Vibrational polariton transport in disordered media.
Chemical reactions and energy transport phenomena have been experimentally reported to be significantly affected by strong light-matter interactions and vibrational polariton formation. These quasiparticles exhibit nontrivial transport phenomena due to the long-range correlations induced by the photonic system and elastic and inelastic scattering processes driven by matter disorder. In this article, we employ the Ioffe-Regel criterion to obtain vibrational polariton mobility edges and to identify distinct regimes of delocalization and transport under variable experimental conditions of light-matter detuning, disorder, and interaction strength. Correlations between the obtained trends and recent observations of polariton effects on reactivity are discussed, and essential differences between transport phenomena in organic electronic exciton and vibrational polaritons are highlighted. Our transport diagrams show the rich diversity of transport phenomena under vibrational strong coupling and indicate that macroscopic delocalization is favored at negative detuning and large light-matter interaction strength. We also find the surprising feature that, despite the presence of dephasing-induced inelastic scattering processes, macroscopic lower polariton delocalization and wave transport are expected to persist experimentally, even in modes with small photonic weight.


Generation and Characterization of Murine Oral Mucosal Organoid Cultures.
The mucous lining covering the inside of our mouth, the oral mucosa, is a highly compartmentalized tissue and can be subdivided into the buccal mucosa, gingiva, lips, palate, and tongue. Its uppermost layer, the oral epithelium, is maintained by adult stem cells throughout life. Proliferation and differentiation of adult epithelial stem cells have been intensively studied using in vivo mouse models as well as two-dimensional (2D) feeder-cell based in vitro models. Complementary to these methods is organoid technology, where adult stem cells are embedded into an extracellular matrix (ECM)-rich hydrogel and provided with a culture medium containing a defined cocktail of growth factors. Under these conditions, adult stem cells proliferate and spontaneously form three-dimensional (3D) cell clusters, the so-called organoids. Organoid cultures were initially established from murine small intestinal epithelial stem cells. However, the method has since been adapted for other epithelial stem cell types. Here, we describe a protocol for the generation and characterization of murine oral mucosal organoid cultures. Primary epithelial cells are isolated from murine tongue tissue, embedded into an ECM hydrogel, and cultured in a medium containing: epidermal growth factor (EGF), R-spondin, and fibroblast growth factor (FGF) 10. Within 7 to 14 days of initial seeding, the resulting organoids can be passaged for further expansion and cryopreservation. We additionally present strategies for the characterization of established organoid cultures via 3D whole-mount imaging and gene-expression analysis. This protocol may serve as a tool to investigate oral epithelial stem cell behavior ex vivo in a reductionist manner.


A novel solution process for the synthesis of VO2 thin films with excellent thermochromic properties.
This article describes a novel and simple route to preparing VO(2) thermochromic films by using a VOCl(2) solution with poly(vinylpyrrolidone) (PVP). X-ray diffraction and Raman spectra showed that the VO(2) films deposited with PVP consisted of a nearly pure monoclinic/rutile (M/R) phase. Conversely, films prepared without PVP contained obviously impure crystalline phases. The as-prepared films with PVP showed excellent optical properties compared to those prepared by common gas-phase methods: an integral visible transmittance of 54.5% and an IR reduction (change in transmittance) of 41.5% at 2000 nm. The phase-transition temperatures were adjusted from 69 to 54 degrees C by tungsten doping. Equipment analyses revealed that PVP plays two roles in the film formation. First, it fundamentally acts as a film-forming promoter to improve physical gelation via interactions among oppositely charged carbonyl groups and amine groups of the polymer. Second, the negatively charged carbonyl groups can interact with VO(2+) to form a uniform mixed-gel film after solvent evaporation. Thus, the addition of PVP can stabilize the solution and improve the as-prepared film quality and phase purity. The current study suggests that the process has promise in applications of smart windows.


One of the hottest topics in epileptology: ABC proteins. Their inhibition may be the future for patients with intractable seizures.
One of the new topics in epileptology is the ABC proteins, which seem to control whether or not anti-epileptic drugs (AEDs) can come in contact with and affect the epileptogenic areas that cause seizures. The goal of this report is to simplify the concepts involved in these proteins and then to review the progress made in the field, especially of one protein called P-glycoprotein (P-gp). First, the ABC proteins are reviewed, mainly P-gp, which appears to alter drug permeability (like an extra blood-brain barrier). The possibility is discussed that changes in P-gp are the result of many seizures; are caused by the AEDs, or truly reflect pharmacoresistance. The different locations where these changes can be seen include the endothelial cells, glia and also neurons. The polymorphism of P-gp, called C3435T, probably has little functional significance and finally the importance of inhibitors of P-g to reverse pharmacoresistance is emphasized. Tariquidar (XR9576) is likely to be a good candidate that appears to inhibit these proteins and therefore to allow the AEDs to control the intractable seizures that may account for nearly 40% of our patients.


