Slippery to Sticky Transition of Hydrophobic Nanochannels.
Contrary to common intuition that hydrophobic surfaces trivially cause water to slip, we discover a slippery-to-sticky transition in tunable hydrophobic nanochannels. We demonstrate this remarkable phenomenon by bringing out hitherto unveiled interplay between ion inclusions in the water and the interfacial lattice configuration over molecular scales. The consequent alterations in frictional characteristics illustrate that so-called hydrophobic nanochannels can be switchable to manifest features that are otherwise typically associated with hydrophilicity, causing water to stick. Our proposition may bear immense consequences toward fluidically functionalizing a hydrophobic interface without necessitating elaborate surface treatment techniques, bringing in far-ranging implications in diverse applications ranging from nature to energy.


Cooperative Ge-N Bond activation in aluminium-functionalised aminogermanes and spontaneous imine elimination via an intermediate germyl cation.
Hydrometallation of iPr2 N-Ge(CMe3 )(C≡C-CMe3 )2 with H-M(CMe3 )2 (M=Al, Ga) affords alkenyl-alkynylgermanes in which the Lewis-acidic metal atoms are not coordinated by the amino N atoms but by the α-C atoms of the ethynyl groups. These interactions result in a lengthening of the Ge-C bonds by approximately 10 pm and a comparably strong deviation of the Ge-CC angle from linearity (154.3(1)°). This unusual behaviour may be caused by steric shielding of the N atoms. Coordination of the metal atoms by the amino groups is observed upon hydrometallation of Et2 N-Ge(C6 H5 )(C≡C-CMe3 )2 , bearing a smaller NR2 group. Strong M-N interactions lead to a lengthening of the Ge-N bonds by 10 to 15 pm and a strong deviation of the M atoms from the MC3 plane by 52 and 47 pm, for Al and Ga, respectively. Dual hydrometallation is achieved only with HAl(CMe3 )2 . In the product, there is a strong Al-N bond with converging Al-N and Ge-N distances (208 vs. 200 pm) and an interaction of the second Al atom to the phenyl group. Addition of chloride anions terminates the latter interaction while the activated Ge-N bond undergoes an unprecedented elimination of EtN=C(H)Me at room temperature, leading to a germane with a Ge-H bond. State-of-the-art DFT calculations reveal that the unique mechanism comprises the transfer of the amino group from Ge to Al to yield an intermediate germyl cation as a strong Lewis acid, which induces β-hydride elimination, with chloride binding being crucial for providing the thermodynamic driving force.


Prefrontal spatial working memory network predicts animal's decision making in a free choice saccade task.
While neurons in the lateral prefrontal cortex (PFC) encode spatial information during the performance of working memory tasks, they are also known to participate in subjective behavior such as spatial attention and action selection. In the present study, we analyzed the activity of primate PFC neurons during the performance of a free choice memory-guided saccade task in which the monkeys needed to choose a saccade direction by themselves. In trials when the receptive field location was subsequently chosen by the animal, PFC neurons with spatially selective visual response started to show greater activation before cue onset. This result suggests that the fluctuation of firing before cue presentation prematurely biased the representation of a certain spatial location and eventually encouraged the subsequent choice of that location. In addition, modulation of the activity by the animal's choice was observed only in neurons with high sustainability of activation and was also dependent on the spatial configuration of the visual cues. These findings were consistent with known characteristics of PFC neurons in information maintenance in spatial working memory function. These results suggest that precue fluctuation of spatial representation was shared and enhanced through the working memory network in the PFC and could finally influence the animal's free choice of saccade direction. The present study revealed that the PFC plays an important role in decision making in a free choice condition and that the dynamics of decision making are constrained by the network architecture embedded in this cortical area.


Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure.
PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature.


Quality of life and diagnostic imaging outcomes.
The US Preventive Services Task Force recently promulgated revised guidelines for screening mammography. Criticisms were related to the undervaluation of future lives saved and the overvaluation of negative impacts of mammography. Radiologists downplayed quality-of-life factors, potentially understating the value of all imaging procedures. The task force's recommendations for core needle biopsy, based on similar conceptual frameworks, were not met with equivalent responses. Full appreciation of the costs and benefits of screening provides the basis for making the best decisions for individuals and populations. This is undermined by the mixed messages that patients and physicians receive during clinical encounters and through other means. Quantitative approaches to medical care are valid on their own terms and when evaluated in the individual context. Insights from behavioral economics and political science inform discussion of population-based medical interventions. Preventing harm from medical interventions satisfies both the "primum non nocere" dictum and the loss aversion heuristic concordantly. The most effective medical care is provided when benefits are maximized and complications are minimized, especially when the harms occur immediately and the benefits are delayed. The importance of both quality of life and longevity in health care decision making require minimizing negative impacts of mammography when screening low-risk populations. Current practice differs significantly from the successful randomized trials, front-loading costs of false-positive examinations, and overtreatment. By decreasing false-positive mammographic results through adherence to ACR BI-RADS recommendations, radiologists can answer critics of early and frequent screening while still reducing cancer deaths.


Preparation and biological activity of some aminoacyl and peptidyl derivatives of 2'-amino-2'-deoxyuridine.
Several aminoacyl and peptidyl derivatives of 2'-amino-2'-deoxyuridine have been synthesized. 2'-Amino-2'-deoxyuridine (I) and 2'-N-glycyl-2'-amino-2'-deoxyuridine (IIIa) were condensed with N-Cbz blocked p-nitrophenyl esters of the appropriate amino acids to afford the protected aminoacyl and peptidyl nucleosides. Removal of the protecting groups gave the title compounds in good yields. The biological effects of these derivatives are discussed.


Small Extracellular Vesicles Derived From MSCs Have Immunomodulatory Effects to Enhance Delivery of ASO-210 for Psoriasis Treatment.
Mesenchymal stem cells (MSCs) have been increasingly used for treating autoimmune diseases due to their immune modulation functions, but inefficient homing to the target tissue and safety issues limits their wide application. Recently, increasing studies demonstrate small extracellular vesicles (sEVs) as key mediators of MSCs to exert their immunomodulatory effects. In this study, we found that sEVs derived from human umbilical cord MSCs stimulated by IFN-γ (IFNγ-sEVs) inhibited proliferation and activation of peripheral blood mononuclear cells and T cells in vitro. Furthermore, we confirmed that IFNγ-sEVs reduced psoriasis symptoms including thickness, erythema, and scales of skin lesions; exhausted Th17 cells, increased Th2 cells; and reduced enrichment of inflammatory cytokines such as IL-17A, IFN-γ, IL-6, and TNF-α in both spleen and skin lesions in vivo. Importantly, IFNγ-sEVs significantly improved the delivery efficiency and stability of ASO-210, the antisense oligonucleotides of miR-210 block the immune imbalance and subsequent psoriasis development. Our results reveal MSC-sEVs as promising cell-free therapeutic agents and ideal delivery vehicles of antisense oligonucleotides for psoriasis treatment.


Electron microscopy in the non-Hodgkin's lymphomata.
The component cells of peripheral lymphoid tissue have been divided into the lymphocyte and plasma cell lines, mononuclear phagocytic cells, dendritic "reticular cells", the reticular (supporting) cells and endothelial cells, and it is suggested that this system of cells should collectively be referred to as the lymphoreticular monoclear phagocyte system or LRMPS. Seventeen tumours of the LRMPS (excluding Hodgkin's disease) have been studied at ultrastructural level. Of these 17 non-Hodgkin lymphomata 5 were follicular lymphomata and 12 diffuse. It is concluded that electron microscopy plays a valuable role in the diagnosis of this group of tumours. Not only does it allow rejection of a diagnosis of lymphoma in certain anaplastic tumours, but it also enables a more precise identification of the cellular components of a lymphoma as well as indicating the degree of differentiation of the cell line involved. Additional advantages are the visualization of subcellular structures useful as markers, and by means of specialized immunoelectron microscopic techniques the identification of antigens and antibody formation within a given tumour. Two other results of this ultrastructural study are the indication that the dendritic cells of lymphoid follicles are derived from capillary endothelium, and the identification of certain anomalous formations derived from rough endoplasmic reticulum in the case of tumours showing plasmacytoid differentiation.


Cytotoxicity and genotoxicity of (+/-)-benzo[a]pyrene-trans-7,8-dihydrodiol in CYP1A1-expressing human fibroblasts quantitatively correlate with CYP1A1 expression level.
Cytochrome P450 1A1 (CYP1A1) activity is associated with increased susceptibility to lung cancer induced by polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BP). In non-hepatic human tissues, CYP1A1 is the principal enzyme responsible for the metabolic activation of the proximate BP mutagenic metabolite, (-)-benzo[a]pyrene-trans-7,8-dihydrodiol, to (+)-anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide, the ultimate BP mutagen. We have genetically engineered both DNA repair-deficient (xeroderma pigmentosum group A) and DNA repair-proficient human skin fibroblasts to express human CYP1A1 under control of the inducible mouse metallothionein-I promoter. CYP1A1 activity was induced by CdSO4 and monitored by following the O-deethylation of ethoxy fluorescein ethyl ester or of 7-ethoxyresorufin. Induced CYP1A1 activities were similar in both cell lines and were dependent on CdSO4 concentration and induction time. Maximal CYP1A1 activities were obtained in 4-6 h with 5-7 microM CdSO4. BPD-induced cytotoxicity and hypoxanthine phosphoribosyl transferase mutagenicity were both quantitatively correlated with the level of CYP1A1 activity and were greater in DNA repair-deficient cells than in DNA repair-proficient cells. The results suggest that modestly induced CYP1A1 activity is a risk factor in polycyclic aromatic hydrocarbon-induced carcinogenesis.


