Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles.
Nitric oxide (.NO) released by S-nitrosoglutathione (GSNO) inhibited enzymatic activities of rat heart mitochondrial membranes. Cytochrome oxidase activity was inhibited to one-half at an effective .NO concentration of 0.1 microM, while succinate- and NADH-cytochrome-c reductase activities were half-maximally inhibited at 0.3 microM .NO. Submitochondrial particles treated with .NO (either from GSNO or from a pure solution) showed increased O(-)(2) and H202 production when supplemented with succinate alone, at rates that were comparable to those of control particles with added succinate and antimycin. Rat heart mitochondria treated with .NO also showed increased H2O2 production. Cytochrome spectra and decreased enzymatic activities in the presence of .NO are consistent with a multiple inhibition of mitochondrial electron transfer at cytochrome oxidase and at the ubiquinone-cytochrome b region of the respiratory chain, the latter leading to the increased O2- production. Electrochemical detection showed that the buildup of a .NO concentration from GSNO was interrupted by submitochondrial particles supplemented with succinate and antimycin and was restored by addition of superoxide dismutase. The inhibitory effect of .NO on cytochrome oxidase was also prevented under the same conditions. Apparently, mitochondrial O2- reacts with .NO to form peroxynitrate and, by removing .NO, reactivates the previously inhibited cytochrome oxidase. It is suggested that, at physiological concentrations of .NO, inhibition of electron transfer, .NO-induced O2- production, and ONOO- formation participate in the regulatory control of mitochondrial oxygen uptake.


The lymph node revisited: development, morphology, functioning, and role in triggering primary immune responses.
Scenarios have been proposed to explain how lymphoid components of a lymph node favor the encounter of a drained antigen with a circulating competent naïve lymphocyte to trigger a primary immune response. However, these scenarios rest on incorrect concepts about the organ. This situation resulted from a loss of interest for studies on in vivo lymphoid organs due to a widespread switch, decades ago, to work on suspended lymphoid cells. However, an in vivo holistic study of the organ continued in our laboratory. The present review synthesizes resulting knowledge on lymph node morphology and global functioning. We show that the opening of an afferent lymphatic vessel into the subcapsular sinus is the focal point from which the related portion of a lymph node-a node compartment-is developed. As to the formation of a compartment's lymphoid components, it is neonatally orchestrated by the dichotomic nature and distribution of antigens in this subcapsular sinus, which determines a dichotomic recruitment of circulating cells and the compartment's architectural complexity. The transport process of an antigen from a given tissue territory into restricted sites of the draining compartment further defines its local morphological features and activities, while providing the possibility to reduce the wandering of a short-lived naïve cell through innumerable target-devoid sites. We also explain that the nodal lymphoid components are not implicated in the triggering of primary responses, but are rather products of such responses. Scenarios for the triggering of primary responses, consistent with real node morphology and functioning, are proposed.


Heavy Metal Pollution of Chari River Water during the Crossing of N'Djamena (Chad).
This study was carried out to identify and assess the water quality of the Chari River. The Chari, 1200 km long, is Chad's major water source. Municipal sewage, industrial wastewater discharge, and seasonal run-off from agriculture are regularly fed into the river. Several trace metals such as Cu, Zn, Fe, Ni, Cr, Mn, and Cd, were measured in different sampling stations located along the Chari River at N'Djamena in different campaigns from 2008 to 2010. Overall, manganese, zinc, chromium, and copper concentration levels were mainly in the range of the permissible limits prescribed by WHO guidelines (WHO 2011). Nickel, iron, and cadmium concentrations were still high. This preliminary study allowed us to identify the magnitude of toxic pollutants, which are responsible for Chari River water contamination in the study area. This study revealed that urgent measures must be taken to protect the local people from health problems resulting from high concentrations of heavy metals.


Evaluating the Viability of Neurocognition as a Transdiagnostic Construct Using Both Latent Variable Models and Network Analysis.
The relational structure of psychological symptoms and disorders is of crucial importance to mechanistic and causal research. Methodologically, factor analytic approaches (latent variable modeling) and network analyses are two dominant approaches. Amidst some debate about their relative merits, use of both methods simultaneously in the same data set has rarely been reported in child or adolescent psychopathology. A second issue is that the nosological structure can be enriched by inclusion of transdiagnostic constructs, such as neurocognition (e.g., executive functions and other processes). These cut across traditional diagnostic boundaries and are rarely included even though they can help map the mechanistic architecture of psychopathology. Using a sample enriched for ADHD (n = 498 youth ages 6 to 17 years; M = 10.8 years, SD = 2.3 years, 55% male), both approaches were used in two ways: (a) to model symptom structure and (b) to model seven neurocognitive domains hypothesized as important transdiagnostic features in ADHD and associated disorders. The structure of psychopathology domains was similar across statistical approaches with internalizing, externalizing, and neurocognitive performance clusters. Neurocognition remained a distinct domain according to both methods, showing small to moderate associations with internalizing and externalizing domains in latent variable models and high connectivity in network analyses. Overall, the latent variable and network approaches yielded more convergent than discriminant findings, suggesting that both may be complementary tools for evaluating the utility of transdiagnostic constructs for psychopathology research.


Signal-on Protein Detection via Dye Translocation between Aptamer and Quantum Dot.
A unique interaction between the cyanine dye and negatively charged quantum dot is used to construct a signal-on biaptameric quantum dot (QD) Förster resonance energy transfer (FRET) beacon for protein detection and distinct aptamer characterization. The beacon comprises a pair of aptamers, one intercalated with the cyanine dye (YOYO-3) and the other conjugated to a negatively charged, carboxyl-QD. When the target protein is present, structural folding and sandwich association of the two aptamers take place. As a consequence, YOYO-3 is displaced from the folded aptamer and transferred to the unblocked QD surface to yield a target concentration-dependent FRET signal. As a proof-of-principle, we demonstrate the detection of thrombin ranging from nanomolar to submicromolar concentrations and confirm the dye translocation using cylindrical illumination confocal spectroscopy (CICS). The proposed beacon provides a simple, rapid, signal-on FRET detection for protein as well as a potential platform for distinct aptamer screening.


Mincle is a long sought receptor for mycobacterial cord factor.
Mycobacterium tuberculosis is a leading killer worldwide, yet the adjuvancy of its cell wall has proven to be a valuable therapeutic tool for vaccination and immunotherapy. Much research effort has focused on the mycobacterial glycolipid trehalose-6,6'-dimycolate (TDM), a potent immunostimulant that is also known as cord factor. Now, the identification of the monocyte-inducible C-type lectin (Mincle) as an essential receptor for TDM provides new insight into the formation of the characteristic granulomas in tuberculosis and an avenue for rational adjuvant design.


Prevalence and antibiotic resistance of Salmonella Enteritidis and Salmonella Typhimurium in raw chicken meat at retail markets in Malaysia.
Salmonellosis is one of the major food-borne diseases in many countries. This study was carried out to determine the occurrence of Salmonella spp., Salmonella Enteritidis, and Salmonella Typhimurium in raw chicken meat from wet markets and hypermarkets in Selangor, as well as to determine the antibiotic susceptibility profile of S. Enteritidis and S. Typhimurium. The most probable number (MPN) in combination with multiplex polymerase chain reaction (mPCR) method was used to quantify the Salmonella spp., S. Enteritidis, and S. Typhimurium in the samples. The occurrence of Salmonella spp., S. Enteritidis, and S. Typhimurium in 120 chicken meat samples were 20.80%, 6.70%, and 2.50%, respectively with estimated quantity varying from <3 to 15 MPN/g. The antibiogram testing revealed differential multi-drug resistance among S. Enteritidis and S. Typhimurium isolates. All the isolates were resistance to erythromycin, penicillin, and vancomycin whereas sensitivity was recorded for Amoxicillin/Clavulanic acid, Gentamicin, Tetracycline, and Trimethoprim. Our findings demonstrated that the retail chicken meat could be a source of multiple antimicrobial-resistance Salmonella and may constitute a public health concern in Malaysia.


Wise-pattern breast reconstruction: modification using AlloDerm and a vascularized dermal-subcutaneous pedicle.
Immediate implant-based breast mound reconstruction offers many advantages over staged implant reconstruction techniques. For large volume breast reconstruction, a Wise-pattern skin resection may provide very good aesthetic results; however, the submuscular implant pocket is inadequate to cover the inferior pole of the breast. In this patient population, the risk of implant exposure from T-point breakdown is significant. We present our technique of Wise-pattern breast reconstruction using AlloDerm (LifeCell, Branchburg, NJ) and a vascularized dermal-subcutaneous pedicle (DSP) to augment the volume and quality of immediate breast implant coverage, particularly in the area of the T-point suture lines. We reviewed a series of 20 consecutive patients with large breasts who were treated with an immediate implant reconstruction of greater than 400 mL volume using the Wise-pattern with DSP. Preoperative and postoperative 3-dimensional surface scan studies were performed to evaluate breast symmetry. The average volume of breast reconstruction in this study group was 458 mL. T-point breakdown occurred in 5 patients (25%). These patients were treated with local wound care and healed with an excellent aesthetic result. None of these patients required implant removal, implant exchange, or operative debridement. Pre- and postoperative 3-dimensional surface scan analysis of these patients demonstrated comparable differences between the affected and unaffected sides in women undergoing immediate breast implant reconstruction when compared with a matched group of patients undergoing 2-stage breast reconstruction with tissue expanders. Wise-pattern skin-reducing mastectomy is an excellent strategy to provide an aesthetically pleasing, immediate implant breast reconstruction. This technique provides breast symmetry that is at least comparable to that of tissue expander-based, staged implant reconstructions. The reliability of the Wise-pattern technique is significantly improved with the addition of AlloDerm to the muscular pocket and a vascularized DSP to preserve the integrity of the reconstruction in the presence of T-point breakdown.


