Frankfort and visual planes, the range of manubrium angles was at least 45 degrees. Bilateral symmetry was found, each r 0.38 or greater (P < .05). Relative to the horizontal canals, the range of manubrial angles was 30 degrees, with symmetry suggested. Alignment did not correlate with mastoid pneumatization. Manubrium orientation as viewed through the external auditory canal is not obviously explicable. The wide variety of manubrium orientations may explain the manubrium-stapes offset that perplexes manubrium-stapes surgical constructions.


The outcome of untreated flexor pollicis longus rupture in patients with rheumatoid arthritis.
The aim of the study was to assess the natural history of untreated flexor pollicis longus (FPL) tendon rupture in patients with rheumatoid arthritis (RA). We reviewed a cohort of patients to assess the long-term effect of conservative management. We reviewed nine of 11 consecutive patients. We assessed objective outcomes including ranges of motion and strength and subjective outcomes including pain and function scores. We assessed seven women and two men. They had a mean age of 67 (range 48-82) years. Six of the nine patients had no more symptoms on the side of their FPL rupture than in the other thumb. Two were mildly more symptomatic and one much more symptomatic. Late thumb hyperextension did not appear to be a symptomatic problem. We recommend waiting at least 6 weeks before considering surgical reconstruction in patients who have an FPL rupture secondary to RA. The majority will recover so well that they may not choose reconstructive surgery. Level of evidence: IV.


Reporting of pressure ulcers and medical device related pressure ulcers in policy and practice: A narrative literature review.
Pressure ulcers (PUs) occur in a range of care settings, resulting in reduced quality of life for the individual. There has been a growing awareness that medical devices can cause PUs, although reporting has been limited. There is a need to evaluate PU reporting practice and identify whether standards exist for medical device-related pressure ulcers (MDRPUs). To synthesize academic and grey literature relevant to reporting of PUs and MDRPUs in healthcare settings. A systematic search of multiple scientific and grey literature databases was undertaken. Key search terms and Boolean operators were used to identify relevant literature. All sources of evidence discussing reporting practices were included in a synthesis. Primary topics are discussed in the corresponding analysis. Thirty-one evidence sources met the inclusion criteria, including 16 journal articles and 15 policy and guidance documents. The results revealed a variation in reporting practices. MDRPUs were often not identified as a separate category in local and national systems. Policies for related patient safety reporting varied across all organisational levels, with more serious categories of PUs reported more consistently. Reporting to medical device regulatory bodies was not mandatory. This narrative review identified inconsistencies in local and national reporting of PUs and MDRPUs, prohibiting meaningful comparisons and improvements in patient safety. Lack of specific medical device data and low levels of voluntary reporting to regulatory bodies is likely to result in an under-reporting, with little evidence of specific devices which may be a patient safety concern.


Effect of dietary protein level on platelet aggregation in rat.
In order to investigate the effects of dietary protein level on the development of atherosclerosis and arterial thrombosis, studies were made on platelet function, plasma lipids and aortic prostaglandin I2 biosynthesis in rats. Under the same calorie intake, the group consuming a low level of protein (10% casein) increased plasma triglycerides and platelet aggregability in comparison with control (20% casein) and high protein groups (60% casein). Moreover, the low protein group produced more thromboxane A2 and less prostaglandin I2 compared with the high protein one. These data suggest that high protein diets may have beneficial effects on arterial thrombosis.


Stress and burnout among healthcare professionals working in a mental health setting in Singapore.
International literature suggests that the experience of high levels of stress by healthcare professionals has been associated with decreased work efficiency and high rates of staff turnover. The aims of this study are to identify the extent of stress and burnout experienced by healthcare professionals working in a mental health setting in Singapore and to identify demographic characteristics and work situations associated with this stress and burnout. A total of 220 Singaporean mental health professionals completed a cross-sectional survey, which included measures of stress, burnout (exhaustion and disengagement), participants' demographic details, and working situation. Independent t-tests and one-way ANOVAs were used to examine between-group differences in the dependent variables (stress and burnout). Analyses revealed that healthcare professionals below the age of 25, those with less than five years experience, and those with the lowest annual income, reported the highest levels of stress and burnout. No significant differences were found with other demographic or work situation variables. Findings suggest that healthcare professionals working in a mental health setting in Singapore are experiencing relatively high levels of stress and burnout. It is important that clinicians, administrators and policy makers take proactive steps to develop programs aimed at reducing stress and burnout for healthcare professionals. These programs are likely to also increase the well-being and resilience of healthcare professionals and improve the quality of mental health services in Singapore.