Comparative pharmacokinetics of dicloxacillin and ampicillin between individual and combined doses.
Pharmacokinetics of dicloxacillin and ampicillin dosed individually and in combination were investigated by means of moment analyses of urinary excretions of intact forms and metabolic products of parent penicillins. Comparison of excretion profiles between individual and combined doses to human subjects indicated that the transformation of ampicillin to penicilloic acid and subsequent conversion to secondary metabolite are suppressed by the simultaneous dose of dicloxacillin, while the total excretion ratio to dose and the mean residence times in the body remain almost unchanged. The excretion profiles of dicloxacillin and metabolites are not significantly affected by the combined dose.


GREMLIN 2 Mutations and Dental Anomalies.
Isolated or nonsyndromic tooth agenesis or hypodontia is the most common human malformation. It has been associated with mutations in MSX1, PAX9, EDA, AXIN2, EDAR, EDARADD, and WNT10A. GREMLIN 2 (GREM2) is a strong bone morphogenetic protein (BMP) antagonist that is known to regulate BMPs in embryogenesis and tissue development. Bmp4 has been shown to have a role in tooth development. Grem2(-/-) mice have small, malformed maxillary and mandibular incisors, indicating that Grem2 has important roles in normal tooth development. Here, we demonstrate for the first time that GREM2 mutations are associated with human malformations, which include isolated tooth agenesis, microdontia, short tooth roots, taurodontism, sparse and slow-growing hair, and dry and itchy skin. We sequenced WNT10A, WNT10B, MSX1, EDA, EDAR, EDARADD, AXIN2, and PAX9 in all 7 patients to rule out the effects of other ectodermal dysplasias and other tooth-related genes and did not find mutations in any of them. GREM2 mutations exhibit variable expressivity even within the same families. The inheritance is autosomal dominant with incomplete penetrance. The expression of Grem2 during the early development of mouse teeth and hair follicles and the evaluation of the likely effects of the mutations on the protein structure substantiate these new findings.


Use of schizophrenia as a metaphor in US newspapers.
Research has identified misleading and stigmatizing popular beliefs about schizophrenia, but little is known about media images corresponding to these beliefs. Building on Susan Sontag's exploration of cancer in the 1978 book Illness as Metaphor, the authors hypothesize that "schizophrenia" is now more commonly misused. A total of 1740 newspaper articles from 1996 or 1997 that mentioned schizophrenia or cancer were randomly selected and then coded for contextual and metaphorical use. Only 1 percent of articles that mentioned cancer used that illness in a metaphorical way, compared with 28 percent of the articles that mentioned schizophrenia. Results differed by newspaper but not by region. The authors suggest that these inaccurate metaphors in the media contribute to the ongoing stigma and misunderstandings of psychotic illnesses.


Plexin-B1 Mutation Drives Metastasis in Prostate Cancer Mouse Models.
Metastatic prostate cancer is essentially incurable and is a leading cause of cancer-related morbidity and mortality in men, yet the underlying molecular mechanisms are poorly understood. Plexins are transmembrane receptors for semaphorins with divergent roles in many forms of cancer. We show here that prostate epithelial cell-specific expression of a mutant form of Plexin-B1 (P1597L) which was identified in metastatic deposits in patients with prostate cancer, significantly increases metastasis, in particular metastasis to distant sites, in two transgenic mouse models of prostate cancer (PbCre+Ptenfl /flKrasG12V and PbCre+Ptenfl /flp53fl/ fl ). In contrast, prostate epithelial cell-specific expression of wild-type (WT) Plexin-B1 in PbCre+Ptenfl /flKrasG12V mice significantly decreases metastasis, showing that a single clinically relevant Pro1597Leu amino-acid change converts Plexin-B1 from a metastasis-suppressor to a metastasis-promoter. Furthermore, PLXNB1P1597L significantly increased invasion of tumor cells into the prostate stroma, while PLXNB1WT reduced invasion, suggesting that Plexin-B1 has a role in the initial stages of metastasis. Deletion of RhoA/C or PDZRhoGEF in Ptenfl /flKrasG12VPLXNB1P1597L mice suppressed metastasis, implicating the Rho/ROCK pathway in this phenotypic switch. Germline deletion of Plexin-B1, to model anti-Plexin-B1 therapy, significantly decreased invasion and metastasis in both models. Our results demonstrate that Plexin-B1 plays a complex yet significant role in metastasis in mouse models of prostate cancer and is a potential therapeutic target to block the lethal spread of the disease. Few therapeutic targets have been identified specifically for preventing locally invasive/oligometastatic prostate cancer from becoming more widely disseminated. Our findings suggest Plexin-B1 signaling, particularly from the clinically relevant P1597L mutant, is such a target.


Glycoprotein Ibalpha forms disulfide bonds with 2 glycoprotein Ibbeta subunits in the resting platelet.
It is widely accepted that glycoprotein (GP) Ib contains one Ibalpha and one Ibbeta subunit that are connected by a disulfide bond. It is unclear which Cys residue in Ibalpha, C484 or C485, forms the disulfide bond with Ibbeta. Using mutagenesis studies in transfected Chinese hamster ovary (CHO) cells, we found that both C484 and C485 formed a disulfide bond with C122 in Ibbeta. In the context of isolated peptides containing the Ibalpha or Ibbeta transmembrane domain and nearby Cys residue, C484 and C485 in the Ibalpha peptide were both capable of forming a disulfide bond with the Ibbeta peptide. Furthermore, coimmunoprecipitation of epitope-tagged subunits showed that at least 2 Ibbeta subunits but only 1 Ibalpha and 1 IX subunit were present in the GP Ib-IX complex. Finally, the size difference between GP Ib from transfected CHO cells and human platelets was attributed to a combination of sequence polymorphism and glycosylation difference in Ibalpha, not the number of Ibbeta subunits therein. Overall, these results demonstrate that Ibalpha is covalently connected to 2 Ibbeta subunits in the resting platelet, necessitating revision of the subunit stoichiometry of the GP Ib-IX-V complex. The alphabeta2 composition in GP Ib may provide the basis for possible disulfide rearrangement in the receptor complex.


An experimental study of embolic effect according to infusion rate and concentration of suspension in transarterial particulate embolization.
The authors evaluate the embolic effect according to infusion rate and concentration of particulate suspension, focusing on arterial occlusion level. The renal arteries of 14 rabbits were embolized with 150 to 250 microns polyvinyl alcohol (PVA) particles, divided into four groups according to two different infusion rates (1 mg/second and 0.1 mg/second) and two different concentrations of suspension (10 mg/mL and 2.5 mg/mL). Arteriograms obtained immediately and a week after embolization were assessed for occlusion level. For the nephrograms obtained a week after embolization, the opacifying areas were graded from 0 to 4. Median coronal sections of each kidney specimen were investigated for the presence of peripheral infarct grossly and for the presence of PVA particles in the small artery microscopically. Arteriograms showed various occlusion levels. Using a 0 to 4 grading system, the opacifying area of the nephrogram obtained 1 week after embolization was noted to be smaller in the low infusion rate group (P < 0.05). In gross and microscopic pathologic examination, the number of cases with peripheral infarct or PVA particles in the small artery (< 300 microns) was greater in the group with the low infusion rate and low concentration (P < 0.05). In transarterial particulate embolization, slower infusion of more diluted suspension provides for a more distal arterial occlusion.


[Antiviral activity of a hammerhead ribozyme against HBV in HepG2.2.15 cells].
The carboxy terminal arginine rich domain of core protein is highly conserved among HBV subtypes, and plays important roles in the packaging of pregenomic RNA and viral replication. Therefore, the 3' highly conserved region of HBV C gene is an attractive target for antiviral therapy mediated by ribozymes. A hammerhead ribozyme RzC, targeting the above site, was designed; meanwhile, as controls, the disabled form of RzC, dRzC, was also designed. In order to investigate its antiviral effects in cultured cells, in vitro-transcribed ribozymeRzC, dRzC and ribozyme expression vectors pCRzC, pCdRzC were delivered, respectively, into HepG2.2.15 cells ( clonal cells derived from HepG2 cells that contain integrated HBV ayw DNA). The preliminary results demonstrated that in vitro-transcribed ribozyme RzC had weak inhibition on HBV replication, possibly due to its quick degradation by RNases in cells, while the endogenously expressed ribozyme RzC showed significant inhibitory effect on HBV replication. In conclusion, the results suggested the possibility of the hammerhead ribozyme RzC to be used for the gene therapy of HBV infection.


[An algorithm for synthesis of small-size autonomous devices for detection of medico-biological parameters].
Problems of synthesis of devices for detection of medico-biological parameters are considered. A classification of the devices and their functional units is proposed. An algorithm for synthesis of detectors of medico-biological parameters on the basis of multiple-use functional units is suggested. The algorithm is based on analysis of functional unit modifications providing optimization of the device characteristics.


Nuchal-type fibroma of the ankle: a case report.
Nuchal-type fibroma is rare benign fibrous tumor that has the potential to recur. It is typically located in the subcutaneous tissues of the posterior aspect of the neck, although it can affect other anatomical sites. Extranuchal involvement occurs most commonly in the back, shoulder, and face, as well as other sites specified in single case reports. In this report, we describe the case of a patient presenting with a nuchal-type fibroma arising in the ankle. The lesion infiltrated the superior extensor retinaculum. Marginal resection was performed, and there was no evidence of recurrence after 12 months of follow-up. To our knowledge, this is the first report of a nuchal-type fibroma localized to the ankle.