Coated-platelets retain amyloid precursor protein on their surface.
Coated-Platelets are a subset of platelets produced by dual-agonist activation with collagen plus thrombin and are characterized by strong retention of several procoagulant, alpha-granule proteins on the cell surface. In this report we demonstrate that coated-platelets also retain full-length amyloid precursor protein (APP) on their surface in contrast to the cleavage of APP in platelets activated with a single agonist. In addition, western blot analysis indicated that APP is derivatized during coated-platelet synthesis. We subsequently measured coated-platelet production in patients with Alzheimer's disease (AD). Twenty-two AD patients showed a wide distribution of coated-platelet values; however the least impaired AD patients produced coated-platelets at a level significantly above that of aged controls (41.0 +/- 9.9 vs. 28.7 +/- 11.4%; mean +/- 1SD; p = 0.017). These findings suggest that coated-platelets may be a model of aberrant APP processing in early AD patients.


A new microvertebrate assemblage from the Mussentuchit Member, Cedar Mountain Formation: insights into the paleobiodiversity and paleobiogeography of early Late Cretaceous ecosystems in western North America.
The vertebrate fauna of the Late Cretaceous Mussentuchit Member of the Cedar Mountain Formation has been studied for nearly three decades, yet the fossil-rich unit continues to produce new information about life in western North America approximately 97 million years ago. Here we report on the composition of the Cliffs of Insanity (COI) microvertebrate locality, a newly sampled site containing perhaps one of the densest concentrations of microvertebrate fossils yet discovered in the Mussentuchit Member. The COI locality preserves osteichthyan, lissamphibian, testudinatan, mesoeucrocodylian, dinosaurian, metatherian, and trace fossil remains and is among the most taxonomically rich microvertebrate localities in the Mussentuchit Member. To better refine taxonomic identifications of isolated theropod dinosaur teeth, we used quantitative analyses of taxonomically comprehensive databases of theropod tooth measurements, adding new data on theropod tooth morphodiversity in this poorly understood interval. We further provide the first descriptions of tyrannosauroid premaxillary teeth and document the earliest North American record of adocid remains, extending the appearance of this ancestrally Asian clade by 5 million years in western North America and supporting studies of pre-Cenomaninan Laurasian faunal exchange across Beringia. The overabundance of mesoeucrocodylian remains at the COI locality produces a comparatively low measure of relative biodiversity when compared to other microvertebrate sites in the Mussentuchit Member using both raw and subsampling methods. Much more microvertebrate research is necessary to understand the roles of changing ecology and taphonomy that may be linked to transgression of the Western Interior Seaway or microhabitat variation.


Investigating the Conformational Dynamics of a Y-Family DNA Polymerase during Its Folding and Binding to DNA and a Nucleotide.
During DNA polymerization, the Y-family DNA polymerases are capable of bypassing various DNA damage, which can stall the replication fork progression. It has been well acknowledged that the structures of the Y-family DNA polymerases have been naturally evolved to undertake this vital task. However, the mechanisms of how these proteins utilize their unique structural and conformational dynamical features to perform the translesion DNA synthesis are less understood. Here, we developed structure-based models to study the precatalytic DNA polymerization process, including DNA and nucleotide binding to DPO4, a paradigmatic Y-family polymerase from Sulfolobus solfataricus. We studied the interplay between the folding and the conformational dynamics of DPO4 and found that DPO4 undergoes first unraveling (unfolding) and then folding for accomplishing the functional "open-to-closed" conformational transition. DNA binding dynamically modulates the conformational equilibrium in DPO4 during the stepwise binding through different types of interactions, leading to different conformational distributions of DPO4 at different DNA binding stages. We observed that nucleotide binding induces modulation of a few contacts surrounding the active site of the DPO4-DNA complex associated with a high free energy barrier. Our simulation results resonate with the experimental evidence that the conformational change at the active site led by nucleotide is the rate-limiting step of nucleotide incorporation. In combination with localized frustration analyses, we underlined the importance of DPO4 conformational dynamics and fluctuations in facilitating DNA and nucleotide binding. Our findings offer mechanistic insights into the processes of DPO4 conformational dynamics associated with the substrate binding and contribute to the understanding of the "structure-dynamics-function" relationship in the Y-family DNA polymerases.


Pandemic influenza A (H1N1) 2009 outbreak investigation in Nepal.
The World Health Organization, on 24 April 2009, announced a Public Health emergency of international concern caused by a new influenza virus Pandemic Influenza A 2009. The objective of this study was to analyze the basic epidemiology and distribution of Pandemic Influenza A 2009 in order to understand the course of Pandemic Influenza A 2009 in Nepal. The analyses were based upon all confirmed and probable cases that consulted Avian Influenza Control Project and National Public Health Laboratory during 29 April 2009 to 21 September 2010. Out of total 739 suspected samples collected, Pandemic Influenza A 2009 was detected in 210 cases in different districts of Nepal. The majority of cases were from the urban settlement of Kathmandu valley, Chitwan and Kaski and among age group 11-30 years. The clinical attack rate for Influenza like illness (ILI) was 28.48%. There was no significant difference between the clinical presentation of ILI and confirmed cases of Pandemic Influenza A 2009. This study presented the investigation of outbreak that helped to inform the course of epidemic in affected population and therefore urge for public health interventions.


Ethanol-stimulated behaviour in mice is modulated by brain catalase activity and H2O2 rate of production.
Over the last few years, a role for the brain catalase-H(2)O(2) enzymatic system has been suggested in the behavioural effects observed in rodents after ethanol administration. This role seems to be related to the ability of cerebral catalase to metabolise ethanol to acetaldehyde using H(2)O(2)as a co-substrate. On the other hand, it has been shown that normobaric hyperoxia increases the rate of cerebral H(2)O(2) production in rodents in vivo. Thus, substrate-level changes could regulate brain catalase activity, thereby modulating the behavioural effects of ethanol. The aim of the present study was to assess if the enhancement of cerebral H(2)O(2) production after hyperoxia exposure results in a boost of ethanol-induced locomotion in mice. CD-1 mice were exposed to air or 99.5% O(2) inhalation (for 15, 30, or 45 min) and 0, 30, 60 or 120 min after this treatment, ethanol-induced locomotion was measured. The H(2)O(2)-mediated inactivation of endogenous brain catalase activity following an injection of 3-amino-1,2,4-triazole was used as a measure of the rate of cerebral H(2)O(2) production. Hyperoxia exposure (30 or 45 min) potentiated the locomotor-stimulating effects of ethanol (2.5 or 3.0 g/kg), whereas cocaine (4 mg/kg) or caffeine (15 mg/kg)-induced locomotion and blood ethanol levels were unaffected. Moreover, the results also confirmed brain H(2)O(2) overproduction in mice. The present results suggest that an increase in brain H(2)O(2) production potentiates ethanol-induced locomotion. Therefore, this study provides further support for the notion that the brain catalase-H(2)O(2) system, and by implication centrally formed acetaldehyde, plays a key role in the mediation of ethanol's psychopharmacological effects.


Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis.
Defining environmental factors responsible for development of autoimmunity in rheumatoid arthritis (RA) is critical for understanding mechanisms of disease initiation and propagation. Notably, a history of cigarette smoking has been implicated in the genesis of RA and is associated with worse disease outcomes. Antibodies to peptidylarginine deiminase 4 (PAD4) are also associated with more severe RA. A subset of patients who have PAD4 autoantibodies that cross-react with PAD3 (anti-PAD3/4) are at the highest risk for interstitial lung disease, and this risk is augmented by a history of cigarette smoking. It is unclear, however, if smoking is etiologically linked to the development of anti-PAD4 antibodies. Patients were included in this study if they had physician-diagnosed RA as well as DNA, serum, and a date-matched clinical assessment (n = 274). Anti-PAD4 and anti-CCP antibodies were measured by immunoprecipitation and ELISA, respectively; shared epitope (SE) status was determined by HLA-DRβ1 genotyping. Logistic regression analysis was used to evaluate associations of smoking with PAD4 antibodies, with adjustment for relevant demographic and clinical features. Stratified analyses by disease duration and shared epitope status were also performed. Anti-PAD4 antibodies were present in 25% of RA patients, with 50% of these individuals having anti-PAD3/4 cross-reactive antibodies. Anti-PAD4 antibodies were significantly associated with a longer disease duration, SE alleles, and anti-CCP antibodies. Importantly, there were no significant differences in smoking history between anti-PAD4 positive and negative groups in univariate analyses, stratified analyses, or multivariable models. However, an inverse relationship between smoking and anti-PAD4 antibodies was suggested by a lower prevalence of current smokers among patients with anti-PAD3/4 antibodies compared to antibody negative individuals (p = 0.04). Further, the lowest levels of anti-PAD4 antibodies were observed in current smokers (p = 0.14), and a significant association of SE and anti-PAD4 antibodies was only present among never smokers (p = 0.01). Smoking history was not associated with anti-PAD4 antibodies in patients with RA. The finding that anti-PAD4 antibodies were not associated with smoking suggests that other environmental factors may contribute to the development of autoimmunity to PAD4 in these patients.


A method to enable a bottlenose dolphin (Tursiops truncatus) to echolocate while out of water.
The study of site-specific brain activity associated with dolphin echolocation has been hampered by the difficulties inherent in administering radiolabels and performing medical imaging while a dolphin echolocates in an aquatic environment. To overcome these limitations, a system has been developed to allow a bottlenose dolphin to echolocate while out of the water. The system relies on a "phantom echo generator" (PEG) consisting of a Texas Instruments C6713 digital signal processor with an analog input/output daughtercard. Echolocation clicks produced by the dolphin are detected with a hydrophone embedded in a suction cup on the melon, then digitized within the PEG. Clicks exceeding a user-defined threshold are convolved with a target impulse response, delayed, and scaled before being converted to analog and transmitted through a sound projector embedded in a suction cup attached to the dolphin's lower jaw. Dolphin in-air echolocation behavior, inter-click intervals, and overall performance were analogous to those observed during comparable underwater testing with physical targets, demonstrating that the dolphin was indeed performing an echolocation task while out of water.