Magnetic nanoantioxidants with improved radical-trapping stoichiometry as stabilizers for inhibition of peroxide formation in ethereal solvents.
Graphite-coated magnetic cobalt nanoparticles (CoNPs) decorated with hindered phenolic antioxidant analogues of 2,6-di-tert-butyl-4-methylphenol (BHT, E321) provided easily removable nanoantioxidants capable of preventing the autoxidation of organic solvents as tetrahydrofuran (THF).


Can gold and bitcoin hedge against the COVID-19 related news sentiment risk? New evidence from a NARDL approach.
The COVID-19 pandemic has led to extensive news coverage, causing investor sentiment to swing, which has further increased financial market price volatility. There is an increasing need to find a hedge against sentiment risk. This paper examines the hedge capabilities of gold and Bitcoin against COVID-19-related news sentiment (CNS) risk under a nonlinear autoregressive distributed lag (NARDL) model. Our empirical results reveal that there is an obvious asymmetric effect from the CNS on gold prices in the short run and that the decrease in the COVID-19-related news index would have a greater impact on gold prices than when it increases. The impact of CNS on Bitcoin prices is asymmetric in the long and short term, especially in the long term. In addition, we conclude that gold is a hedge against CNS risk in the long term, and the hedging effect of Bitcoin is mainly reflected in the short-term.


A new lignan from Pandanus tectorius.
A new lignan, named (8S, 8'S)-2,2',3,3'-tetramethoxy-4'-hydroxy-epoxylignan-4-O-β-D-glucoside (1), together with eight known compounds (2-9), was isolated from the leaves of P. tectorius. Their structures were elucidated on the basis of spectral characteristics and comparison with the data of literatures. Besides, the absolute configuration of 1 was established by using ECD calculations. The cytotoxicity of 1 in vitro against three selected tumor cell lines (A549, HeLa and MCF-7) was evaluated by MTT assay. The results showed that compound 1 exhibited moderate cytotoxicity against HeLa cell with IC50 value of 19.30 ± 4.46 μM.


γ-tubulin as a signal-transducing molecule and meshwork with therapeutic potential.
Knowledge of γ-tubulin is increasing with regard to the cellular functions of this protein beyond its participation in microtubule nucleation. γ-Tubulin expression is altered in various malignancies, and changes in the TUBG1 gene have been found in patients suffering from brain malformations. This review recapitulates the known functions of γ-tubulin in cellular homeostasis and discusses the possible influence of the protein on disease development and cancer.