Multiple functions of the E3 ubiquitin ligase CHIP in immunity.
The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner. In addition, through tight regulation of the protein level of its substrates, CHIP plays important roles in many physiological and pathological conditions, including cancers, neurological disorders, cardiac diseases, bone metabolism, immunity, and so on. Nonetheless, the precise mechanisms underlying the regulation of the immune system by CHIP are still poorly understood despite accumulating developments in our understanding of the regulatory roles of CHIP in both innate and adaptive immune responses. In this review, we also aim to provide a view of CHIP-mediated regulation of immune responses and the signaling pathways involved in the model described. Finally, we discuss the roles of CHIP in immune-related diseases.


Type effect of inhibitory KT tape on measured vs. perceived maximal grip strength.
This study examined the effects of KT tape (KT) applied in an inhibitory manner on muscle activity, measured maximal grip strength, and perceived maximal grip strength in regular KT-users and non-users. This study was a single-blinded crossover study with sixty participants including 27 kT-users and 33 non-users. Participants underwent maximal grip strength tests with and without inhibitory KT applied across the wrist extensors. Muscle activity and maximal grip strength were measured, while perceived maximal grip strength was rated using a visual analogue scale. No significant interaction effect was found between taping conditions and participant KT-experience for muscle activity (F = 0.825, p = 0.367), measured grip strength (F = 1.018, p = 0.317) or perceived grip strength (F = 0.122, p = 0.728). No significant differences were observed in the EMG activity between taping conditions for either KT-users (p = 0.367) or non-users (p = 0.215). A similar trend was found in the measured grip strength (KT-users: p = 0.317; non-users: p = 0.294) and perceived grip strength (KT-users: p = 0.728; non-users: p = 0.063). KT applied in an inhibitory manner does not impede EMG activity, measured maximal grip strength, or perceived maximal grip strength in adults, regardless of their preconceived notions of KT.


Cross-scale predictive modeling of CHO cell culture growth and metabolites using Raman spectroscopy and multivariate analysis.
Multi-component, multi-scale Raman spectroscopy modeling results from a monoclonal antibody producing CHO cell culture process including data from two development scales (3 L, 200 L) and a clinical manufacturing scale environment (2,000 L) are presented. Multivariate analysis principles are a critical component to partial least squares (PLS) modeling but can quickly turn into an overly iterative process, thus a simplified protocol is proposed for addressing necessary steps including spectral preprocessing, spectral region selection, and outlier removal to create models exclusively from cell culture process data without the inclusion of spectral data from chemically defined nutrient solutions or targeted component spiking studies. An array of single-scale and combination-scale modeling iterations were generated to evaluate technology capabilities and model scalability. Analysis of prediction errors across models suggests that glucose, lactate, and osmolality are well modeled. Model strength was confirmed via predictive validation and by examining performance similarity across single-scale and combination-scale models. Additionally, accurate predictive models were attained in most cases for viable cell density and total cell density; however, these components exhibited some scale-dependencies that hindered model quality in cross-scale predictions where only development data was used in calibration. Glutamate and ammonium models were also able to achieve accurate predictions in most cases. However, there are differences in the absolute concentration ranges of these components across the datasets of individual bioreactor scales. Thus, glutamate and ammonium PLS models were forced to extrapolate in cases where models were derived from small scale data only but used in cross-scale applications predicting against manufacturing scale batches.


Central involvement of kinin B1 and B2 receptors in the febrile response induced by endotoxin in rats.
1. The effect of central injection of selective kinin B1 and B2 receptor antagonists on the febrile response induced by endotoxin (E. coli lipopolysaccharide, LPS) in rats was investigated. 2. Intracerebroventricular (i.c.v.) injection of a selective B2 receptor antagonist (Hoe-140, 8 nmol) reduced the early (0-2 h), but increased the late phase (4-6 h) of the febrile response induced by intravenous (i.v.) injection of LPS (0.5 microgram kg-1). 3. Co-administration of Hoe-140 (8 nmol, i.c.v.) with LPS (0.5 microgram kg-1, i.v.), followed 2.5 h later by the i.c.v. injection of a selective B1 receptor antagonist [des-Arg9-Leu8]-bradykinin (BK, 8 nmol), significantly reduced the febrile response induced by LPS throughout the whole experimental period. 4. Intravenous injection of Hoe-140 (1 mg kg-1) significantly reduced the febrile response induced by LPS (0.5 microgram kg-1, i.p.). 5. Pretreatment (24 h) with LPS (0.5 microgram kg-1, i.v.) reduced the febrile response induced by BK or [Tyr8]-BK (both, 5 nmol, i.c.v.), but markedly increased the febrile response induced by [des-Arg9]-BK (5 nmol, i.c.v.). The response induced by [des-Arg9]-BK in LPS-pretreated rats was significantly inhibited by co-injection of [des-Arg9-Leu8]-BK (15 nmol, i.c.v.). 6. The results suggest that kinins are involved in the induction of LPS-induced fever and that central B2 and B1 receptors are activated during the initial and late phase of this response, respectively. The results also suggest that downregulation and/or desensitization of B2 receptors and induction and/or upregulation of B1 receptors in LPS-pretreated animals may have a significant pathophysiological role in the induction and maintenance of fever. These observations may be specifically important in the case of chronic inflammatory conditions, because the BK metabolite [des-Arg9]-BK, so far considered an inactive metabolite, acquires an active and relevant role with the progressive expression of B1 receptors that occurs in such states.


Standardization of In Vitro Studies for Plasmonic Photothermal therapy.
Lack of standardization is a systematic problem that impacts nanomedicine by challenging data comparison from different studies. Translation from preclinical to clinical stages indeed requires reproducible data that can be easily accessed and compared. In this work, we propose a series of experimental standards for in vitro plasmonic photothermal therapy (PPTT). This best practice guide covers the five main aspects of PPTT studies in vitro: nanomaterials, biological samples, pre-, during, and postirradiation characterization. We are confident that such standardization of experimental protocols and reported data will benefit the development of PPTT as a transversal therapy.


Cross-Domain Traffic Scene Understanding by Integrating Deep Learning and Topic Model.
Understanding cross-domain traffic scenarios from multicamera surveillance network is important for environmental perception. Most of existing methods select the source domain which is most similar to the target domain by comparing entire domains for cross-domain similarity and then transferring the motion model learned in the source domain to the target domain. The cross-domain similarity between overall different scenarios with similar local layouts is usually not utilized to improve any automatic surveillance tasks. However, these local commonalities, which may be shared across multiple traffic scenarios, can be transferred across scenarios as prior knowledge. To address these issues, we present a novel framework for cross-domain traffic scene understanding by integrating deep learning and topic model. This framework leverages the labeled samples with activity attribute labels from the source domain to annotate the target domain, where each label represents the local activity of some objects in the scene. When labeling the activity attributes of the target domain, there is no need to select the source domain, which avoids the phenomenon of performance degradation or even negative transfer due to wrong source domain selection. The effectiveness of the proposed framework is verified by extensive experiments carried out using public road traffic data.


The interplay of protein kinase A and perilipin 5 regulates cardiac lipolysis.
Defective lipolysis in mice lacking adipose triglyceride lipase provokes severe cardiac steatosis and heart dysfunction, markedly shortening life span. Similarly, cardiac muscle (CM)-specific Plin5 overexpression (CM-Plin5) leads to severe triglyceride (TG) accumulation in cardiomyocytes via impairing TG breakdown. Interestingly, cardiac steatosis due to overexpression of Plin5 is compatible with normal heart function and life span indicating a more moderate impact of Plin5 overexpression on cardiac lipolysis and energy metabolism. We hypothesized that cardiac Plin5 overexpression does not constantly impair cardiac lipolysis. In line with this assumption, TG levels decreased in CM of fasted compared with nonfasted CM-Plin5 mice indicating that fasting may lead to a diminished barrier function of Plin5. Recent studies demonstrated that Plin5 is phosphorylated, and activation of adenylyl cyclase leads to phosphorylation of Plin5, suggesting that Plin5 is a substrate for PKA. Furthermore, any significance of Plin5 phosphorylation by PKA in the regulation of TG mobilization from lipid droplets (LDs) is unknown. Here, we show that the lipolytic barrier of Plin5-enriched LDs, either prepared from cardiac tissue of CM-Plin5 mice or Plin5-transfected cells, is abrogated by incubation with PKA. Notably, PKA-induced lipolysis of LDs enriched with Plin5 carrying a single mutation at serine 155 (PlinS155A) of the putative PKA phosphorylation site was substantially impaired revealing a critical role for PKA in Plin5-regulated lipolysis. The strong increase in protein levels of phosphorylated PKA in CM of Plin5 transgenic mice may partially restore fatty acid release from Plin5-enriched LDs, rendering these hearts compatible with normal heart function despite massive steatosis.


8-Propyldithieno[3,2-b:2',3'-e]pyridine-3,5-diamine (DITIPIRAM) Derivatives as Neutral Receptors Tailored for Binding of Carboxylates.
The DITIPIRAM (8-propyldithieno[3,2-b:2',3'-e]pyridine-3,5-diamine)-based receptors 11 and 12 were readily synthesized, and their anion-binding properties were studied both in solution and in the solid-state. 1H NMR titrations revealed that receptor 12 equipped with two phenyl-urea groups preferentially binds carboxylates, even in the highly competitive DMSO-d6/CD3OH solvent mixture. X-ray analysis showed that receptor 12 exhibited great complementarity for benzoate, which is cooperatively bound by the means of four highly directional hydrogen bonds from the two urea groups. Comparison with the most effective acyclic receptors based on a structurally related rigid carbazole platform demonstrates that the DITIPIRAM motif provides a better suited geometry in the binding pocket, and consequently stronger anion binding.