Influences of age and dietary restriction on gastrocnemius electron transport system activities in mice.
Alterations in the mitochondrial electron transport system (ETS) may contribute to aging. Dietary restriction (DR) provides a model to investigate retarded aging. ETS activities were measured in gastrocnemius from 10- and 20-month-old B6C3F1 female mice fed either ad libitum (AL) or DR diets (40% < AL). Older (26 month old) AL mice were studied for complex IV. Activities of complexes I, III, and IV decreased 54-74% from 10 to 20 months of age in AL mice. At 10 months, activities of complexes I, III, and IV were 33-64% lower in DR compared to AL mice. The Km for ubiquinol-2 of complex III increased 29% by 20 months of age in AL mice while no change occurred in DR mice. The Vmax of complex IV declined by 90% from 10 to 26 months of age in AL mice and this change was opposed by DR. Complex IV contains high- and low-affinity binding sites. The Km for high-affinity sites was not influenced by age or diet through 20 months; however, the Km was approximately twofold higher at 26 months in AL mice. The percentage of total binding sites which were of high affinity fell from 68% at 10 months in AL mice to 46% at 20 months and was even lower (33%) at 26 months. This value was 80% for DR mice at 10 and 20 months. These alterations with aging in mitochondrial ETS capacities may contribute to decreases in skeletal muscle function.


[Association of dystrophinopathy with facial-scapular-humeral dystrophy in the same family].
We present the association of a distrophinopathy with a case of facioscupulohumeral dystrophy in two individuals belonging to the same family. The discrepancy in the seric creatinphosphokinase (CPK) of the two patients together with certain clinical data suggests the possibility that it is a question of two different processes. This impression was confirmed later through dystrophine analysis and genetic examination techniques. This case drew attention to the vital need today to insist on a combination of genetic examinations and dystrophine analysis when diagnosing muscular dystrophies, thus avoiding mistakes derived from diagnostic assumptions made on the basis of antecedents in the family involving neuromuscular disorders and the consequences that this might have regarding vital prognosis and advice to the family. This is the first case of coincidental association of these two processes within one family that has so far come to our knowledge.


[Role of somatostatin in the management of upper gastrointestinal bleeding].
There exists a substantial basis of experimental and clinical data to support that somatostatin and its long acting synthetic analogue octreotide may be therapeutically efficacious either as primary or adjunctive therapy in subgroups of patients with upper gastrointestinal bleeding. It has been proposed that somatostatin represents the optimal drug treatment for acute variceal bleeding due to its efficacy, its simplicity of administration and its lack of significant side effects. It provides beneficial respite if endoscopic therapy cannot be performed immediately. Somatostatin also facilitates the performance of diagnostic and of non-pharmaceutic interventions. Despite strong theoretical evidence in support of the application of somatostatin to the control of acute nonvariceal gastrointestinal bleeding, clinical trials have yielded conflicting results.


Preventive effect and possible mechanisms of ultrashort wave diathermy on myogenic contracture in a rabbit model.
The purpose of this study was to determine the preventive effect of ultrashort wave diathermy on immobilization-induced myogenic contracture and to explore its underlying mechanisms. Forty-two rabbits were randomly assigned into control (Group C), immobilization (Group I, which was further divided into one week, Group I-1; two weeks, Group I-2; and four weeks, Group I-4, subgroups by the length of immobilization) and ultrashort wave prevention (Group U, which was further divided into one week, Group U-1; two weeks, Group U-2; and four weeks, Group U-4, by time of treatment) groups. Intervention effects were assessed by evaluating rectus femoris cross-sectional area (CSA), knee range of motion, and the protein levels for myogenic differentiation (MyoD) and muscle atrophy F-box (MAFbx-1) in the rectus femoris. Compared with those of Group C, in Groups I and U, total contracture, myogenic contracture, MyoD and MAFbx-1 levels were significantly elevated, and CSA was significantly smaller (p < 0.05). Compared with those of Group I at each time point, MyoD levels were significantly elevated, MAFbx-1 levels were significantly lower, CSA was significantly larger, and myogenic contracture was significantly alleviated in Group U (p < 0.05). In the early stages of contracture, ultrashort wave diathermy reduces muscle atrophy and delays the process of myogenic contracture during joint immobilization; the mechanism of this may be explained as increased expression of MyoD triggered by suppression of the MAFbx-1-mediated ubiquitin-proteasome pathway.


The Role of Lactic Acid on Wound Healing, Cell Growth, Cell Cycle Kinetics, and Gene Expression of Cultured Junctional Epithelium Cells in the Pathophysiology of Periodontal Disease.
Lactic acid (LA) is short-chain fatty acid, such as butyric acid and propionic acid, that is produced as a metabolite of lactic acid bacteria, including periodontopathic bacteria. These short-chain fatty acids have positive effects on human health but can also have negative effects, such as the promotion of periodontal disease (PD), which is caused by periodontal pathogens present in the gingival sulcus. PD is characterized by apical migration of junctional epithelium, deepening of pockets, and alveolar bone loss. Thus, the junctional epithelial cells that form the bottom of the gingival sulcus are extremely important in investigating the pathophysiology of PD. The aim of this study was to investigate the effect of LA on wound healing, cell growth, cell cycle kinetics, and gene expression of cultured junctional epithelium cells. The results showed that stimulation with 10 mM LA slowed wound healing of the junctional epithelial cell layer and arrested the cell cycle in the G0/G1 (early cell cycle) phase, thereby inhibiting cell growth. However, cell destruction was not observed. LA also enhanced mRNA expression of integrin α5, interleukin (IL)-6, IL-8, intercellular adhesion molecule-1, and receptor activator of nuclear factor kappa-B ligand. The results of this study suggest that stimulation of junctional epithelial cells with high concentrations of LA could exacerbate PD, similarly to butyric acid and propionic acid.


Assessment of cerebral embolism and vascular reserve parameters in patients with carotid artery stenosis.
Carotid artery stenosis can result in the brain tissue injury related to the intracranial aterial flow disturbances as well as microembolic complications. The choice of the proper therapy in patients with carotid artery stenosis, especially asymptomatic, remains still a significant clinical problem. The study aim was an assessment of the cerebral embolism and brain vascular reserve parameters in patients with carotid artery stenosis regarding the occurrence of the clinical symptoms, the degree of stenosis as well as plaque morphology. The study included 60 patients, with internal carotid artery stenosis. The degree of stenosis, the atherosclerotic plaque surface and morphology were assessed by the means of Duplex Doppler ultrasound. Cerebrovascular reactivity (vasomotor reactivity reserve test and Breath Holding Index) and monitoring of the microembolic signals (MES) were assessed with transcranial Doppler ultrasound examination (TCD). The vasoreactivity parameters were significantly lower in the group of patients with stenosis ≥70% and in patients with ulcerations on the plaque surface. Microembolic signals were recorded significantly more often in symptomatic patients; in patients with stenosis ≥70%; in patients with ulcerations on the plaque surface and those with hypoechogenic plaque structure. Microembolic signals in patients with symptomatic carotid stenosis are one of the ultrasound features of unstable carotid stenosis. Worse reactivity parameters of the cerebral arteries are associated with the presence of a large degree of carotid artery stenosis.


Heme oxygenase-1 gene therapy for prevention of vasospasm in rats.
Hemoglobin causes contraction of cerebral arteries and is also believed to cause vasospasm after subarachnoid hemorrhage (SAH). The goal in this study was to determine if overexpression of heme oxygenase-1 (HO-1), the principal enzyme involved in the metabolism of hemoglobin, would reduce contractions of cerebral arteries brought on by hemoglobin and decrease vasospasm after experimental SAH. Injection of adenovirus expressing HO-1 (Ad5HO-1) into the cisterna magna of rats produced a significant increase in expression of HO-1 messenger RNA, and protein and HO-1 activity in the basilar artery ([BA]; p < 0.05 for each measure compared with vehicle and/or control virus, according to analysis of variance or unpaired t-test). Injection of adenovirus expressing beta-galactosidase (Ad-betaGal) produced only mild, statistically nonsignificant increases. The HO-I immunoreactivity was localized to the BA adventitia after injection of Ad5HO-1 or Ad-betaGal. Injection of Ad5HO-1 and Ad-betaGal increased the baseline diameter of the BA (measured directly via a transclival window) and brainstem cerebral blood flow (CBF), measured by laser Doppler flowmetry, compared with vehicle. Contraction of the BA after addition of hemoglobin was significantly inhibited, reduction in brainstem CBF was significantly prevented, and carboxyhemoglobin concentration was significantly increased in rats injected with Ad5HO-1 compared with Ad-betaGal and vehicle. Vasospasm was significantly ameliorated in rats in which Ad5HO-1 was injected into the cisterna magna at the time of SAH in a double-hemorrhage model. These results show that overexpression of HO-1 inhibits arterial contractions induced by hemoglobin and can reduce vasospasm after experimental SAH.


Set-shifting and selective attentional impairment in alcoholism and its relation with drinking variables.
Individuals with chronic alcoholism show impairments in visual scanning, set-shifting and response inhibition abilities. To study the relationship between performance on tests of set-shifting and selective attention, and alcohol intake variables (duration of dependence, amount of alcohol intake, and duration of abstinence during the past year). In this cross-sectional, controlled study, inpatients from a tertiary care centre were selected. Thirty patients with alcohol dependence and 15 age-, sex- and education-matched normal controls were administered the Trail Making Test (TMT) and Stroop test to assess visual scanning, set-shifting and response inhibition abilities. The data were analysed using the chi(2) test, t test and ANOVA with post-hoc analysis. The patient group performed poorly on all measures of the tests. The duration of dependence and the amount of alcohol intake (during the past 1 year) were not found to significantly affect the performance on the 2 tests. The duration of abstinence during the past 1 year was significantly related to performance on the Stroop test with patients having a longer duration of abstinence showing lesser impairment. Patients with a fewer number of days of alcohol intake during the past 1 year show relatively better visual scanning, set-shifting and response inhibition abilities.


Performance of an etalon-stabilized tunable diode laser system.
A wavelength-stabilized tunable diode laser and a reflective optical system can produce fringe-free spectra with a noise level of 10(-5) absorbance units and a precision of 10(-5) cm(-1) in the wave-number scale.