Exploring the efficacy of tumor electric field therapy against glioblastoma: An in vivo and in vitro study.
Tumor electric fields therapy (TTFields) is emerging as a novel anti-cancer physiotherapy. Despite recent breakthroughs of TTFields in glioma treatment, the average survival time for glioblastoma patients with TTFields is <2 years, even when used in conjugation with traditional anti-cancer therapies. To optimize TTFields-afforded efficacy against glioblastoma, we investigated the cancer cell-killing effects of various TTFields paradigms using in vitro and in vivo models of glioblastoma. For in vitro studies, the U251 glioma cell line or primary cell cultures prepared from 20 glioblastoma patients were treated with the tumor electric field treatment (TEFT) system. Cell number, volume, and proliferation were measured after TEFT at different frequencies (100, 150, 180, 200, or 220 kHz), durations (24, 48, or 72 h), field strengths (1.0, 1.5, or 2.2V/cm), and output modes (fixed or random sequence output). A transwell system was used to evaluate the influence of TEFT on the invasiveness of primary glioblastoma cells. For in vivo studies, the therapeutic effect and safety profiles of random sequence electric field therapy in glioblastoma-transplanted rats were assessed by calculating tumor size and survival time and evaluating peripheral immunobiological and blood parameters, respectively. In the in vitro settings, TEFT was robustly effective in suppressing cell proliferation of both the U251 glioma cell line and primary glioblastoma cell cultures. The anti-proliferation effects of TEFT were frequency- and "dose" (field strength and duration)-dependent, and contingent on the field sequence output mode, with the random sequence mode (TEFT-R) being more effective than the fixed sequence mode (TEFT-F). Genetic tests were performed in 11 of 20 primary glioblastoma cultures, and 6 different genetic traits were identified them. However, TEFT exhibited comparable anti-proliferation effects in all primary cultures regardless of their genetic traits. TEFT also inhibited the invasiveness of primary glioblastoma cells in transwell experiments. In the in vivo rat model of glioblastoma brain transplantation, treatment with TEFT-F or TEFT-R at frequency of 200 kHz and field strength of 2.2V/cm for 14 days significantly reduced tumor volume by 42.63% (TEFT-F vs. control, p = 0.0002) and 63.60% (TEFT-R vs. control, p < 0.0001), and prolonged animal survival time by 30.15% (TEFT-F vs. control, p = 0.0415) and 69.85% (TEFT-R vs. control, p = 0.0064), respectively. The tumor-bearing rats appeared to be well tolerable to TEFT therapies, showing only moderate increases in blood levels of creatine and red blood cells. Adverse skin reactions were common for TEFT-treated rats; however, skin reactions were curable by local treatment. Tumor electric field treatment at optimal frequency, strength, and output mode markedly inhibits the cell viability, proliferation, and invasiveness of primary glioblastoma cells in vitro independent of different genetic traits of the cells. Moreover, a random sequence electric field output confers considerable anti-cancer effects against glioblastoma in vivo. Thus, TTFields are a promising physiotherapy for glioblastoma and warrants further investigation.


CA 125 in the diagnosis of pelvic masses.
CA 125 was measured preoperatively in 184 female patients presenting with pelvic masses. Ovarian tumors were diagnosed in 151 cases (91 carcinomas, eight borderline, 52 benign) and non-ovarian tumors in 33 (19 malignant, 14 benign). The sensitivity of CA 125 in identifying the malignant and borderline ovarian tumors was 86%, the specificity 78%; and the positive and negative predictive values 82% and 83%, respectively. Increased antigen values (greater than 35 U/ml) were observed in 63% of the non-ovarian malignant tumors. Considering only the diagnosis of malignancy in pelvic masses (ovarian plus non-ovarian malignant tumors) the specificity improved to 89% and the positive predictive value to 93%; the sensitivity and the negative predictive value decreased to 82% and 74%, respectively. CA 125 in the normal range (less than or equal to 35 U/ml) was observed both in ovarian and non-ovarian carcinomas. Therefore, preoperative CA 125 values in the normal range should be interpreted with caution. However, increased preoperative CA 125 levels in patients with pelvic masses are highly suggestive of a malignant tumor and CA 125 should be an adjunct to the preoperative diagnostic armamentarium.


Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice.
It remains unknown whether chronic circadian disturbance (CCD) during pregnancy can lead to mood disorders in the offspring. Here we show that pregnant mice in the F0 generation that were exposed to CCD stress displayed depression-like behaviors, and produced offspring in the F1 and F2 generations that also exhibited mood-associated behavioral phenotypes despite the lack of direct stressful experiences during their postnatal or adult period. Prenatal CCD stress was correlated with the elevation of plasma corticosterone levels in F1 mice. Furthermore, the diurnal expression profiles of core circadian clock genes were disrupted in the suprachiasmatic nucleus of F1 mice. Proteomics analysis revealed that prenatal CCD stress resulted in distinct changes in protein expression in the hypothalamus of female F1 mice, in particular proteins that were associated with cellular activities, metabolism, development and diseases. Sex-specific differences in melanocortin 4 receptor expression were apparent in the CCD F1 generation. We conclude that maternal exposure to chronic circadian disturbance during pregnancy can lead to sex-specific mood disorders that persist for at least two filial generations. The underlying mechanisms may depend on transgenerational changes in plasma corticosterone levels, circadian pacemaking, and hypothalamic protein expression.