Centers of excellence: a new dimension in surgical education.
Surgical education has always been challenging and is being made more difficult with the changes in the surgical environment. In the past decade, the number of patients available for educational purposes has decreased because of the development of technology that has significantly reduced their time of stay in the hospital and has also moved many surgical procedures to ambulatory services. Technologic advances also create the demand for more specialized training. The increased number of undergraduate, postgraduate students, and clinical fellows has also affected the educational mandate of the academic hospitals. Alternative ways to teach medicine, and especially surgery, are becoming inevitable. One such method is to teach students outside the operating room in a simulated environment. This article reports on the developments of surgical education centers and provides guidance for those who might wish to develop such educational facilities. For further information, visit www.cesei.org.


Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells.
In a previous study, we demonstrated that calponin h1 suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16-F10 melanoma (F10) cells was more extensive in calponin h1-deficient (CN(-/-)) mice with fragility of mesothelial (MS) cells than in their calponin h1-wild (CN(+/+)) counterparts. In our study, we assessed the therapeutic effect of calponin h1 on peritoneal dissemination. F10 cells were overlaid on the cultured CN(+/+) or CN(-/-) MS cells and the effect of calponin h1 on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin h1 gene (AdGFP-CN) inserted was constructed and was applied to CN(-/-) MS cells or CN(-/-) mouse peritoneum to investigate its suppressive effect on the peritoneal dissemination caused by F10 cells. Greater retraction and invasion of F10 cells were observed in CN(-/-) MS than in CN(+/+) cells in vitro, while down-regulation of calponin h1 was observed in CN(+/+) MS cells prior to the invasion of F10 cells. Infecting CN(-/-) MS cells with AdGFP-CN prevented their retraction and the invasion of F10 cells. Peritoneal dissemination was prominently suppressed in AdGFP-CN-infected CN(-/-) mice, and the survival of those mice was significantly prolonged. Thus, calponin h1 functioned to protect host MS cells from the invasion of F10 cells.


The effect of furosemide on sodium and potassium concentrations in guinea-pig perilymph.
To observe the effects of furosemide on electrolyte concentrations in inner-ear fluids, experiments were performed on 286 normal guinea-pigs. Intravenous injection of furosemide (15 mg/kg) induced increases of Na concentration in scala tympani perilymph, scala vestibuli perilymph, and cerebrospinal fluid (CSF). K concentrations in both perilymphs and CSF were also increased by furosemide. The increased Na concentrations are thought to be due to the dehydration of body fluids induced by the diuretic action of furosemide. The increase of K concentrations in perilymphs could be attributable to either a characteristic action of furosemide on the electrolyte transport in the inner ear or a secondary change caused by a rise of K concentration in the endolymph.


Attitudes of Mexican anesthesiologists to indicate preoperative fasting periods: A cross-sectional survey.
BACKGROUND: In Mexico, guidelines for fasting periods, or any audits on this topic are unavailable, and therefore the attitudes of anesthesiologists for recommending preoperative fasting periods are unknown. MATERIAL AND METHODS: The study was a cross-sectional survey of anesthesiologists subscribed to the Annual Updated Course, organized by the Sociedad Mexicana de Anestesiologia in 2000. The response rate was 31.4%. RESULTS: Most respondents were general anesthesiologists, with 5 or more years experience in a clinical post, were working in both public and private hospitals, and were performing anesthetic procedures on both pediatric and adult patients and in both ambulatory and hospitalized patients. Approximately 23% of the respondents considered natural fruit juices to be clear liquids. For a pediatric patient ingesting breast milk 1 h before undergoing a surgical procedure, 45% thought that surgery should be delayed for 3h, followed by those delaying the surgical procedure for 6 to 8 h. Our results show that more than 50% of the anesthesiologists had better defined attitudes for fasting milk and clear liquids in patients of 6 month or under than for older children and adults. However, due to the poor definition or pre-operative fasting, using clear liquids, in all other patient groups, several patients are allowed to go without oral clear liquids administration for prolonged periods. CONCLUSION: Preoperative fasting periods recommended by Mexican anesthesiologists differ from international guidelines.


Exercise equipment and diabetes.
Regular exercise is one of the most powerful treatments for the prevention and treatment of insulin resistance and type 2 diabetes mellitus. Exercise is also beneficial for those living with type 1 diabetes although challenges exist with its prescription as it can promote both hyperglycaemia and hypoglycaemia and motivating patients is always a challenge. Nonetheless, promoting regular exercise should be the cornerstone of all healthcare professionals working with these patients. In this year's review on exercise and exercise equipment, we highlight 10 publications that focus on topics ranging from exercise adherence to fuel metabolism. We also highlight some new innovative tools that facilitate exercise participation and evaluation.


Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria.
Mitochondria isolated from normal rat liver and AS-30D hepatoma were concurrently evaluated with regard to their bioenergetic and metabolic properties. AS-30D mitochondria oxidized many NAD-linked respiratory substrates at rates 1.5-4 times faster than those from liver, a fact which contributes to their diminished membrane depolarization on conversion from state 4 to state 3 respiration. AS-30D mitochondria exhibited no signs of a "truncated" Krebs cycle, nor did they oxidize malate preferentially based upon its origin in the cytosol or the mitochondrial matrix. In addition, beta-oxidation in AS-30D mitochondria was not sufficient to suppress respiratory CO2 production and induce pyruvate carboxylation to the extent observed in liver. Finally, AS-30D mitochondria were able to oxidize externally generated NADH in a reconstituted system, but in a manner independent of the transmembrane electrical potential (delta psi), suggesting that the malate-aspartate shuttle is not operable in vivo. This fact may necessitate the adaptations tumor cells make to reoxidize cytosolic NADH through glycolysis even in the presence of adequate oxygen.


Comparison of visual shade matching and photographic shade analysis.
To compare the performance of a standardized photographic shade analysis (PSA) and visual shade matching (VSM) using two color difference formulas. Fifty observers (35 undergraduate and 15 graduate students) evaluated the color of two upper left central incisors (LT-light tooth, and DT-dark tooth). VSM was performed using the VITA 3D Master (3D) shade guide in a controlled clinical environment. For PSA, a cross-polarized filter and a gray card (Whibal) were used to standardize the photographs taken (target teeth and shade tabs from 3D). From the pictures obtained, the CIELAB coordinates, and color differences ( Δ E ab * and ΔE00 ) were obtained. The shade tabs selected by two experienced researchers were conducted as part of the pilot study, and finally used as a standard for the analysis. Data were analyzed using descriptive statistics and the chi-square test (p ≤ 0.05). Shade tabs selections of VSM and PSA agreed only for LT. The best "Match" selected by the researchers agreed with data from PSA using ΔE00 . PSA using ΔE00 showed higher total percentages of "Match" and higher percentage of agreement among observers. A relationship was found for LT performing the PSA (p < 0.05). The performance of the PSA was better than the VSM, but only when the CIEDE2000 color difference formula was used. Therefore, the color difference formulas influenced on the performance of PSA. Finally, the PSA improved the precision of the VSM. To use a standardized PSA to improve the VSM and shade communication in clinical esthetic dentistry.


Transesophageal echocardiography in critically ill patients.
To evaluate the safety and utility of transesophageal echocardiography performed by intensive care physicians in critically ill patients. Retrospective chart review. A 24-bed multidisciplinary adult intensive care unit in a 692-bed tertiary referral teaching hospital. Two hundred fifty-five intensive care patients. We studied 255 consecutive intensive care patients who underwent transesophageal echocardiography between January 1996 and January 2000. Three hundred eight transesophageal echocardiography studies were successfully performed; the probe could not be passed in one patient with a cervical fracture. The indications included unexplained hypotension (40%), known or suspected endocarditis (27%), assessment of ventricular function (15%), pulmonary edema (5%), source of embolus (4%), assessment of aorta (4%), and other (5%). In 67% of hypotensive patients, transesophageal echocardiography revealed the cause of hemodynamic instability, leading to a management change and improvement in blood pressure in 31%. This included surgery in 22% without the need for additional tests. Overall, transesophageal echocardiography findings led to a significant change in management in 32% of all studies performed. One patient receiving continuous positive airways pressure suffered pulmonary aspiration during tracheal intubation before transesophageal echocardiography, two patients had hypotension associated with sedative medication, and there was one case of oropharyngeal bleeding after probe insertion. Transesophageal echocardiography when performed by intensive care physicians is a safe procedure and provides useful information for the evaluation and management of critically ill patients.


Analysis of mitochondrial organization and function in the Drosophila blastoderm embryo.
Mitochondria are inherited maternally as globular and immature organelles in metazoan embryos. We have used the Drosophila blastoderm embryo to characterize their morphology, distribution and functions in embryogenesis. We find that mitochondria are relatively small, dispersed and distinctly distributed along the apico-basal axis in proximity to microtubules by motor protein transport. Live imaging, photobleaching and photoactivation analyses of mitochondrially targeted GFP show that they are mobile in the apico-basal axis along microtubules and are immobile in the lateral plane thereby associating with one syncytial cell. Photoactivated mitochondria distribute equally to daughter cells across the division cycles. ATP depletion by pharmacological and genetic inhibition of the mitochondrial electron transport chain (ETC) activates AMPK and decreases syncytial metaphase furrow extension. In summary, we show that small and dispersed mitochondria of the Drosophila blastoderm embryo localize by microtubule transport and provide ATP locally for the fast syncytial division cycles. Our study opens the possibility of use of Drosophila embryogenesis as a model system to study the impact of maternal mutations in mitochondrial morphology and metabolism on embryo patterning and differentiation.