A seasonal variation in breast cancer.
To demonstrate a seasonal variation in the detection of breast cancer in women diagnosed at St Marks Breast Centre, Auckland. Data on women diagnosed with breast cancer at St Marks Breast Centre from January 1992 till December 2001 were obtained from the computerised database. A total of 1760 women were diagnosed with breast cancer; 1584 were referred by their general practitioner and 176 self referred. The peak incidence of seasonal diagnosis was in spring (September, October, November) with 521 cases. The lowest incidence was in summer (December, January, February) with 375 cases. These findings were consistent annually from 1992 to 2001. There is a seasonal variation in the incidence of breast cancer similar to that noted in other studies. Our findings suggest that temporal factors and possible behavioural patterns may have a role in this seasonal variation.


Bioavailability of zinc in rats fed on tuna as a protein source in the diet.
The objective of this study was to investigate the dietary zinc bioavailability in diets containing raw, cooked, steamed, and canned tuna as a protein source in the diet, and to evaluate different means of preparation, as well as various storage periods of the canned tuna, which was prepared according to industrial standards. Sterilized oil-free canned tuna was also made. The biological assays used for the study of the zinc utilization were carried out on Wistar rats fed with semi-synthetic diets for 12 days varying only in the protein source, which was casein-methionine or tuna provided as follows: raw, cooked in brine, steamed, sterilized with or without soybean oil, canned and stored for one or three years. Body weight, food intake, faecal and urinary zinc excretion, and zinc content in rat liver were monitored. No modifications were shown in food efficiency when diets including tuna were used, compared with those values from the casein-methionine diet. Thus, final body weight results were similar in all groups tested. Dietary zinc absorption was enhanced by consuming a raw white tuna diet. This beneficial effect disappeared after steaming or cooking in brine, but it was slightly recovered after sterilization with oil and storage of the canned tuna. Animals fed on the diets including the oil-free canned tuna, showed two or three times higher faecal and urinary zinc excretion than those fed on casein and canned tuna stored for 0, 1 or 3 years, reaching a negative balance. A negative effect was therefore found in both dietary and endogenous zinc utilization due to the consumption of oil-free canned tuna.


Diagnostic accuracy of (68)Ga-DOTANOC PET/CT imaging in pheochromocytoma.
The purpose of the present study was to evaluate the diagnostic accuracy of (68)Ga-DOTANOC positron emission tomography (PET)/CT in patients with suspicion of pheochromocytoma. Data of 62 patients [age 34.3 ± 16.1 years, 14 with multiple endocrine neoplasia type 2 (MEN2)] with clinical/biochemical suspicion of pheochromocytoma and suspicious adrenal lesion on contrast CT (n = 70), who had undergone (68)Ga-DOTANOC PET/CT, were retrospectively analyzed. PET/CT images were analyzed visually as well as semiquantitatively, with measurement of maximum standardized uptake value (SUVmax), SUVmean, SUVmax/SUVliver, and SUVmean/SUVliver. Results of PET/CT were compared with (131)I-metaiodobenzylguanidine (MIBG) imaging, which was available in 40 patients (45 lesions). Histopathology and/or imaging/clinical/biochemical follow-up (minimum 6 months) was used as reference standard. The sensitivity, specificity, and accuracy of (68)Ga-DOTANOC PET/CT was 90.4, 85, and 88.7%, respectively, on patient-based analysis and 92, 85, and 90%, respectively, on lesion-based analysis. (68)Ga-DOTANOC PET/CT showed 100% accuracy in patients with MEN2 syndrome and malignant pheochromocytoma. On direct comparison, lesion-based accuracy of (68)Ga-DOTANOC PET/CT for pheochromocytoma was significantly higher than (131)I-MIBG imaging (91.1 vs 66.6%, p = 0.035). SUVmax was higher for pheochromocytomas than other adrenal lesions (p = 0.005), MEN2-associated vs sporadic pheochromocytoma (p = 0.012), but no difference was seen between benign vs malignant pheochromocytoma (p = 0.269). (68)Ga-DOTANOC PET/CT shows high diagnostic accuracy in patients with suspicion of pheochromocytoma and is superior to (131)I-MIBG imaging for this purpose. Best results of (68)Ga-DOTANOC PET/CT are seen in patients with MEN2-associated and malignant pheochromocytoma.


Adverse Human Health Impacts in the Anthropocene.
This commentary presents a summarized discussion of key findings and relevant ideas from previously published study, index analysis, and human health risk model application for evaluating ambient air-heavy metal contamination in Chemical Valley Sarnia (CVS). The CVS study provides previously unavailable data in the CVS area which evaluates the adverse effects on air quality due to nearby anthropogenic activities. The study provided an assessment of environmental pollutants, finding that carcinogenic and non-carcinogenic substances are present in trace quantities. The main findings of the study suggest that chronic exposure of humans to several contaminants identified in the area studied may lead to carcinogenic health effects, including cancer (such as nephroblastomatosis) as well as non-carcinogenic health effects, such as damage to the tracheobronchial tree. Children were found to have a significantly higher risk, that is, a higher hazard index: a value used to measure non-carcinogenic health risk from heavy metals identified in air samples collected during the research period from 2014 to 2017. This study quantified the influence of environmental contaminants, relative to human exposures and the consequence of developing nephroblastomatosis in the human population.


Acute Pancreatitis Induced Splenic Vein Thrombosis.
Acute inflammation of the pancreas, known as pancreatitis, can result in many complications ranging from acute distress respiratory syndrome to pancreatic necrosis. A relatively common vascular complication of pancreatitis is splenic vein thrombosis (SVT) due to intimal inflammation leading to platelet aggregation and thrombosis. The management of SVT with regard to anticoagulation (AC) might appear to be perplexing at first given the recommendation to withhold any sort of AC. Research studies have shown that these patients have an increased risk of gastrointestinal bleeding without AC. In this report, we discuss a case of hypertriglyceridemia-induced pancreatitis. During hospitalization, our patient complained of worsening abdominal pain with objective fevers and leukocytosis in which CT scan of the abdomen was significant for hemorrhagic pancreatitis with necrosis, acute SVT, and splenomegaly. The patient was managed conservatively with IV fluids, pain relief medications, and antibiotics.


Streamline pair selection for comparative flow field visualization.
Fluid dynamics simulation is often repeated under varying conditions. This leads to a generation of large amounts of results, which are difficult to compare. To compare results under different conditions, it is effective to overlap the streamlines generated from each condition in a single three-dimensional space. Streamline is a curved line, which represents a wind flow. This paper presents a technique to automatically select and visualize important streamlines that are suitable for the comparison of the simulation results. Additionally, we present an implementation to observe the flow fields in virtual reality spaces.


Rigidified Derivative of the Non-macrocyclic Ligand H4OCTAPA for Stable Lanthanide(III) Complexation.
The stability constants of lanthanide complexes with the potentially octadentate ligand CHXOCTAPA4-, which contains a rigid 1,2-diaminocyclohexane scaffold functionalized with two acetate and two picolinate pendant arms, reveal the formation of stable complexes [log KLaL = 17.82(1) and log KYbL = 19.65(1)]. Luminescence studies on the Eu3+ and Tb3+ analogues evidenced rather high emission quantum yields of 3.4 and 11%, respectively. The emission lifetimes recorded in H2O and D2O solutions indicate the presence of a water molecule coordinated to the metal ion. 1H nuclear magnetic relaxation dispersion profiles and 17O NMR chemical shift and relaxation measurements point to a rather low water exchange rate of the coordinated water molecule (kex298 = 1.58 × 106 s-1) and relatively high relaxivities of 5.6 and 4.5 mM-1 s-1 at 20 MHz and 25 and 37 °C, respectively. Density functional theory calculations and analysis of the paramagnetic shifts induced by Yb3+ indicate that the complexes adopt an unprecedented cis geometry with the two picolinate groups situated on the same side of the coordination sphere. Dissociation kinetics experiments were conducted by investigating the exchange reactions of LuL occurring with Cu2+. The results confirmed the beneficial effect of the rigid cyclohexyl group on the inertness of the Lu3+ complex. Complex dissociation occurs following proton- and metal-assisted pathways. The latter is relatively efficient at neutral pH, thanks to the formation of a heterodinuclear hydroxo complex.


Tetrahydrobiopterin deficiency increases neuronal vulnerability to hypoxia.
Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide synthases (NOS). The aim of the present work was to study whether BH4 deficiency affects the vulnerability of neurones in primary culture to hypoxia. Intracellular BH4 levels were depleted by pre-incubating neurones with 5 mm 2,4-diamino-6-hydroxypyrimidine (DAHP) for 18 h, after which cells were exposed for 1 h to normoxic or hypoxic conditions. Our results showed that whereas neurones were resistant to hypoxia-induced cellular damage, BH4 deficiency in neurones led to oxidative stress, mitochondrial depolarization, ATP depletion and necrosis after 1 h of hypoxia. Indeed, hypoxia specifically inhibited mitochondrial complex IV activity in BH4-deficient neurones. All these effects were counteracted when neuronal BH4 levels were restored by incubating cells with exogenous BH4 during the hypoxic period. Moreover, hypoxia-induced damage in BH4-deficient neurones was prevented when Nomega-nitro-l-arginine monomethyl ester (NAME), haemoglobin or superoxide dismutase plus catalase were present during the hypoxic period, suggesting that peroxynitrite might be involved in the process. In fact, BH4 deficiency elicited neuronal NO dysfunction, resulting in an increase in peroxynitrite generation by cells, as shown by the enhancement in tyrosine nitration; this was prevented by supplements of BH4, NAME, haemoglobin or superoxide dismutase plus catalase during hypoxia. Our results suggest that BH4 deficiency converts neuronal NOS into an efficient peroxynitrite synthase, which is responsible for the increase in neuronal vulnerability to hypoxia-induced mitochondrial damage and necrosis.


Antibodies in the renin-angiotensin system.
Antibody interactions with the endothelial cell membrane glycoprotein angiotensin-converting enzyme (Kininase II) in vivo exhibit features of aggregation and capping with resultant shedding similar to those events described in several in vitro isolated cell systems. Requirements for divalent ligand binding and participation of cytoskeletal elements are demonstrated in vivo as well. Persistence of antigen in immune complexes with complement interaction appear to be necessary to induce an inflammatory response. Abrogation of this response occurs when circumstances permit antigenic modulation with disappearance of the immune complex.