Mutagenesis of the IS1 transposase: importance of a His-Arg-Tyr triad for activity.
Inspection of the primary sequence of the IS1 transposase suggested that it carries residues which are characteristic of the active site of integrases of the bacteriophage lambda family (Int). In particular, these include a highly conserved triad: His-Arg-Tyr. The properties of mutants made at each of these positions were investigated in vivo. The results of several different assays confirm that each is important for transposase activity. Moreover, as in the case of members of the Int family, different mutations of the His residue exhibited different effects. In a particular, His-to-Leu mutation resulted in complete inactivation whereas the equivalent His-to-Gln mutation retained low but significant levels of activity.


Negative regulation of the gene for H-2Kb class I antigen by adenovirus 12-E1A is mediated by a CAA repeated element.
Both positive and negative regulatory elements responsive to the product of the adenovirus type 12 E1A gene are located in the promoter region of the gene for mouse H-2Kbm1 major histocompatibility complex (MHC) class I antigen (1). We have analyzed the negative regulatory element that is affected by E1A and identified a target CAA repeated motif, CAA(A)CAAA, within -1725 to -1705 and -1591 to -1568 in a 316-bp sequence located in the far upstream region of H-2Kb promoter (-1837 to -1522; +1 refers to the cap site). The extent of cell surface expression of the MHC class 1 antigen was significantly decreased in the case of transfectants obtained by introducing an expression plasmid that included MHC class 1 cDNA with the CAA repeated element, as compared with that of a plasmid with mutated CAA repeats. We have also characterized the nuclear proteins that bind to this motif. The analysis of the effects of mutations during competition assays of in vivo and gel retardation competition assays demonstrated that the CAA repeated element is essential not only for E1A-dependent repression of transcription but also for the cell surface expression of the product of the mouse H-2Kb class I gene, presumably through nuclear proteins that specifically bind to it.


Neurocranial suture autotransplantation and periosteal dura stripping to provide a passive growth site in craniosynostosis--a case report.
The behaviour of a neurocranial suture autograft in a plagiocephalic infant is described. In a 7-month-old girl, born with right-sided unicoronal synostosis, part of the left-sided unicoronal suture was transplanted to the right-sided synostosectomy site. Also, in the pathological area, the periosteal 'layer' of the dura was surgically removed. The suture autotransplantation was integrated into the classical concept of radical remodelling, planned in a computer design environment. Growth of the suture was monitored by CT. Suture patency and osseous growth within the autograft could be demonstrated over a 1-year period. Neurocranial suture autotransplantation together with the prohibition of fusion-inducing dural signals seems to be a promising technique in the treatment of certain premature synostoses. This warrants a prospective clinical trial.


Impact of the Nucleosome Histone Core on the Structure and Dynamics of DNA-Containing Pyrimidine-Pyrimidone (6-4) Photoproduct.
The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion constituting a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with histones affects the lesion mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA-containing 64-PP within the nucleosome core particle by atomic-resolution molecular dynamics simulations and multiscale data analysis. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, the local DNA flexibility at the damaged site is enhanced due to imperfect structural adaptation to restraints imposed by the histone core. If 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent is deformed and exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails.