Corneal endothelial cells are protected from apoptosis by gene therapy.
Corneal grafting is the most prevalent form of transplantation. Corneal endothelial cells (ECs), which form a monolayer of the cornea with minimal proliferative potential, are pivotal for maintenance of corneal clarity. Loss of EC viability and apoptosis leads to graft failure posttransplantation and reduces the quality of donor corneas in storage, such that up to 30% do not meet selection criteria and must be discarded. The current study investigates antiapoptotic effects of transduced mammalian Bcl-x(L) and baculoviral p35 on human ECs. Multiple apoptotic cell features are observed while inducing apoptosis either via the extrinsic (death receptor) or intrinsic (mitochondrial) apoptotic pathway. Human ECs were studied under three experimental conditions: (1) as an immortalized cell line, (2) as primary cells, and (3) in an intact cornea. Interestingly, in primary EC suspensions, Bcl-x(L) was protective against apoptosis mediated via both pathways. However, p35 was significantly more protective against apoptosis mediated via the intrinsic pathway compared with Bcl-x(L). Our results provide critical insight into the role of apoptotic pathways in the maintenance of EC viability and the efficacy with which these protective proteins exert their effect. These observations could form the basis for future applications of antiapoptotic gene therapy to corneal preservation aiming to reduce both graft failure after transplantation as well as donor corneal damage during storage.


Targeting silymarin for improved hepatoprotective activity through chitosan nanoparticles.
Silymarin is one of the best known hepatoprotective drugs, which is obtained from the seeds of Silybum marianum L., Family: Asteraceae or Compositae. The plant has traditionally been used for centuries as a natural remedy for liver and biliary tract diseases. The aim of the present investigation was to enhance the hepatoprotective activity of silymarin by incorporating it in chitosan (Ch) nanoparticles (NPs) for passive targeted delivery, thereby prolonging its retention time. Silymarin loaded NPs were prepared by ionic gelation technique, which were then optimized using a central composite design in order to minimize the particle size and maximize the drug entrapment efficiency. The optimized formulation was evaluated for in vitro drug release study and in vitro study on Swiss Albino mice using carbon tetrachloride (CCL4) induced hepatotoxicity model. In vitro dissolution studies illustrated sustained, zero order drug release from optimized formulation; also its therapeutic potential was amplified during in vitro studies on Swiss Albino mice using CCL4 induced hepatotoxicity model. The results suggested that NPs of silymarin could successfully enhance its hepatoprotective effect by passive targeting and sustained release.


Concurrent validity of three self-report measures of assertiveness.
The relative validity of three self-report measures of assertiveness was assessed by correlating the scored obtained by 88 student nurses with peer and faculty ratings of assertiveness. Self-reported assertiveness failed to predict frequency of class participation within a subsample of 48 students. Type of instructional setting, however, did exert a significant effect on class participation.


Communication between general practitioners and patients dying at home.
Semi-structured interviews were carried out with four general practitioners and some of their terminally ill patients in order to investigate how doctors solve the problem of communication with these patients about the outcome of the illness. Three of the doctors preferred not to give explicit information, or to talk about the outcome, even when they knew that the patient realised that he or she was dying. Within this constraint they developed different ways of coping with the problem of how to talk to the patient. We interpret this behaviour as an attempt to remain within the framework of rules and expectations provided by the traditional roles of doctor and patient, a framework that would be threatened by the doctor's acknowledgement of helplessness. The fourth doctor did tell his patients, and treated the problem as one of counselling patients to help them cope with their predicament. His role of healer was thus extended to include terminally ill patients.


Brazilian Portuguese Hearing in Noise Test (HINT): different interpretation criteria for individuals' responses.
The ability to recognize the sounds of speech enables an efficient communication. This ability must always be considered when communication disorders are evaluated. In this study, sentences of the Hearing in Noise Test (HINT), originally developed in English and adapted to Brazilian Portuguese, were used to evaluate speech recognition in silence and in the presence of noise. Although this test can be an important clinical tool, it is noticed that it has not been used in audiological clinical practice in Brazil. One possible reason is the lack of standardization of some aspects of the test, including the methods adopted to analyze the patient's answers. The aim of this study was to analyze different judgment criteria of individuals' answers during sentence recognition thresholds measurement using the HINT in Brazilian Portuguese. The study was conducted with 30 young adults (three groups of 10 people), between 18 and 25 years old, of both genders, with normal hearing. HINT sentences were adapted to Brazilian Portuguese and speech recognition thresholds were determined in the presence of noise by using three judgment criteria published in Brazilian literature. A single variation analysis was performed to compare the average threshold between the three groups. The maximum error probability to reject the null hypothesis was 5%. The mean and standard deviations of thresholds, respectively, were: 59.90 ± 1.43 dB SPL; 59.60 ± 0.53 dB SPL and 59.95 ± 0.6 dB SPL. There was no statistically significant difference between the means (F = 0.398; p> 0.05). Regardless the judging criteria used, results obtained in all groups were equivalent.


Differential resistance of GaN-based laser diodes with and without polarization effect.
In this paper, we used numerical calculation and simulation to investigate the differential resistance of GaN-based laser diodes (LDs) with and without polarization effect. We confirmed the existence of a kink at the vicinity of threshold current in the differential resistance curve of GaN-based LDs and found that the kink polarity can be reversed dependent on the polarization effect. The serial parasitic diodes should be included in the theoretical analysis of the equivalent circuit of the LD devices. We determined that the superposition effects of the n-side, active, and p-side regions of the LDs caused the kink and its polarity. We also found that the differential resistance before and after the threshold was dominated by the p-side region and its gradual reduction is related to an electron overflow into p-side. Finally, we studied the effects of cavity facet reflectivity on the kink.


GIST: particular aspects related to cell cultures, xenografts, and cytogenetics.
In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged from historical anonymity to become a model of kinase-targeted therapies. Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic value. In this regard, the in vitro and in vivo models have provided valuable tools for understanding the molecular pathology of this interesting neoplasm. This review charts particular aspects in the field of cell cultures and tumor xenografts in nude mice in GIST and their implication in the establishment of appropriate models for discovering and testing therapy. The cytogenetic features of these tumors are also discussed. Classic karyotyping, loss of heterozygosity, fluorescent in situ hybridization, comparative genomic hybridization (CGH), and CGH-array analyses have shown that chromosomal numerical abnormalities and loss of genetic material at chromosomes 1p, 9p, 14q, and 22q are significantly associated with GIST malignancy and response to treatment. Furthermore, these regions constitute "hot" areas for finding candidate genes involved in the pathogenesis of GISTs. A deeper knowledge of these genetic aspects of GIST will provide a better understanding of this neoplasm that could translate into clinical practice.


Genetic interactions between a phospholipase A2 and the Rim101 pathway components in S. cerevisiae reveal a role for this pathway in response to changes in membrane composition and shape.
Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A(2) (PLA(2)s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA(2) in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA(2) activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA(2) activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them.


Development of a host-vector system for Lactobacillus plantarum L137 isolated from a traditional fermented food produced in the Philippines.
Lactobacillus plantarum NC13, a strain derived from the L. plantarum strain L137 isolated from a traditional fermented food produced in the Philippines, contains 9 of the 15 plasmids in the parental strain. To construct a shuttle vector between L. plantarum and Escherichia coli for genetic manipulation of L137 and its derivatives, recombinant plasmids were prepared by using the 9-plasmid DNA mixture and an E. coli vector, pBluescript II SK+. The resultant recombinant plasmids were re-transferred to L. plantarum NCL21, an NC13-derived strain cured of 3 of the 9 plasmids, and 3 recombinant plasmids were obtained. The smallest plasmid, pRN14, contained a small cryptic plasmid, pLTK2, which is one of the plasmids in L. plantarum L137. Thus, the complete nucleotide sequence of pLTK2 was determined. The pLTK2 is 2295 bp in length, and has a major open reading frame of 951 bp. An encoded sequence of 317-amino acids showed extensive similarity with genes encoding replication protein (repA). A putative replication origin in pLTK2 also showed high homology to those of other gram-positive bacterial plasmids that replicate by the rolling circle mechanism. The shuttle vector pRN14 contained the erythromycin resistance gene and the ColE1 and pLTK2 replication origins. Transformation of L. plantarum strains with pRN14 by electroporation was optimized to give a transformation efficiency of 2 x 10(4) transformants/ mug plasmid. Plasmid pRN14 was stably maintained in strain NCL21, as well as in L. casei K95-5.


Cyclosporine A neurotoxicity among bone marrow transplant recipients.
Cyclosporine A (CsA) neurotoxicity is an iatrogenic disease with significant morbidity and occasional mortality. We retrospectively reviewed the cases of CsA neurotoxicity among bone marrow transplant recipients at our institution, and summarized the current literature on the subject. The neurologic presentation is varied and the neurologic manifestations are reversible, even after prolonged toxicity, in most instances. Serum CsA level is useful in evaluation, as the level is high in most instances. However, in a case of suspected neurotoxicity, withdrawal of the drug is the only way of determining presence or absence of such toxicity. The electrophysiologic studies, especially electroencephalogram (EEG), is very sensitive in identifying the problem, but lacks specificity. On the other hand, the neuroimaging studies are helpful in making a diagnosis if they show characteristic findings of hyperintense lesions affecting posterior cerebral regions on T2 weighted magnetic resonance images (MRI) or white matter hypodensities on computed tomographic (CT) scan. These lesions are probably due to breakdown of blood-brain barrier resulting in leakage of fluid in interstitial space. The breakdown could be serious enough to cause microhemorrhages that may coalesce to produce macrohemorrhages.