The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal.
The LMO2 oncogene causes a subset of human T cell acute lymphoblastic leukemias (T-ALL), including four cases that arose as adverse events in gene therapy trials. To investigate the cellular origin of LMO2-induced leukemia, we used cell fate mapping to study mice in which the Lmo2 gene was constitutively expressed in the thymus. Lmo2 induced self-renewal of committed T cells in the mice more than 8 months before the development of overt T-ALL. These self-renewing cells retained the capacity for T cell differentiation but expressed several genes typical of hematopoietic stem cells (HSCs), suggesting that Lmo2 might reactivate an HSC-specific transcriptional program. Forced expression of one such gene, Hhex, was sufficient to initiate self-renewal of thymocytes in vivo. Thus, Lmo2 promotes the self-renewal of preleukemic thymocytes, providing a mechanism by which committed T cells can then accumulate additional genetic mutations required for leukemic transformation.


Spatial and reversal learning in congeneric lizards with different foraging strategies.
Environmental demands that require intensive search for mates, food and nest sites are correlated with efficient spatial memory in many mammalian and avian species. This convergence of evidence has led to the view that spatial memory, and the neurological structures associated with it, have been selected in niches that require memory for the location of goal objects. Whether such evolutionary demands are also correlated with nonspatial abilities that require flexible use of associations similar to those required for spatial memory has not been well studied. In addition, correlations between niche types and the use of spatial or nonspatial memory have not been investigated in nonmammalian, nonavian taxa. In this study, we investigated the relationship between foraging strategies and performance on two tasks, one spatial and the other nonspatial, in congeneric lizard species: Acanthodactylus boskianus, an active forager that collects clumped sedentary prey, Acanthodactylus scutellatus, a sit-and-wait predator that collects distributed mobile prey. The two species did not differ in their performance of a spatial memory task, but A. boskianus, the active forager, performed better on the reversal of a visual discrimination, a nonspatial task. These findings question the generality of the spatial adaptation model for vertebrates. We present the pliancy hypothesis, which we developed to account for these results. Copyright 1999 The Association for the Study of Animal Behaviour.


Which patient reported outcome domains are important to the rheumatologists while assessing patients with rheumatoid arthritis?
Patient-reported outcomes (PROs) aid in rheumatoid arthritis (RA) management, but it is not well understood which measures would be most relevant to the rheumatologists for making treatment decisions. We recruited rheumatologists nationally to participate in moderated structured group teleconference discussions using the nominal group technique. Participants in each group generated lists of the elements from patient's history and signs that they use to make treatment recommendations for RA. Each participant then selected the three most important elements from the generated list. The results of each group were then combined and summarized. Twenty-five rheumatologists participated in 4 groups (group size ranged from 4 to 8) and 150 available ranking votes across all groups. The statements generated across the 4 groups were categorized into 13 topics (including symptoms, physical function, comorbidities, social aspects, physical findings, response to treatment, treatment adherence, pain management, side effects, tests, access to care, contraception, and organ involvement), 10 of which received ranking votes. Symptoms received the highest ranking (46% of votes), followed by physical function (16%), and physical findings (13%). Among the unranked topics, social aspects had the highest number of statements (8 statements). Rheumatologists highly valued patient-reported RA symptoms and physical function to inform their treatment decisions, even above objective data such as physical findings and test results. These results can guide the selection of validated PRO measures to assess these domains to inform the clinical care of patients with rheumatoid arthritis.


Percutaneous computerized tomography guided renal cryoablation using local anesthesia: pain assessment.
The administration of intravenous sedation during prone computerized tomography guided, percutaneous procedures has the potential for complications. We assessed the pain associated with computerized tomography guided, percutaneous renal cryoablation using straight local anesthesia. Patients were treated with cryoablation probes inserted into the renal tumor under computerized tomography guidance with local anesthesia. Patients were asked to rate the pain experienced during needle placement and cryoablation using a visual 10-degree pain score scale. Sedation was given when pain was greater than 7 or when requested by the patient. Parameters assessed were cardiopulmonary complications, the need for intravenous supplementation, the pain score during the procedure and the postoperative score. A total of 25 patients (30 tumors) underwent a total of 26 cryoablation sessions with only local anesthesia. Mean patient age +/- SD was 67 +/- 13 years (range 33 to 88). Average tumor and ice ball size was 2.1 +/- 0.7 (range 1.1 to 4.3) and 4.1 +/- 1.0 cm (range 2.6 to 5.9), respectively. The mean dose of 1% lidocaine was 43.89 +/- 24.97 ml (range 10 to 110). All procedures were completed in an average of 68.78 +/- 20.7 minutes (range 40 to 120). Vital signs were not significantly changed during the procedure. Successful completion of percutaneous computerized tomography guided cryoablation using local anesthesia was accomplished in 22 of the 26 sessions (84.62%) without sedation. Four patients required intravenous supplementation. Percutaneous computerized tomography guided cryoablation for renal tumors can be performed using local anesthesia with minimal discomfort in most patients.


Biomimetic Chiral Photonic Crystals.
Although it is well known that the amazing iridescent colors of the cuticle of beetles reflect the intricate nanoscale organization of bio-fibers, artificial inorganic materials with comparable optical responses have not yet been synthesized from abiotic nanoscale building blocks. Such materials could find broad applications, including in circular polarizers, to generate circularly polarized luminescence, or in lasers. Herein, we describe a general method for the fabrication of biomimetic chiral photonic crystals by Langmuir-Schaefer assembly of colloidal inorganic nanowires. We not only reproduced the intricate helical structure and circularly polarized color reflection observed in beetles, but also achieved the highest chiroptical activity with a dissymmetry factor of -1.6 ever reported for chiral inorganic nanostructures. More importantly, the programmable structural control based on the precise interlayer arrangement endows us with unprecedented freedom to manipulate the optical activity of as-fabricated chiral photonic crystals.


Reversible Temperature-Switching of Hydrogel Stiffness of Coassembled, Silk-Collagen-Like Hydrogels.
Recombinant protein polymers, which can combine different bioinspired self-assembly motifs in a well-defined block sequence, have large potential as building blocks for making complex, hierarchically structured materials. In this paper we demonstrate the stepwise formation of thermosensitive hydrogels by combination of two distinct, orthogonal self-assembly mechanisms. In the first step, fibers are coassembled from two recombinant protein polymers: (a) a symmetric silk-like block copolymer consisting of a central silk-like block flanked by two soluble random coil blocks and (b) an asymmetric silk-collagen-like block copolymer consisting of a central random-coil block flanked on one side by a silk-like block and on the other side a collagen-like block. In the second step, induced by cooling, the collagen-like blocks form triple helices and thereby cross-link the fibers, leading to hydrogels with a thermo-reversibly switchable stiffness. Our work demonstrates how complex self-assembled materials can be formed through careful control of the self-assembly pathway.


Echocardiographic features of left ventricular recess, cleft, diverticulum, and aneurysm: A systematic review.
A pouch protruding into the wall of the left ventricle (LV) may be either a recess, cleft, diverticulum, or aneurysm. Being aware of these anomalies is essential to make accurate diagnosis and guide management decisions. Standard multimodality imaging of the heart enables detailed characterizations of LV fissures and outpouchings. They often present as an incidental finding on echocardiography, and the clinical significance can be difficult to address. We provide an overview of echocardiographic features of LV recess, cleft, diverticulum, pseudoaneurysms/aneurysms, and non-compaction based upon review of the literature as well as present some relevant clinical cases from our echocardiography labs.


H1 and H2 receptors mediate postexercise hyperemia in sedentary and endurance exercise-trained men and women.
In sedentary individuals, H(1) receptors mediate the early portion of postexercise skeletal muscle hyperemia, whereas H(2) receptors mediate the later portion. It is not known whether postexercise hyperemia also presents in endurance-trained individuals. We hypothesized that the postexercise skeletal muscle hyperemia would also exist in endurance-trained individuals and that combined blockade of H(1) and H(2) receptors would abolish the long-lasting postexercise hyperemia in trained and sedentary individuals. We studied 28 sedentary and endurance trained men and women before and through 90 min after a 60-min bout of cycling at 60% peak O(2) uptake on control and combined H(1)- and H(2)-receptor antagonist days (fexofenadine and ranitidine). We measured arterial pressure (brachial auscultation) and femoral blood flow (Doppler ultrasound). On the control day, femoral vascular conductance (calculated as flow/pressure) was elevated in all groups 60 min after exercise (sedentary men: Delta86 +/- 35%, trained men, Delta65 +/- 18%; sedentary women, Delta61 +/- 19%, trained women: Delta59 +/- 23%, where Delta is change; all P < 0.05 vs. preexercise). In contrast, on the histamine antagonist day, femoral vascular conductance was not elevated in any of the groups after exercise (sedentary men: Delta21 +/- 17%, trained men: Delta9 +/- 5%, sedentary women: Delta19 +/- 4%, trained women: Delta11 +/- 11%; all P > 0.16 vs. preexercise; all P < 0.05 vs. control day). These data suggest postexercise skeletal muscle hyperemia exists in endurance trained men and women. Furthermore, histaminergic mechanisms produce the long-lasting hyperemia in sedentary and endurance-trained individuals.


Glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system of mice.
Induction of apoptosis by rabies virus (RV) has been reported to be associated with the expression of the glycoprotein (G), but inversely correlated with pathogenicity. To further delineate the association between the expression of the G and the induction of apoptosis, recombinant RVs with replacement of only the G gene were used to infect mice by the intracerebral route. Recombinant viruses expressing the G from attenuated viruses expressed higher level of the G and induced more apoptosis in mice than recombinant RV expressing the G from wild-type (wt) or pathogenic RV, demonstrating that it is the G gene that determines the level of G expression and, consequently, the induction of apoptosis. Likewise, recombinant viruses expressing the G from wt or pathogenic RV are more pathogenic in mice than those expressing G from attenuated RV, confirming the inverse correlation between RV pathogenicity and the induction of apoptosis. To investigate the mechanism by which induction of apoptosis attenuates viral pathogenicity, mice were infected with wt or attenuated RV by the intramuscular route. It was found that low doses of attenuated RV induced apoptosis in the spinal cord and failed to spread to the brain or produce neurological disease. On the other hand, apoptosis was not observed in the spinal cord of mice infected with the same doses of wt RV and the virus spread to various parts of the brain and induced fatal neurologic disease. These results suggest that glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system (CNS) of mice.