Preparation of chitosan/curdlan/carboxymethyl cellulose blended film and its characterization.
In this study, to improve the thermal and mechanical properties of chitosan films, a chitosan/curdlan/carboxymethyl cellulose (CS/CD/CMC) ternary blended film was prepared and characterized. To prepare a uniform CS/CD/CMC ternary blended film, an effective method of blending CD with other materials was established as the following conditions: the ternary solution temperature was maintained at 60 °C, and the pH was controlled in the range from 12 to 4. Compared to the pure chitosan, the CS/CD/CMC blended films exhibited better mechanical properties, permeability, and thermal stability. In addition, visible light properties of the ternary blending film were improved. Scanning electron microscope and Fourier transform-infrared spectroscopy analyses indicated good compatibility among the CS, CD and CMC, which led to a corresponding improvement in the properties owing to interactions among the three components in the blending process. So, an effective method of blending CD with CS and CMC was established, and the blending film has good thermal and mechanical properties.


Hirschsprung's disease: A bridge for science and surgery.
Understanding the true nature of the disease provided the basis for appropriate surgery for Hirschsprung's disease some 60 years ago. Nevertheless, surgical outcome remains unsatisfactory. Advances in diagnosis and treatment will depend on the elucidation of the pathogenesis and disease heterogeneity. This lecture outlines the author's attempt in the past 30 years to bridge some of the gaps of knowledge in Hirschsprung's disease. Studies of human fetal gut and aganglionic gut gave insight into the complexity of the human enteric nervous system, but the more fruitful studies came from genetic studies in which disease-causing genes were discovered, and the importance of noncoding mutations conferring disease susceptibility was unraveled. Animal models and pluripotent stem cell studies allowed elucidation of the interacting gene-cell-microenvironment signaling pathways for neural crest proliferation, migration, and differentiation. Hirschsprung's disease has been a bridge for science and surgery. An integrative approach could provide breakthroughs in the diagnosis and treatment strategies of this complex condition, leading to improved outcome.


Biliary and pancreatic obstruction during gallstone migration.
A prospective study on biliary and pancreatic obstruction during gallstone migration was performed in patients without acute pancreatitis. From January to October 1986, 125 patients with upper abdominal pain due to cholelithiasis were admitted to the hospital. Ultrasonography performed in all patients at admission demonstrated a distal bile duct measuring 7 mm or more in 39 patients, who were monitored for diameter changes of the biliary and pancreatic duct every 24 h and their stools screened for gallstones. Patients underwent surgery at least 8 days after admission. Gallstone migration was found preoperatively in 10 patients, of whom 6 had total serum bilirubin values lower than 2 mg/100 ml. Migration time was accurately determined by the sudden decrease in bile duct caliber. Simultaneous dilatation of biliary and pancreatic duct was found in 4 out of 10 patients with migrating gallstones and in 7 out of 23 patients without gallstone migration, though differences proved non-significant. Acute pancreatitis developed in 2 patients with lithiasis of the distal bile duct who ingested a fatty meal against medical advice. Gallstone migration, even of small stones, was preceded by a period of biliary obstruction. Pain and jaundice before migration were not as frequent as expected.


Psychological distress, comorbidities, and health behaviors among U.S. adults with seizures: results from the 2002 National Health Interview Survey.
To examine the association of seizures with health-related quality of life (HRQOL), physical and psychiatric comorbidities, and health behaviors. We analyzed data obtained from adults aged 18 years or older (n = 30,445) who participated in the 2002 National Health Interview Survey, an ongoing, computer-assisted personal interview of the noninstitutionalized U.S. population. An estimated 1.4% of adults 18 years or older reported being told by a health care professional that they had seizures. Persons with seizures were significantly more likely than those without seizures to report lower levels of education, higher levels of unemployment, pain, hypersomnia and insomnia, and psychological distress (e.g., feelings of sadness, nervousness, hopelessness, and worthlessness). In addition, they were significantly more likely to report insufficient leisure-time physical activity as well as physical comorbidities such as cancer, arthritis, heart disease, stroke, asthma, severe headaches, lower back pain, and neck pain. Our findings suggest that it is advisable for health care professionals to assess psychiatric and physical comorbidities among patients with a history of seizures potentially to improve patient health outcomes. Furthermore, public health surveillance systems should include questions on seizures, epilepsy, and mental health to better examine associations among these disorders and to better identify populations meriting further assessment and intervention.