Lack of dose rate modification (0.0049 vs. 0.12 Gy/min) of fission-neutron-induced neoplastic transformation in C3H/10T1/2 cells.
Clonogenic survival and neoplastic transformation of asynchronous cultures of C3H/10T1/2 cells were used to assay the effect of dose protraction of reactor-produced fission neutrons. Cells were exposed to eight neutron doses ranging from 0.05 to 0.9 Gy delivered at 11.7 or at 0.49 cGy/min. For each dose level, high and low dose rate irradiations were performed on the same day. At each dose a similar effectiveness of fission neutron irradiation at high or low dose rates was measured for both cell survival and transformation. The combined high and low dose-rate data were analysed by two- or three-parameter models. Depending on the model used, values of the effectiveness per unit dose derived as parameters of linear terms of the respective dose-response curves were 0.9-1.2 Gy-1 for clonogenic survival and 5-8 x 10(-4) Gy-1 for neoplastic transformation. It is concluded that the modification of fission neutron dose-response curves by dose rate is negligible or absent in the range of doses and dose rates examined, in contrast to results with other sources of fission or fast neutrons.


Isolation and Characterization of Yeast with Benzenemethanethiol Synthesis Ability Isolated from Baijiu Daqu.
Baijiu, a prevalent alcoholic beverage, boasts over 2000 aroma compounds, with sulfur-containing compounds being the most influential in shaping its flavor. Benzenemethanethiol, a distinctive odorant in baijiu, is known to enhance the holistic flavor profile of baijiu. Despite its importance, there is very little literature on the biotransformation mechanism of benzenemethanethiol. Thus, extensive research efforts have been made to elucidate the formation mechanism of this compound in order to improve baijiu production. In this study, 12 yeast strains capable of generating benzenemethanethiol were isolated from baijiu daqu, and the Saccharomyces cerevisiae strain J14 was selected for further investigation. The fermentation conditions were optimized, and it was found that the optimal conditions for producing benzenemethanethiol were at 28 °C for 24 h with a 4% (v/v) inoculum of 3.025 g/L L-cysteine. This is the first time that yeast has been shown to produce benzenemethanethiol isolated from the baijiu fermentation system. These findings also suggest that benzenemethanethiol can be metabolized by yeast using L-cysteine and benzaldehyde as precursor substrates.


A Rare Olive Compound Oleacein Improves Lipid and Glucose Metabolism, and Inflammatory Functions: A Comprehensive Whole-Genome Transcriptomics Analysis in Adipocytes Differentiated from Healthy and Diabetic Adipose Stem Cells.
Oleacein (OLE), a rare natural compound found in unfiltered extra virgin olive oil, has been shown to have anti-inflammatory and anti-obesity properties. However, little is known regarding the mechanisms by which OLE influences metabolic processes linked to disease targets, particularly in the context of lipid metabolism. In the present study, we conducted whole-genome DNA microarray analyses in adipocytes differentiated from human adipose-derived stem cells (hASCs) and diabetic hASCs (d-hASCs) to examine the effects of OLE on modulating metabolic pathways. We found that OLE significantly inhibited lipid formation in adipocytes differentiated from both sources. In addition, microarray analysis demonstrated that OLE treatment could significantly downregulate lipid-metabolism-related genes and modulate glucose metabolism in both adipocyte groups. Transcription factor enrichment and protein-protein interaction (PPI) analyses identified potential regulatory gene targets. We also found that OLE treatment enhanced the anti-inflammatory properties in adipocytes. Our study findings suggest that OLE exhibits potential benefits in improving lipid and glucose metabolism, thus holding promise for its application in the management of metabolic disorders.


[Current concepts in the management of pyogenic brain abscesses].
Brain abscesses are severe infections with lethal outcome in the case of delay in diagnosis and treatment. The authors report their experience about 30 patients with pyogenic brain abscesses treated between 1989 and 2000. The goal of the study is to analyse epidemiological, clinical and therapeutic aspects of this disease. The sex ratio (M:W) was 2,3 and the mean age was 34 years. Predisposing factors were sepsis of adjacent organs (53%) and bacteremia (30%). The clinical manifestations were: fever (83%), headaches (90%) and focal neurologic signs (57%). CT-scan findings were single lesions in 80% of cases. CT-scan showed a deep ring-enhancing lesion with surrounding edema in 77% of cases. Bacteriological agents in 13 cases (43%) were: 4 Staphylococcus aureus, 2 Neisseria meningitidis and 7 negative Gram bacilli. Medical treatment alone was in 77% of cases; seven patients benefited from medical and neurosurgical approaches. Death occured in 10% of cases.


Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane.
The microlocalization of Ras proteins to different microdomains of the plasma membrane is critical for signaling specificity. Here we examine the complex membrane interactions of H-ras with a combination of FRAP on live cells to measure membrane affinity and electron microscopy of intact plasma membrane sheets to spatially map microdomains. We show that three separable forces operate on H-ras at the plasma membrane. The lipid anchor, comprising a processed CAAX motif and two palmitic acid residues, generates one attractive force that provides a high-affinity interaction with lipid rafts. The adjacent hypervariable linker domain provides a second attractive force but for nonraft plasma membrane microdomains. Operating against the attractive interaction of the lipid anchor for lipid rafts is a repulsive force generated by the N-terminal catalytic domain that increases when H-ras is GTP loaded. These observations lead directly to a novel mechanism that explains how H-ras lateral segregation is regulated by activation state: GTP loading decreases H-ras affinity for lipid rafts and allows the hypervariable linker domain to target to nonraft microdomains, the primary site of H-ras signaling.


Plasma active renin, inactive renin and kallikrein in patients with disseminated intravascular coagulation.
To investigate the role plasma kallikrein plays in the in vivo activation of inactive renin, we measured plasma active renin, inactive renin, kallikrein and prekallikrein levels in 10 patients with disseminated intravascular coagulation (DIC), with 16 normal persons as controls. The plasma active renin concentration was expressed by the angiotensin I generation rate after the addition of sheep renin substrate. Plasma inactive renin was activated by trypsin. The plasma total kallikrein level was measured by an assay of kallikrein activity on synthetic substrate S-2302 after the addition of a prekallikrein activator. Plasma kallikrein was assayed by its activity on S-2302 without addition of the activator. The prekallikrein level was obtained by subtracting the kallikrein activity from the total kallikrein activity. A significant decrease in the plasma prekallikrein concentration was observed in DIC patients, as compared to that of controls (p less than 0.01). There was no significant difference in plasma levels of kallikrein, inactive renin, and the proportion of active renin between DIC patients and normal controls, but the active renin level was higher in DIC patients. There was no significant correlation between the level of plasma kallikrein and the proportion of active renin in either normal controls or DIC patients. These results are compatible with, but do not prove, the theory that plasma kallikrein plays a role in the in vivo activation of inactive renin.


Live nondirected uterus donors: Psychological characteristics and motivation for donation.
Emerging research suggests that uterus transplantation is a viable option for women without a uterus who want to become pregnant and carry a child to term. Currently, no knowledge exists regarding nondirected uterus donors. This study (NCT 02656550) explored the baseline psychological characteristics of nondirected uterus donors at a single study site. Of the 62 potential donors who underwent initial screening, 6 nondirected donors were chosen and participated in uterus donation. Participants received a comprehensive evaluation, which included clinical history and psychological assessments. The mean age of the donors was 42 years; most (83%) were white/not Hispanic, and all had a college degree. Current depression was reported by 2 participants, past depression was reported in 2 participants, and past anxiety was reported in 3 participants. Based on several different psychological measures, donors had a higher general well-being than the normative sample, and none of the participants' scores indicated psychological distress. All 6 women indicated that giving another woman an opportunity to carry her own child was a motivation for pursuing uterus donation. Further research on potential psychological motives and gains for the donor as well as long-term effects on donors is crucial for ethical practice.


The endosomal Q-SNARE, Syntaxin 7, defines a rapidly replenishing synaptic vesicle recycling pool in hippocampal neurons.
Upon the arrival of repetitive stimulation at the presynaptic terminals of neurons, replenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained neurotransmitter release. Kinetics of replenishment and the available pool size define synaptic performance. However, whether all SVs in the recycling pool are recruited for release with equal probability and speed is unknown. Here, based on comprehensive optical imaging of various presynaptic endosomal SNARE proteins in cultured hippocampal neurons, all of which are implicated in organellar membrane fusion in non-neuronal cells, we show that part of the recycling pool bearing the endosomal Q-SNARE, syntaxin 7 (Stx7), is preferentially mobilized for release during high-frequency repetitive stimulation. Recruitment of the SV pool marked with an Stx7-reporter requires actin polymerization, as well as activation of the Ca2+/calmodulin signaling pathway, reminiscent of rapidly replenishing SVs characterized previously in calyx of Held synapses. Furthermore, disruption of Stx7 function by overexpressing its N-terminal domain selectively abolished this pool. Thus, our data indicate that endosomal membrane fusion involving Stx7 forms rapidly replenishing vesicles essential for synaptic responses to high-frequency repetitive stimulation, and also highlight functional diversities of endosomal SNAREs in generating distinct exocytic vesicles in the presynaptic terminals.


Delayed discharge at the heart of the NHS crisis.
There are no winners when a patient's discharge from hospital is delayed. The frustration is felt by the patient, their family and the healthcare professionals caring for the patient. Ultimately, the entire health system is affected, as a badly-needed bed can't be used for other patients.


The glutamate-isolated mass receptor potential of the frog's retina. III. Calcium dependence.
The mass receptor potential of excised frog retinas was isolated by superfusion of the tissue with modified Ringer solutions containing sodium glutamate. The changes in the potential amplitude due to the variation of the calcium concentration were measured. Step by step reduction of the calcium concentration from 2 to 0.05 mM caused a mass receptor potential increase up to threefold; further calcium lowering diminished the amplitudes. Rods and cones, however, seemed to react in different ways to changed calcium concentrations. The responses to red light stimuli and the so-called rapid decay of the glutamate-isolated potentials, both generated mainly by cones, disappeared in calcium free solutions. Both the responses to green light stimuli and the so-called remaining part of mass receptor potentials, however, i.e. the potentials produced mainly by rods, were still larger in calcium free solutions compared to those in 2 mM calcium solutions. Changing the calcium concentration of the solutions altered both the Sodium and the potassium dependence of the mass receptor potential, and that differently for rods und cones. The results are used to support the hypothesis that calcium acts as internal transmitter in vertebrate photoreceptors. This view is confirmed by interpretation and critical comparison of data taken from the literature.