First Observation of an Acetate Switch in a Methanogenic Autotroph (Methanococcus maripaludis S2).
The transition from acetate production by a microorganism in its early growth phase to acetate re-uptake in its late growth phase has been termed acetate switch. It has been observed in several heterotrophic prokaryotes, but not in an autotroph. Furthermore, all reports hitherto have involved the tricarboxylic acid cycle. This study reports the first observation of acetate switch in a methanogenic autotroph Methanococcus maripaludis S2, which uses the Wolfe cycle for its anaerobic respiration. When grown in minimal medium with carbon dioxide as the sole carbon source, and either ammonium or dinitrogen as the sole nitrogen source, M. maripaludis S2 dissimilated acetate in the early growth phase and assimilated it back in the late growth phase. The acetate switch was more pronounced in the dinitrogen-grown cultures. We postulate that the acetate dissimilation in M. maripaludis S2 may serve as a metabolic outlet for the carbon overflow in the early growth phase, and the assimilation in the late growth phase may be due to the scarcity of the carbon source. Based on the primary and secondary protein structures, we propose that MMP0253 may function as the adenosine diphosphate (ADP)-forming acetyl-CoA synthetase to catalyse acetate formation from acetyl-CoA. To verify this, we produced MMP0253 via the ligation-independent cloning technique in Escherichia coli strain Rosetta (DE3) using pNIC28-Bsa4 as the vector. The recombinant protein showed catalytic activity, when added into a mixture of acetyl-CoA, ADP, and inorganic phosphate (Pi). The concentration profile of acetate, together with the enzymatic activity of MMP0253, shows that M. maripaludis S2 can produce acetate and exhibit an acetate switch.


Purification of hepatocyte couplets by centrifugal elutriation.
An initial preparation of rat hepatocytes containing approximately 30% couplets was enriched by centrifugal elutriation. Of the couplets loaded onto the elutriator, 87% were eluted at medium flow rates of 60 to 80 ml/min at a rotor speed of 1,100 rpm; cells eluted in this range maintained a viability of more than 95%. Peak fractions were enriched in couplets to 84.5% +/- 2.5%. After elutriation, couplets retained the ability to secrete fluorescent cholephiles into sealed canalicular vacuoles. The preparation can now be used in hepatobiliary and hepatotoxicity studies not possible with preparations in which they are minor components.


Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation.
The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model in patients undergoing alcohol septal ablation (ASA) and to compare its performance to previous models. A total of 844 ASA patients without prior SCD event were included. The primary endpoint was a composite of SCD and appropriate implantable cardioverter defibrillator (ICD) therapy, identical to the HCM Risk-SCD endpoint. A distinction between periprocedural (≤30 days) and long-term (>30 days) SCD was made to discern procedure-related adverse arrhythmic events caused by the ASA-induced myocardial infarction from long-term SCD risk. Twenty patients reached the SCD endpoint within the first 30 days. During a follow-up of 6.5 ± 4.2 years, another 46 patients reached the SCD endpoint. The predicted 5-year SCD risk according to the HCM Risk-SCD model was 5.1%, and the observed 5-year SCD risk was 4.0%. The C-statistics for the use of the HCM Risk-SCD model was 0.61 (P = 0.02), the C-statistics for the use of the 2003 American College of Cardiology/ESC guidelines was 0.59 (P = 0.051), and the C-statistic for the use of the 2011 American College of Cardiology Foundation/American Heart Association guidelines was 0.58 (P = 0.054). Maximal left ventricular wall thickness, syncope after ASA, and fulfilling the 2014 ESC recommendations for primary ICD implantation according to the HCM Risk-SCD model, respectively, predicted SCD during long-term follow-up. The HCM Risk-SCD model can be used for SCD prediction in patients undergoing ASA.


Mental health workers' ratings of the importance of the goals of a cooperative CMHC-state hospital screening-aftercare program.
Ratings of the importance of the goals of a pilot community mental health center (CMHC)-state psychiatric hospital cooperative program aimed at providing screening and aftercare were obtained from 214 mental health professionals. Respondents were employed at state hospitals, at CMHCs that were participating in the program, and at CMHCs that were not participating in the pilot cooperative program. Ratings of importance were found to differ across goals, between mental health workers of state hospitals and CMHCs, between participating and nonparticipating CMHCs, between professions, and as a function of distance between CMHCs and state hospitals. Implications of the findings for the evaluation of the success of a cooperative screening-aftercare pilot program are discussed.


Caspase activity is required for commitment to Fas-mediated apoptosis.
Recognition of the widespread importance of apoptosis has been one of the most significant changes in the biomedical sciences in the past decade. The molecular processes controlling and executing cell death through apoptosis are, however, still poorly understood. The ICE (Interleukin-1beta Converting Enzyme) family-recently named the caspases for cysteine aspartate-specific proteases-plays a central role in apoptosis and may well constitute part of the conserved core mechanism of the process. Potentially, these proteases may be of great significance, both in the pathology associated with failure of apoptosis and also as targets for therapeutic intervention where apoptosis occurs inappropriately, e.g. in degenerative disease and AIDS. However, this is only likely if caspase activity is required before commitment to mammalian cell death. Here, we have used both peptide inhibitors and crmA transfection to inhibit these proteases in intact cells. Our experiments show that selective inhibition of some caspases protects human T cells (Jurkat and CEM-C7) from Fas-induced apoptosis, dramatically increasing their survival (up to 320-fold) in a colony-forming assay. This suggests that dysfunction of some, but not all, caspases could indeed play a crucial part in the development of some cancers and autoimmune disease, and also that these proteases could be appropriate molecular targets for preventing apoptosis in degenerative disease.


Construction of scrA::lacZ gene fusions to investigate regulation of the sucrose PTS of Streptococcus mutans.
The scrA gene coding for sucrose EnzymeII of the phosphoenolpyruvate dependent phosphotransferase system previously isolated from Streptococcus mutans was fused in vitro to the promoterless lacZ' gene to monitor the expression of the scrA gene. The scrA::lacZ gene fusion was introduced back into S. mutans GS-5IS3 by two independent transformation procedures involving either linear or plasmid DNA to produce both scrA and scrA+ mutants. These mutants should prove useful for analyzing the regulation of sucrose transport in S. mutans.


A fragile balance: perturbation of GABA mediated circuit in prefrontal cortex generates high intraindividual performance variability.
High intraindividual performance variability is one of the most robust findings to emerge in cognitive-experimental research of attention deficit hyperactivity disorder (ADHD). Evidences from studies incorporating structural or functional human brain mapping methods indicate that this increased intraindividual variability is not simply a sequel of general brain dysfunction, but is likely related to the functioning of neural circuits that engage the prefrontal cortex, particularly the dorsolateral areas (dlPFC). In order to examine further the anatomical and pharmacological substrate responsible for this high intraindividual variability disorder, we injected GABA(A) antagonist (bicuculline) or GABA(A) agonist (muscimol) in the dlPFC of monkeys performing a reflexive oculomotor task. Here we show that, whereas GABA(A) agonist injection induced no or minimal impairments, injection of GABA(A) antagonist dramatically increased the intraindividual variability of saccade response time and of saccade spatial accuracy (amplitude and direction). Overall, this study demonstrates that the balance between excitatory/inhibitory activities in the dlPFC is fragile but crucial, since local micro-injection of GABA(A) antagonist can induce marked behavioural effects. It also reveals that higher cognitive areas such as the dlPFC are markedly capable to influence the productions and metrics of reflexive movements. Altogether, this study provides promising perspectives for the development of new therapeutic strategies for the treatment of diseases in which high intravariability disorders are a prominent feature.


Acoustic phonetics in a clinical setting: a case study of /r/-distortion therapy with surgical intervention.
Acoustic measures are used to document the speech of a 6-year-old child with persistent /r/-distortion through several treatment interventions. The child originally presented a complex of speech disorders and was treated by a speech-language pathologist using phonological process techniques. The procedures successfully corrected most of his speech problems, although /r/ remained severely distorted. The primary acoustic manifestation of this distortion was a high third formant. Surgical correction of a banded lingual frenulum, along with adenoton-sillectomy indicated for sleep apnea, is shown to have had a small effect in lowering the third formant. A dramatic change was seen on reintroduction of therapy, when an extreme drop in third formant frequencies for /r/ was observed. The acoustic data are interpreted using speaker-internal controls derived from a dialect-appropriate adult model.


Saliency affects feedforward more than feedback processing in early visual cortex.
Early visual cortex activity is influenced by both bottom-up and top-down factors. To investigate the influences of bottom-up (saliency) and top-down (task) factors on different stages of visual processing, we used transcranial magnetic stimulation (TMS) of areas V1/V2 to induce visual suppression at varying temporal intervals. Subjects were asked to detect and discriminate the color or the orientation of briefly-presented small lines that varied on color saliency based on color contrast with the surround. Regardless of task, color saliency modulated the magnitude of TMS-induced visual suppression, especially at earlier temporal processing intervals that reflect the feedforward stage of visual processing in V1/V2. In a second experiment we found that our color saliency effects were also influenced by an inherent advantage of the color red relative to other hues and that color discrimination difficulty did not affect visual suppression. These results support the notion that early visual processing is stimulus driven and that feedforward and feedback processing encode different types of information about visual scenes. They further suggest that certain hues can be prioritized over others within our visual systems by being more robustly represented during early temporal processing intervals.


Thermal Modeling of the Port on a Refining Furnace to Prevent Copper Infiltration and Slag Accretion.
Fire refining of blister copper is a singular process at very high temperatures (~1400 K), which means the furnace is exposed to heavy thermal loads. The charge is directly heated by an internal burner. The impurities in the charge oxidize with the flux of hot gases, creating a slag layer on the top of the molten bath. This slag is periodically removed, which implies liquid metal flowing through the furnace port. To address its malfunction, a re-design of the furnace port is presented in this work. Due to the lack of previous technical information, the convective heat transfer coefficient between the slag and the furnace port was characterized through a combination of an experimental test and a three-dimensional transient model. Finally, the original design of the furnace port was analyzed and modifications were proposed, resulting in a reduction of the average temperature of the critical areas up to 300 K. This improvement prevents the anchoring of the accretion layer over the port plates and the steel plate from being attacked by the copper.