Effect of food intake on the relative bioavailability of moclobemide (Ro 11-1163).
Twelve healthy adult volunteers received a single 100-mg tablet of moclobemide in an open-label crossover study designed to determine the influence of food on moclobemide absorption. Moclobemide was administered 30 min after a standard breakfast as well as under fasting conditions. Moclobemide absorption was rapid in the absence of food. Bioavailability parameters obtained when drug was taken 30 min after the meal suggested that the rate of absorption was slightly decreased in the presence of food (mean Tmax 0.71 h vs. 1.14 h), while the extent of absorption of moclobemide given with food was unaltered. The decreased absorption rate in the presence of food is not expected to be of clinical significance.


Clinical and dermoscopic patterns of melanocytic nevi in Hispanic adolescents: a descriptive study.
Melanocytic nevi are well-known, important precursors of melanoma among children and adults. The adolescence period is an important period for nevi formation and evolution. This study provides data of a longitudinal study of nevi in a Hispanic adolescent population. A cross-sectional survey and 1-year prospective follow-up study was performed on Hispanic students from grades 6 and 7 at a school in Caguas, Puerto Rico (n = 90). The survey was completed by the students and one of their parents. The backs of the children were clinically examined for melanocytic nevi using digital photography and dermoscopy. Follow-up was conducted one year later. The study cohort consisted of 53 (59%) boys and 37 (41%) girls, with an average age of 11.9 years (range 11-13 years). At the beginning of the study, 85% (n = 71/90) of the students presented with melanocytic nevi on their backs. After one year, new nevi were identified in 62% (n = 44/71), and there was a mean increase in nevus count of 1.8 (P < 0.001). A trend toward increased nevus count in lighter skin types was observed (P < 0.001). The predominant dermoscopic pattern was reticular (44%). The globular pattern was found most commonly in children with skin-type II (100%), while the reticular pattern was the most common among skin-types III (32%), IV (56%), and V (45%). This study supports the utility of digital photography and dermoscopy for the evaluation of melanocytic nevi, providing evidence of the interrelationship between nevus count, dermoscopic pattern, and skin phenotype.


Association between the serotonin transporter and cytokines: Implications for the pathophysiology of bipolar disorder.
Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD. Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay. SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1β, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD. While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD.