Domestic violence during pregnancy and risk of low birthweight and maternal complications: a prospective cohort study at Mulago Hospital, Uganda.
To investigate whether domestic violence during pregnancy is a risk factor for antepartum hospitalization or low birthweight (LBW) delivery. A prospective cohort study was conducted in Mulago hospital, Kampala, Uganda, among 612 women recruited in the second pregnancy trimester and followed up to delivery, from May 2004 through July 2005. The exposure (physical, sexual or psychological violence during pregnancy) was assessed using the Abuse Assessment Screen. The relative and attributable risks of LBW and antepartum hospitalization were estimated using multivariate logistic regression analysis. The 169 women [27.7% 95% CI (24.3-31.5%)] who reported domestic violence during pregnancy did not differ significantly from the unexposed regarding sociodemographic characteristics, but differed significantly (P < 0.05) regarding domicile variables (had less household decision-making power, more resided in extended families and more had unplanned pregnancy). They delivered babies with a mean birthweight 2647.5 +/- 604 g, on average 186 g [(95% CI 76-296); P = 0.001] lower than those unexposed. After adjusting for age, parity, number of living children, pregnancy planning, domicile and number of years in marriage, the relative risk (RR) of LBW delivery among women exposed to domestic violence was 3.78 (95% CI 2.86-5.00). Such women had a 37% higher risk of obstetric complications (such as hypertension, premature rupture of membranes and anaemia) that necessitated antepartum hospitalization [RR 1.37 (95% CI 1.01-1.84)]. In this pregnancy cohort, domestic violence during pregnancy was a risk factor for LBW delivery and antepartum hospitalization.


Molecular design of anticancer drug leads based on three-dimensional quantitative structure-activity relationship.
Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.


A rational approach to diagnosis and treatment of intermittent claudication.
Intermittent claudication (IC), the first recognizable symptom of peripheral arterial disease, is prevalent among older persons and associated with significant morbidity and mortality. The diagnosis of IC involves taking a thorough patient history, conducting a physical examination with an emphasis on the cardiovascular system, and noninvasive testing with functional assessment. The goals of treatment for IC are to prevent progression of vascular disease and cardiovascular complications and to improve exercise performance, functional status, and quality of life. The cornerstones of therapy are risk-factor modification, particularly smoking cessation, and exercise. In patients for whom non-pharmacologic therapy does not provide adequate pain relief and improvement in physical function, medical therapy with 1 of 2 drugs approved for the treatment of IC may be appropriate. Revascularization or intervention is generally reserved for patients with incapacitating disease. Early diagnosis of IC and implementation of effective therapy can reduce the development of morbidity and mortality.


Measuring Professional Values Among Jordanian and Palestinian Undergraduate Nursing Students: A Comparative Study.
Professional values provide a road map for guiding the behaviors of nursing students during practice and are considered standards for acceptable actions during the provision of nursing care. Nursing educators play a vital role in helping their students embrace professional values in their future career. This study was designed to assess and compare professional values among Jordanian and Palestinian undergraduate nursing students. In this descriptive, cross-sectional study, 182 Jordanian and 353 Palestinian nursing students completed the Nurses Professional Values Scale-Revised (NPVS-R), which covers five domains (caring, trust, justice, activism, and professionalism). The mean age of the participants was 22.5 years, and most (56.6%) were female. The mean total score for the NPVS-R was 3.85, with the "justice" dimension receiving the highest mean score (4.07) and the "activism" dimension receiving the lowest mean score (3.63). The differences in mean NPVS-R total and dimension scores between the Jordanian and Palestinian students were not statistically significant. The results of this study support that Jordanian and Palestinian undergraduate nursing students have an acceptable level of professional values, with the NPVS-R justice domain scoring relatively high and the NPVS-R activism domain scoring relatively low. The authors hope that the results of this study encourage nursing educators to continue improving professional values among their students, especially with regard to the relatively low-rated dimensions.


Considering Tort Liability for Breaches to Privacy of Patient Data-- Managing Risks of Applicability of Privacy Torts, and Especially the Tort of "Intrusion on Seclusion" in the Health Context.
The mobile revolution is a watershed event across many fields, including health care. Now, electronic data storage, digital photography, smart phones and tablet devices present new opportunities for educators, researchers, and health care providers. Mobile technologies allow for new possibilities for physician collaboration as well as patient diagnosis, treatment and study. However, while it presents new opportunities, the mobile technological revolution in health care has brought about new risks to patient privacy. These risks to patients, in turn, translate into exposure to liability on the part of health care providers including physicians, allied health care professionals and institutions. This paper reviews recent developments in the legal landscape providing new forms of civil liability for breaches of privacy and discusses how risks of liability under those developing civil causes of action can be managed by health care providers, while they at the same time harness the potential of the mobile technological tide.


[Plasmapheresis in acute phase of multiple sclerosis and neuromyelitis optica].
In acute phase of multiple sclerosis (MS) and neuromyelitis optica (NMO), plasmapheresis (PP) should be considered as the 2nd choice treatment when corticosteroid pulse therapy results in unsuccessful. It is believed that the beneficial effects of PP occur through the elimination of pathogenic humoral and plasma factors, including autoantibodies, complement components, and cytokines. In MS, several clinical trials have shown the efficacy. However, there have been no randomized controlled trials that demonstrated the efficacy of PP in NMO. There are three methods of PP, plasma exchange, double filtration plasmapheresis and immunoadsorption plasmapheresis, available in Japan. But the difference of efficacy among these 3 methods has not been fully evaluated.


[The mechanism of the proaggregant action on the thrombocytes of RNA and DNA molecules].
The entrance of extracellular Ca2+ in ADP-stimulated human platelets and phospholipase A2 activity have been studied under the action of Ca precipitates DNA, RNA and dsRNA. The nucleic acids and its Ca complexes (Ca-NA) have been found to induce the aggregation of isolated human platelets by stimulation of extracellular Ca2+ entrance into the platelets and the formation of phosphatidilcholine and phosphatidilethanolamine lysoderivatives having the membranolytic effect.


Psychologic and biologic factors associated with fatigue in patients with persistent radiculopathy.
Fatigue is a common symptom associated with neuropathic pain (NP) and can have negative consequences on psychosocial functioning, physical endurance, and quality of life. Recent evidence indicates that immune activation modulated through the increased release of proinflammatory cytokines can predict fatigue in some patient populations. Although earlier studies have shown that immune activation is a pathophysiologic feature of NP, there have been no studies to examine the relationship between immune activation and fatigue in persons with NP. Therefore, the purpose of this exploratory study was to: 1) determine the relationships among fatigue, pain, psychosocial factors, and selected biologic markers of immune activation (interleukin [IL] 6 and soluble IL-6 receptor [sIL-6R]) in participants with persistent radiculopathy; and 2) determine the differences in these variables based on fatigue severity. Participants (n = 80) were classified according to their level of fatigue as low (27.5%), moderate (32.5%), or high (40%), and significant differences were found between fatigue categories (p = .001). Multivariate analyses of variance revealed that individuals with moderate to high levels of fatigue differed from those with the lowest levels of fatigue in psychologic distress, depressive symptoms, IL-6, and sIL-6R, whereas the differences between moderate and high levels of fatigue were significant for psychologic distress and sIL-6R only. The findings suggest that immune activation affects fatigue severity and possibly other behavioral responses, offering important information when providing care to patients with persistent radiculopathy. The integration of biobehavioral nursing interventions in pain management may have a greater impact on quality of life than treatment focused only on pain.


L-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway.
L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. L-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 μmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 μmol L-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70S6K and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.


Response of lactate metabolism in brain glucosensing areas of rainbow trout (Oncorhynchus mykiss) to changes in glucose levels.
There is no evidence in fish brain demonstrating the existence of changes in lactate metabolism in response to alterations in glucose levels. We induced in rainbow trout through intraperitoneal (IP) treatments, hypoglycaemic or hyperglycaemic changes to assess the response of parameters involved in lactate metabolism in glucosensing areas like hypothalamus and hindbrain. To distinguish those effects from those induced by peripheral changes in the levels of metabolites or hormones, we also carried out intracerebroventricular (ICV) treatments with 2-deoxy-D-glucose (2-DG, a non-metabolizable glucose analogue thus inducing local glucopenia) or glucose. Finally, we also incubated hypothalamus and hindbrain in vitro in the presence of increased glucose concentrations. The changes in glucose availability were in general correlated to changes in the amount of lactate in both areas. However, when we assessed in these areas the response of parameters related to lactate metabolism, the results obtained were contradictory. The increase in glucose levels did not produce in general the expected changes in those pathways with only a minor increase in their capacity of lactate production. The decrease in glucose levels was, however, more clearly related to a decreased capacity of the pathways involved in the production and use of lactate, and this was especially evident after ICV treatment with 2-DG in both areas. In conclusion, the present results while addressing the existence of changes in lactate metabolism after inducing changes in glucose levels in brain glucosensing areas only partially support the possible existence of an astrocyte-neuron lactate shuttle in hypothalamus and hindbrain of rainbow trout relating glucose availability to lactate production and use.