Biodegradable self-reinforced polyglycolic acid spiral stent in prevention of postoperative urinary retention after visual laser ablation of the prostate-laser prostatectomy.
The efficacy and safety of a new biodegradable (self-reinforced polyglycolic acid) spiral stent in securing free voiding despite edema after visual laser ablation of the prostate were studied. A biodegradable spiral stent was inserted into the prostatic urethra in 22 patients immediately after visual laser ablation of the prostate. Uroflowmetry, measurement of residual urine volume, urine culture, cystoscopy and assessment of symptomatic improvement were done before, and 1, 3 and 6 months after visual laser ablation of the prostate. All 22 patients voided freely on day 1 or 2 after visual laser ablation of the prostate. However, 4 patients later had urinary retention due to a short spiral or too rapid spiral degradation. Half of the patients experienced a transient decrease in flow with some obstructive symptoms at 3 weeks that lasted 1 to 2 weeks. At 4 weeks all spirals were degraded and 3 patients had a positive urine culture. The maximum flow rate increased and the residual urine volume decreased significantly concomitantly with significant symptomatic improvement. The self-reinforced polyglycolic acid spiral stent can effectively and safely prevent postoperative urinary retention after visual laser ablation of the prostate.


Effects of light quantity and quality on the decarboxylation of malic Acid in crassulacean Acid metabolism photosynthesis.
The rate of malic acid consumption in the Crassulacean acid metabolism (CAM) plant Kalanchoë daigremontiana Hamet et Perrier was found to be more rapid than the rate of photosynthetic oxygen evolution under all levels of irradiation by white light. This accounts for the accumulation of carbon dioxide in CAM tissues in the light.Action spectra of malate consumption and photosynthetic oxygen evolution in Kalanchoë were similar. Experiments using monochromatic photosynthetically active light in addition to a range of narrow waveband irradiations demonstrated that malic acid consumption in the experiments from which the action spectrum of acid consumption was constructed was not limited by the rate of photosynthesis. These data indicate that light involved in the promotion of malate consumption in CAM is absorbed by the same pigments that absorb the light which powers photosynthesis.


[Evaluation of trigger finger operative treatment and quality of life improvement with PEM (Patient Evaluation Measure) questionnaire].
One of the most frequent couse of pain and function impairment of the hand is trigger finger. The treatment of this desease can be conservative or operative. The aim of this study was the evaluation of operative treatment and improvement of the quality of life after the procedure with PEM questionnaire. There were 50 patient included into evaluation, all of them were treated in Second Department of Surgery of the Jagiellonian University Medical College between 2008 and 2010. Patients evaluated the function of their hand before surgery and then 3 months and a year after the procedure. There were also the assessment of treatment satisfaction. We analised the results and observed significant improvement of hand function after the surgery and very high satisfaction with the treatment. 1. Surgery is a very effective treatment method of trigger finger. 2. It is quite simple procedure and followed by very few complications. 3. It allows to significantly improve hand function and early return to work. 4. It can be performed in the outpatient clinic, which considerably reduces the costs of treatment.


Role of ROS-Induced NLRP3 Inflammasome Activation in the Formation of Calcium Oxalate Nephrolithiasis.
Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.


In re the Adoption (Amendment) Bill 1987, 26 July 1988.
The President of Ireland referred to the Supreme Court the question whether Section 3 of the Adoption (Amendment) Bill was repugnant to family rights contained in Articles 41 and 42 of the Constitution. Section 3 authorizes a child of parents who were married to each other to be adopted under exceptional circumstances, i.e., when the parents have totally failed their duty to their child, when that failure arises from "physical and moral" reasons and continues for more than a year prior to application, and when such failure constitutes abandonment. The Court found the Bill constitutional. It held that, under Articles 40.3 and 42.5 of the Constitution, the rights of the child within the family could in extraordinary circumstances be supplied by placing a child in an alternative family, and that the preconditions set forth in the Bill were sufficient to protect the constitutional guarantees afforded to the family. After the Supreme Court reached its decision, this Bill was signed into law as the Adoption (Amendment) Act 1988.


Toll-like receptor 4 (TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia.
Toll-like receptors (TLRs) are signaling receptors in the innate immune system that is a specific immunologic response to systemic bacterial infection. We investigated whether cerebral ischemia induced by the middle cerebral artery occlusion (MCAO) for 2 h differed in mice that lack a functional TLR3, TLR4, or TLR9 signaling pathway. TLR4, but not TLR3 or TLR9, knock-out (KO) mice had significantly smaller infarct area and volume at 24 h after ischemia-reperfusion (I/R) compared with wild-type mice. In addition, TLR4 KO mice improved in neurological deficits after I/R compared with wild-type mice. Moreover, we investigated the expression of TLR4 in the ischemic brain with immunohistochemistry. The number of TLR4-positive cells gradually increased from 1 h after MCAO to 22 h after I/R. We also examined the localization of TLR4 in the ischemic area. TLR4 was localized with CD11b-positive microglial cells in the ischemic striatum and the number of CD11b-positive microglial cells was smaller in TLR4 KO mice than in wild-type mice. In addition, we investigated the translocation of NF-κB among TLR3, 4, and 9 KO mice after I/R injury using western blotting. NF-κB's p65 subunit was decreased in TLR4 KO mice compared to wild-type mice, but not TLR3 or 9 KO mice. These data suggest that TLR4 knockout, but not TLR3 or TLR9 knockout, may play a neuroprotective role in ischemic brain injury induced by MCAO in mice.


The effect of o6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) status on the sensitivity to alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea(ACNU) in gallbladder carcinoma cells.
The aim of this study was to correlate O6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) expression in gallbladder carcinoma cells with drug sensitivity to the bifunctional alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Using 5 gallbladder carcinoma cell lines and 1 colon carcinoma cell line (SW48), the MGMT and hMLH1 status was assessed both by RT-PCR and Western blot analyses. Sensitivity to ACNU was estimated by the MTT assay. MGMT+/hMLH1+ status was revealed in 2 gallbladder carcinoma cells, MGMT-/hMLH1+ in another 3 gallbladder carcinomas and MGMT-/hMLH1- in SW48. MGMT-/hMLH1+ and MGMT-/hMLH1- cells were more sensitive to ACNU compared with MGMT+/hMLH1+ cells. These results indicate that MGMT, but not hMLH1, expression is an important determinant for drug sensitivity to ACNU in gallbladder carcinoma cells. The drug effect of ACNU, which depends on the MGMT status, was verified using xenograft tumors grown in nude mice. Furthermore, the apoptotic index of MGMT- GB-dl xenografts was significantly increased by ACNU treatment, compared with that of MGMT+ KMG-C. In conclusion, the sensitivity to ACNU was not associated with hMLH1 status, but was found to depend only on the MGMT status. ACNU might be a useful chemotherapeutic agent for MGMT- gallbladder carcinoma, which is associated with poor patient outcome.


Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.
Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to the etiology of many diseases, including neurodegenerative diseases (NDDs) such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, Multiple sclerosis, and Parkinson's diseases. In addition, oxidative stress causing protein misfold may turn to other NDDs include Creutzfeldt-Jakob disease, Bovine Spongiform Encephalopathy, Kuru, Gerstmann-Straussler-Scheinker syndrome, and Fatal Familial Insomnia. An overview of the oxidative stress and mitochondrial dysfunction-linked NDDs has been summarized in this review.


miR-877-5p antagonizes the promoting effect of SP on the gastric cancer progression.
Gastric cancer is one of the four major tumors in the world and the second leading cause of cancer-related death. It was reported that Substance P (SP), as an oncogenic factor, could regulate the expression of miRNAs in gastric cancer progression. Here, we focused on the role of miR-877-5p in gastric cancer development and the miR-877-5p involvement in the SP-mediated gastric cancer development. The mRNA expression level and cell proliferation were assessed by quantitative real-time PCR and cell counting kit-8 assay, respectively. Flow cytometry was conducted to detect apoptosis, followed by assessing the expression of related apoptosis factors. Dual-luciferase reporter assay was performed to validate the interaction between miR-877-5p and Forkhead cassette M1 (FOXM1). Our results showed that SP treatment significantly increased cell proliferation in gastric cancer. Moreover, the miR-877-5p expression was dose-dependently decreased by SP, whereas FOXM1 expression was markedly increased by SP in gastric cancer cells. miR-877-5p negatively regulated gastric cancer development via inhibiting cell proliferation and promoting apoptosis accompanied by increased cleaved caspase-3, cleaved caspase-9, and Bax protein levels and decreased Bcl-2 level. We confirmed that miR-877-5p could target FOXM1 and negatively regulate its expression. Furthermore, we demonstrated that SP could promote cell proliferation and inhibit apoptosis, while miR-877-5p overexpression reversed the effect of SP on cell proliferation and apoptosis. These results suggest that miR-877-5p overexpression can antagonize the promoting effect of SP on the development of gastric cancer, indicating that miR-877-5p may serve as a promising therapeutic target for gastric cancer.


Idelalisib and bendamustine combination is synergistic and increases DNA damage response in chronic lymphocytic leukemia cells.
Idelalisib is a targeted agent that potently inhibits PI3Kδ which is exclusively expressed in hematological cells. Bendamustine is a well-tolerated cytotoxic alkylating agent which has been extensively used for treatment of chronic lymphocytic leukemia (CLL). Both these agents are FDA-approved for CLL. To increase the potency of idelalisib and bendamustine, we tested their combination in primary CLL lymphocytes. While each compound alone produced a moderate response, combination at several concentrations resulted in synergistic cytotoxicity. Idelalisib enhanced the bendamustine-mediated DNA damage/repair response, indicated by the phosphorylation of ATM, Chk2, and p53. Each drug alone activated γH2AX but combination treatment further increased the expression of this DNA damage marker. Compared with the control, idelalisib treatment decreased global RNA synthesis, resulting in a decline of early-response and short-lived MCL1 transcripts. In concert, there was a decline in total Mcl-1 protein in CLL lymphocytes. Isogenic mouse embryonic fibroblasts lacking MCL1 had higher sensitivity to bendamustine alone or in combination compared to MCL1 proficient cells. Collectively, these data indicate that bendamustine and idelalisib combination therapy should be investigated for treating patients with CLL.