Rapid down-regulation of [3H]zolpidem binding to rat brain benzodiazepine receptors during flurazepam treatment.
In a previous study, it was found that down-regulation of benzodiazepine (BZ) binding in rats treated 4 weeks with flurazepam was relatively greater and more widespread when measured with [3H]zolpidem, a selective 'BZ1 receptor' ligand, than that measured with the non-selective ligand, [3H]flunitrazepam. In the present study, the time course for down-regulation of [3H]zolpidem binding was studied in rats treated with flurazepam. [3H]Zolpidem binding was also studied in rats given a midazolam treatment shown to cause tolerance. Rats were chronically treated with flurazepam for 1 or 2 weeks, or with midazolam for 3 weeks, then killed immediately after the treatment. Another group of rats was acutely treated with desalkyl-flurazepam and killed 30 min later. After 2 weeks of flurazepam treatment, the Bmax of [3H]zolpidem binding was decreased by 22% in cerebral cortex, 26% in cerebellum and 33% in hippocampus, with no change in the Kd in any region. After 1 week of flurazepam treatment, the Bmax was decreased by 23% in cerebellum and 14% in hippocampus, but not changed in cerebral cortex. The Kd was increased in cerebral cortex, but not in cerebellum or hippocampus. Neither the Bmax nor the Kd of [3H]zolpidem binding was affected by acute desalkyl-flurazepam treatment, or by 3 weeks of midazolam treatment. These results, in combination with previous findings, which showed no change in [3H]flunitrazepam binding after 1 or 2 week flurazepam treatment, and no change in cerebellum even after the 4 week treatment, may indicate a shift in BZ receptor subtypes in flurazepam-tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Preoperative magnetic resonance imaging-based breast volumetry for immediate breast reconstruction.
Preoperative breast magnetic resonance imaging (MRI) is a routine test for oncologic evaluation. However, determining breast volume using a preoperative MRI obtained as a part of oncologic evaluation has not yet been attempted for immediate breast reconstruction. The study introduces the benefit of MRI-based volumetry, not only in autologous breast reconstruction but also in implant-based breast reconstruction. Forty patients preparing for autologous breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap and 30 patients for implant-based breast reconstruction from June 2011 to June 2012 were included in this study. In every DIEP case, we collected data about actual resected breast tissue weight during mastectomy and final flap weight inserted intraoperatively. Computed tomography (CT) was for preoperative CT angiography for microsurgical breast reconstruction, whereas MRI was performed for oncologic evaluation. In every implant-based reconstruction case, MRI-based breast volume was measured in the same way for DIEP patients and resected breast tissue weight was measured intraoperatively. In addition, we also added or subtracted the breast volume by any modification, such as reduction and augmentation on the ipsilateral or contralateral side. To determine the accuracy of MRI-based volumetry, Pearson correlation coefficients were calculated to quantify the correlation between CT and MRI-based volumetry data and intraoperative volume measurements. For DIEP patients, the mean resected breast tissue weight during mastectomy was more closely related to the mean estimated breast volume using MRI than to the mean estimated breast volume using CT (Pearson coefficient 0.928 and 0.782; p = 0.001). MRI gave a closer correlation to final flap weight than CT (Pearson correlation coefficient 0.959 and 0.873; p = 0.001). For implant-based reconstruction patients, the breast volume measured by MRI correlated closely with the actual mean weight of resected breast specimens (0.937; p = 0.001). Mean net implanted volume was more closely related to mean estimated breast volume using MRI than to mean resected breast tissue weight during mastectomy (0.893 and 0.880; p = 0.001). Reliable volumetric information can be obtained using MRI for breast implant volume and autologous tissue needed in optimizing symmetry in breast reconstruction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Morphological progression of emphysema on thin-section CT: Analysis of longitudinal change in the number and size of low-attenuation clusters.
To evaluate morphological changes in the number and size of low-attenuation clusters on computed tomography (CT) in patients with emphysema. In 27 patients who had follow-up CT scans for 6 months or greater, initial 27 scans and follow-up 39 scans were analyzed. The number per slice (LAN/s) and mean size (LAS) of low-attenuation clusters less than -950 HU, and total low-attenuation area below -950 HU per slice (LAA-950/s) were calculated. LAS and LAA-950/s were significantly increased over time. No significant correlation was found between LAN/s and follow-up period. LAS increased in 37 of 39 (95%) follow-up scans, whereas LAN/s decreased in 17 of 39 (44%) follow-up scans. On the morphological progression of emphysema, the mean size of low-attenuation clusters was significantly increased during the follow-up period, whereas no significant correlation was found between the number of low-attenuation clusters and follow-up period.


Reduced novelty-P3 associated with increased behavioral distractibility in schizophrenia.
Behavioral and electrophysiological brain responses were used to examine the relationship between the vulnerability to distraction and the orienting response in schizophrenia. Nineteen schizophrenics and nineteen matched healthy controls were instructed to ignore task-irrelevant auditory stimuli while they classified capital letters and digits. The auditory sequences contained repetitive standard tones occasionally replaced by complex novel sounds. Relative to controls, patients showed an increased behavioral distraction, as indicated by a larger response time increase caused by novel sounds, and a disturbance in the attention orienting toward distracting stimuli, as indicated by a reduced novelty-P3. This behavioral-electrophysiological dissociation may stem from a limited pool of available resources. Thus, the few attentional resources directed toward novel stimuli would be sufficient to cause an important decrease of the similarly reduced amount of resources assigned to task-relevant stimuli, resulting in a striking impairment of the ongoing task performance.