[A case of malignant perivascular epithelioid cell tumor of the retroperitoneum with multiple metastases].
Perivascular epithelioid cell tumors (PEComas) are unusual mesenchymal neoplasms composed of histologically and immunohistochemically distinct perivascular epithelioid cells (PECs). Although PEComas have the potential to behave in a malignant fashion, malignant PEComas arising from the retroperitoneum are extremely rare. A 68-year-old woman presented with a painful palpable mass in her left upper abdomen. Computed tomography of the abdomen showed a 9 cm sized heterogeneous mass in left para-aortic space and multiple hypervascular nodules in the liver. (18)F-fludeoxyglucose-PET/CT showed multifocal hyper-metabolic lesions in retroperitoneum, liver, and skeletal bones. Percutaneous needle biopsies were done on the retroperitoneal and hepatic mass. Both specimens were positive for human melanoma black-45 (HMB-45) on histological and immunohistochemical staining which was compatible with PEComas. Herein, we report a rare case of retroperitoneal PEComa with multiple metastases involving liver and bone at initial diagnosis that exhibited aggressive behavior and resulted in a devastating prognosis.


Aerobic training prevents oxidative profile and improves nitric oxide and vascular reactivity in rats with cardiometabolic alteration.
Cardiovascular disease is the major cause of death worldwide; therefore it is important to understand the natural history of the pathophysiologic process and develop strategies to halt its progression. Thus this study investigated the protective effect of aerobic training on pathophysiological mechanisms involved in subclinical cardiometabolic alterations in a model with constant exposure to a prejudicial agent. Male Wistar rats were divided into a control group (C), which received drinking water, fructose group (F), which was fed 10% fructose in drinking water for 10 wk, and control training (CT) and fructose training groups (FT), in which moderate aerobic training was added in the last 8 wk of the study. Insulin, triacylglycerol, and isoprostane were higher and superoxide dismutase (SOD) was lower in the F group. There was no difference in thoracic aorta histology, but a decreased vascularization was seen in the F group, avoided by training in left ventricle. Regarding vascular function, the F group exhibited increased vasoconstrictory reactivity to phenylephrine. The F group presented impaired vasodilation to acetylcholine. Regarding endothelial nitric oxide synthase (eNOS), the F group presented a lower expression, and phosphorylated eNOS was higher in the trained groups than in their respective control groups. This same pattern was observed for nitric oxide bioavailability, antioxidant protein expression in aorta, left ventricle, and muscle (catalase, SOD, and glutathione peroxidase), serum SOD activity, and muscle mass. These results suggest that exercise training enhanced the antioxidant pathway and, as a consequence, the eNOS pathway, preventing an impairment in vascular vasodilatory capacity.


The aetiological relationship between depressive symptoms and health-related quality of life: A population-based twin study in Sri Lanka.
Depression often co-occurs with poor health-related quality of life (HRQL). Twin studies report genetic and individual-level environmental underpinnings in the aetiology of both depression and HRQL, but there is limited twin research exploring this association further. There is also little evidence on sex differences and non-Western populations are underrepresented. In this paper we explored the phenotypic and aetiological relationship between depressive symptoms and HRQL and possible sex differences in a low-middle-income Sri Lankan population. Data for 3,948 participants came from the Colombo Twin and Singleton Follow-up Study (CoTaSS-2). Using self-report measures of depressive symptoms and HRQL, we conducted univariate and bivariate sex-limitation twin analyses. Depressive symptoms showed moderate genetic (33%) and strong nonshared environmental influences (67%). Nonshared environment accounted for the majority of variance in all the subscales of HRQL (ranging from 68 to 93%), alongside small genetic influences (ranging from 0 to 23%) and shared environmental influences (ranging from 0 to 28%). Genetic influences were significant for emotional wellbeing (23%). Shared environmental influences were significant for four out of the eight HRQL variables (ranging from 22-28%), and they were more prominent in females than males. Depressive symptoms were significantly associated with lower HRQL scores. These correlations were mostly explained by overlapping nonshared environmental effects. For traits related to emotional functioning, we also detected substantial overlapping genetic influences with depressive symptoms. Our study confirmed previous findings of a negative association between depressive symptoms and HRQL. However, some of the aetiological factors of HRQL differed from Western studies, particularly regarding the effects of shared environment. Our findings highlight the importance of cross-cultural research in understanding associations between psychological wellbeing and HRQL.


Haemostatic changes and acquired activated protein C resistance in normal pregnancy.
Influence of changes in levels of coagulation factors and anticoagulants on acquired activated protein C (APC) resistance were studied in 40 healthy women during normal pregnancy. Factor VIII (FVIII), von Willebrand factor antigen (VWF:Ag), free protein S (FPS) and protein C were determined at 5-13, 14-26 and 27-40 weeks gestation and more than 6 weeks postpartum. APC anticoagulant activity was determined by measuring the activated partial thromboplastin time before and after adding human APC, expressed as the APC-sensitivity ratio (APC-SR). During the second and third gestation trimesters a significant increase (P < 0.05) in FVIII and VWF:Ag levels and a decrease in FPS levels were seen compared with the first trimester. Postpartum FVIII and VWF:Ag levels significantly decreased and FPS levels increased compared with the third trimester. Protein C levels remained unchanged during pregnancy and postpartum. Between increased FVIII and lowered APC-SR a trend of inverse correlation (r = -0.329; P = 0.076) occurred in the second trimester. No correlation was found between APC-SR and FPS or VWF:Ag levels. A remarkable finding is the strong inverse relationship between APC-SR and protein C levels (r <or= -0.392; P < 0.05) during pregnancy and postpartum. This may indicate that anticoagulant activity of added human APC measured by activated partial thromboplastin time is diminished in the presence of high endogenous protein C levels. A possible hypothesis is steric hindrance by sample protein C of APC binding sites on target activated factor V and/or cofactor protein S. The clinical significance of this finding should be determined because it complicates the interpretation of lowered APC-SR.


Chiral Indolizidine Synthesis through the Ir-Catalyzed Asymmetric Hydrogenation of Cyclic Pyridinium Salts.
The Ir-catalyzed asymmetric hydrogenation of cyclic pyridinium salts is presented as a new strategy for the convenient and efficient synthesis of chiral indolizidines. The asymmetric hydrogenation of cyclic pyridinium salts derived from 2-(2-acylphenyl)pyridines proceeded smoothly in the presence of [Ir(cod)Cl]2 and (R)-DM-SegPhos to provide the desired chiral 7,8-benzoindolizidines 6 in high to excellent yields with moderate enantioselectivity (up to 86:14 er) and excellent diastereoselectivity (>20:1 dr). The enantiomeric purity of 6j was increased to 92:8 through recrystallization.


Treatment planning of implants when 3 mandibular posterior teeth are missing: a 3-dimensional finite element analysis.
To analyze the biomechanics of 3 designs of implant treatment for 3 teeth missing in posterior low arch quadrants. A posterior portion of the human mandible missing 44, 45, 46 and three 4.1 × 10 mm threaded ITI implants with crowns were used to construct the finite element model. According to 3 implants being single, splinted or 2 implants support fixed partial denture (FPD) fixed in bone segments. Three implant support conditions were prepared with ANSYS 10.0. A load of 100 N was applied at the central fossa of the occlusal surfaces of the crowns at 45 degrees buccolingually along the triangular ridge of the buccal cusp. The von Mises stress and strain distributions in periimplant bone were observed. The results demonstrated that the von Mises stress in the supporting bone of the 2-implant supported FPD significantly increased compared with that in the 3-implant replacement. Meanwhile, when 3 implants were splinted, only the median implant had a decreased and more homogenous stress distribution, and the other implants did not exhibit significant differences when splinted. This study suggests that when space and cost permit, a 2-implant supported FPD should not be used, and 1 implant for each missing tooth being single is recommended.


Double-stranded ribonucleic acid in Agaricus bisporus.
Double-stranded ribonucleic acid present in virus-infected mushrooms of Agaricus bisporus has been resolved through polyacrylamide gel electrophoresis into six molecular-weight forms. Identification of these six double-stranded ribonucleic acids in mushrooms by this procedure has proven to be a useful and diagnostic method for viral infection in the cultivated mushroom.


Juzentaihoto Suppresses Muscle Atrophy in Streptozotocin-Induced Diabetic Mice.
In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.


Effects of different fungicide treatments on grape, must and wine quality.
The aim of this study was to evaluate the effectiveness of natural products and low-rate copper formulations against grapevine downy mildew, in order to reduce or replace copper use in organic farming, and to assess the effects on the qualitative parameters of grape, must and wine of the different treatments. The trial was carried out in an organic vineyard in accordance with the EPPO/OEPP guidelines. Plots were prepared, each containing 12 vine-plants and repeated four times in randomized blocks. At harvest, representative grape samples were picked off from the plots treated with the different products: for each treatment, a random sub-sample was kept for analyses, the remaining part was processed to produce wine. Grapes, musts and wines were characterized for their food quality indices, as well as for their nutraceutical profiles and antioxidant activity. On must and wine, sugars, acidity and pH were determined according to official methods. On grape and wine, total polyphenol, flavonoid and hydroxycinnamic acid contents were determined by spectrophotometric analysis, as well as antioxidant activity tests. Organic acids and single polyphenols were also determined by HPLC. The results of the trial, characterized by moderate infection pressure, indicate that all tested products guaranteed a satisfactory control of Plasmopara viticola although the alternatives to copper were not as effective as copper. Data evidence that grape quality and its oenological potential were not significantly influenced by applied treatments and that they did not significantly differ in comparison with the untreated control, only with an interesting significant negative correlation between proanthocyanidins level and the severity of disease on ripe berries. The uniformity of data seems to evidence a general adaptation of plants to different treatment stresses, probably due both to low input of active ingredients and to moderate downy mildew infection.