Experimental and clinical usefulness of crossmodal paradigms in psychiatry: an illustration from emotional processing in alcohol-dependence.
Crossmodal processing (i.e., the construction of a unified representation stemming from distinct sensorial modalities inputs) constitutes a crucial ability in humans' everyday life. It has been extensively explored at cognitive and cerebral levels during the last decade among healthy controls. Paradoxically however, and while difficulties to perform this integrative process have been suggested in a large range of psychopathological states (e.g., schizophrenia and autism), these crossmodal paradigms have been very rarely used in the exploration of psychiatric populations. The main aim of the present paper is thus to underline the experimental and clinical usefulness of exploring crossmodal processes in psychiatry. We will illustrate this proposal by means of the recent data obtained in the crossmodal exploration of emotional alterations in alcohol-dependence. Indeed, emotional decoding impairments might have a role in the development and maintenance of alcohol-dependence, and have been extensively investigated by means of experiments using separated visual or auditory stimulations. Besides these unimodal explorations, we have recently conducted several studies using audio-visual crossmodal paradigms, which has allowed us to improve the ecological validity of the unimodal experimental designs and to offer new insights on the emotional alterations among alcohol-dependent individuals. We will show how these preliminary results can be extended to develop a coherent and ambitious research program using crossmodal designs in various psychiatric populations and sensory modalities. We will finally end the paper by underlining the various potential clinical applications and the fundamental implications that can be raised by this emerging project.


Phase velocities and attenuations of shear, Lamb, and Rayleigh waves in plate-like tissues submerged in a fluid (L).
In the past several decades, the fields of ultrasound and magnetic resonance elastography have shown promising results in noninvasive estimates of mechanical properties of soft tissues. These techniques often rely on measuring shear wave velocity due to an external or internal source of force and relating the velocity to viscoelasticity of the tissue. The mathematical relationship between the measured velocity and material properties of the myocardial wall, arteries, and other organs with non-negligible boundary conditions is often complicated and computationally expensive. A simple relationship between the Lamb-Rayleigh dispersion and the shear wave dispersion is derived for both the velocity and attenuation. The relationship shows that the shear wave velocity is around 20% higher than the Lamb-Rayleigh velocity and that the shear wave attenuation is about 20% lower than the Lamb-Rayleigh attenuation. Results of numerical simulations in the frequency range 0-500 Hz are presented.


Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review.
Benign biliary strictures may be a consequence of surgical procedures, chronic pancreatitis or iatrogenic injuries to the ampulla. Stents are increasingly being used for this indication, however it is not completely clear which stent type should be preferred. A systematic review on stent placement for benign extrahepatic biliary strictures was performed after searching PubMed and EMBASE databases. Data were pooled and evaluated for technical success, clinical success and complications. In total, 47 studies (1116 patients) on outcome of stent placement were identified. No randomized controlled trials (RCTs), one non-randomized comparative studies and 46 case series were found. Technical success was 98,9% for uncovered self-expandable metal stents (uSEMS), 94,8% for single plastic stents and 94,0% for multiple plastic stents. Overall clinical success rate was highest for placement of multiple plastic stents (94,3%) followed by uSEMS (79,5%) and single plastic stents (59.6%). Complications occurred more frequently with uSEMS (39.5%) compared with single plastic stents (36.0%) and multiple plastic stents (20,3%). Based on clinical success and risk of complications, placement of multiple plastic stents is currently the best choice. The evolving role of cSEMS placement as a more patient friendly and cost effective treatment for benign biliary strictures needs further elucidation. There is a need for RCTs comparing different stent types for this indication.


Ethical and regulatory challenges in psychophysiology and neuroscience-based technology for determining behavior.
In the past three decades, there has been an explosion in research to understand the mechanisms of brain function. Recent advances in psychophysiology and neuroscience, while still limited, have sparked great interest in developing technologies that could peer into the brain and be used to identify or indicate certain behaviors. The polygraph (lie detector) represents an old technology used for discerning clues to the human brain; functional magnetic resonance imaging (fMRI) represents one of the newest efforts. The use of these technologies in intelligence and counterintelligence in the field without validation represents a major concern about its usefulness. Both research on this new technology and subsequent use on public raise ethical challenges. This article will address the overall ethical issues associated with these new technologies. The report identifies the ethical and cultural challenges in conducting research on these new tools, explores the possibility of using current U.S. regulatory requirements regarding drugs and devices as a model for regulating these new technologies, and suggests approaches for the future.


Filtered versus unfiltered technetium sulfur colloid in lymphatic mapping: a significant variable in a pig model.
Lymphatic mapping with sentinel node biopsy is becoming a standard diagnostic test for melanoma and is being extensively investigated for use with other soft tissue tumors. Both filtered and unfiltered technetium sulfur colloid (Tc 99) have been used for preoperative lymphoscintigraphy, as well as intraoperative lymphatic mapping, and it is not clear if one is preferable over the other. The purpose of this study was to compare these two preparations to determine whether the form of Tc 99 used affects the results of lymphatic mapping. Mock skin sites were placed on each extremity of 12 domestic pigs totaling 48 skin sites. Twenty-four of the lesions were injected with unfiltered Tc 99; the remaining 24 were injected with Tc 99 passed over a 0.2-microm filter. Both preparations of Tc 99 were mixed with 1 mL of isosulfan blue before injection. Sentinel node dissection was performed using a gamma probe, with counts recorded over a 10-second period and timed to begin 5 minutes after injection. Sentinel nodes were identified in all 48 lymph node basins draining the mock sites and characterized as hot (10x background), blue, or both. Significantly more sentinel nodes were found in the filtered (105 total, X = 4.4/basin), than in the unfiltered group (total 53, X = 2.2/basin, P <.0001). The filtered group had both a higher number of nodes that were hot (35 vs. 6) and more nodes that were hot and blue (69 vs. 43). In addition, hot secondary level lymph nodes (iliac and deep cervical) were found in 11 of 24 of the basins (46%) in the filtered group compared to 1 of 24 (4%) in the unfiltered group (P <.003). There was no significant difference in injection site or residual basin counts between the two groups, but in vivo counts over the sentinel node sites were significantly lower in the unfiltered group (X = 2670+/-1829 vs. X = 6027+/-4333; P = .003). Use of filtered Tc 99 results in more sentinel nodes (both hot/blue and hot non-blue) and a higher proportion of secondary lymph nodes. These findings indicate that the Tc 99 preparation used is a significant variable in the results of lymphatic mapping. It is critical that future clinical studies document which preparation of Tc 99 was used. Only large clinical trials will be able to determine whether the additional nodes found with filtered Tc 99 increase the sensitivity of the technique or merely increase the number of nodes that must be removed unnecessarily.


Neuron-astrocyte interactions in spinal cord dorsal horn in neuropathic pain development and docosahexaenoic acid therapy.
The analgesic activity of docosahexaenoic acid (DHA, 22:6 n-3) was studied using a chronic constriction injury (CCI) rat model. Animals were subcutaneously injected with DHA emulsion at a dose of 4.5mg/kg (125mМ/kg) daily during 2weeks after surgery. We characterized the dynamics of GFAP-positive astrocyte, substance P (SP) and nNOS-positive neurons activity in the spinal cord dorsal horn (SCDH) superficial lamina. We found that DHA treatment decrease the intensity and duration of neurogenic pain syndrome, results in earlier stabilization of weight distribution, prevents the cold allodynia and dystrophic changings in denervated limb tissue. DHA treatment reduced the reactive astrocyte number, decrease SP-immunopositive fibers and nNOS-positive neurons number in the SCDH in neuropathic pain.


Factors Affecting Hypertension in the Adult Population of the Marmara Region, Turkey: A Descriptive Field Study.
Hypertension is an increasingly prevalent global public health problem. Nutritional culture and lifestyle are among the factors related to hypertension. The aim of this study was to evaluate the prevalence and influential factors of hypertension in the adult population of the Marmara region, Turkey. The study was conducted in 10 provinces in the Marmara region between June 01, 2018, and November 30, 2018. Participants included 2353 patients over 18 years of age diagnosed with hypertension by any of the 30 family physicians working in the Family Health Centers in these provinces. After the participants provided written consent, a survey consisting of 25 questions was administered by their family physicians. SPSS 25.0 (IBM Corporation, Armonk, New York, United States) was used for all statistical analysis calculations. The patients included 1449 females (61.6%) and 904 males (38.4%). Among the respondents, 1555 (73.1%) had primary hypertension etiology and 572 (26.9%) had secondary etiology. While 1614 patients (68.6%) did not exercise at all, 739 patients (31.4%) reported exercising; 1026 patients (43.9%) did not restrict salt in their diet; and 1134 patients (48.2%) had a family history of hypertension. Since individual and environmental factors affect the etiology of hypertension, it is recommended that family physicians address these factors first as part of a holistic approach for hypertension prevention, diagnosis, treatment, and follow-up.


TV vs. YouTube: TV Advertisements Capture More Visual Attention, Create More Positive Emotions and Have a Stronger Impact on Implicit Long-Term Memory.
In an experiment, effects of commercials that are either shown within a TV program or embedded in YouTube videos were compared. These two media environments have not yet been compared empirically in terms of their advertising impact. A within-subjects design and a multi-method approach were used (N = 36). Eye tracking data show that more attention is allocated to advertisements that appear within a TV program compared to the YouTube-condition and the viewing experience elicited more positive emotions in the TV-condition. Two days after reception, no difference in recognition, likeability, and purchase intention occurred, but in terms of implicit long-term memory: In the TV condition, brands that were previously advertised but no longer remembered elicited stronger skin conductance change than brands for which no advertisements had previously been shown. In terms of advertising impact, TV seems to still be the better choice for advertisers. Presentation mode should be considered in future evaluation of advertisement potential.