Pericytes or Mesenchymal Stem Cells: Is That the Question?
For almost a decade, mesenchymal stem cells (MSCs) were believed to reside as perivascular cells in vivo. In this issue of Cell Stem Cell, Guimarães-Camboa et al. (2017) challenge this idea and use lineage tracing to demonstrate that perivascular cells do not behave as tissue-specific progenitors in various organs, despite showing MSC potential in vitro.


Diagnosis, prognosis and management of erythrodermic cutaneous T-cell lymphoma.
Erythroderma describes complete or near-complete skin surface erythema of any cause. Cutaneous T-cell lymphoma accounts for a minority of cases of erythroderma and consists of erythrodermic mycosis fungoides, Sézary syndrome. Both adult T-cell leukemia/lymphoma and T-cell prolymphocytic leukemia can also rarely present with erythroderma. Diagnosis may be extremely challenging because benign disorders may have overlapping features with those of lymphoma. Prognosis is poor with median survival of approximately 2 years. The evidence base for therapeutic approaches relies on cohorts and case series and more recently Phase II trials. Improved patient selection and identification of appropriate conditioning regimens for reduced intensity allogeneic hematopoetic transplant are likely to improve survival, although a significant number of patients may not be fit for transplant because of advanced age and comorbidities.


Management of acute ischemic stroke due to tandem occlusion: should endovascular recanalization of the extracranial or intracranial occlusive lesion be done first?
OBJECTIVE Acute tandem occlusions of the cervical internal carotid artery and an intracranial large vessel present treatment challenges. Controversy exists regarding which lesion should be addressed first. The authors sought to evaluate the endovascular approach for revascularization of these lesions at Gates Vascular Institute. METHODS The authors performed a retrospective review of a prospectively maintained, single-institution database. They analyzed demographic, procedural, radiological, and clinical outcome data for patients who underwent endovascular treatment for tandem occlusions. A modified Rankin Scale (mRS) score ≤ 2 was defined as a favorable clinical outcome. RESULTS Forty-five patients were identified for inclusion in the study. The average age of these patients was 64 years; the mean National Institutes of Health Stroke Scale score at presentation was 14.4. Fifteen patients received intravenous thrombolysis before undergoing endovascular treatment. Thirty-seven (82%) of the 45 proximal cervical internal carotid artery occlusions were atherothrombotic in nature. Thirty-eight patients underwent a proximal-to-distal approach with carotid artery stenting first, followed by intracranial thrombectomy, whereas 7 patients underwent a distal-to-proximal approach (that is, intracranial thrombectomy was performed first). Thirty-seven (82%) procedures were completed with local anesthesia. For intracranial thrombectomy procedures, aspiration alone was used in 15 cases, stent retrieval alone was used in 5, and a combination of aspiration and stent-retriever thrombectomy was used in the remaining 25. The average time to revascularization was 81 minutes. Successful recanalization (thrombolysis in cerebral infarction Grade 2b/3) was achieved in 39 (87%) patients. Mean National Institutes of Health Stroke Scale scores were 9.3 immediately postprocedure (p < 0.05) (n = 31), 5.1 at discharge (p < 0.05) (n = 31), and 3.6 at 3 months (p < 0.05) (n = 30). There were 5 in-hospital deaths (11%); and 2 patients (4.4%) had symptomatic intracranial hemorrhage within 24 hours postprocedure. Favorable outcomes (mRS score ≤ 2) were achieved at 3 months in 22 (73.3%) of 30 patients available for follow-up, with an mRS score of 3 for 7 of 30 (23%) patients. CONCLUSIONS Tandem occlusions present treatment challenges, but high recanalization rates were possible in the present series using acute carotid artery stenting and mechanical thrombectomy concurrently. Proximal-to-distal and aspiration approaches were most commonly used because they were safe, efficacious, and feasible. Further study in the setting of a randomized controlled trial is needed to determine the best sequence for the treatment approach and the best technology for tandem occlusion.


Synthesis and characterization of AP5346, a novel polymer-linked diaminocyclohexyl platinum chemotherapeutic agent.
Syntheses of the novel polymer-bound platinum-based chemotherapeutic agent poly(HPMA)-GGG-Ama=Pt=(1R,2R)-DACH, AP5346, and its precursors are reported. The method utilized in preclinical development of AP5346 is described herein. Additionally, an improved synthesis, which has shown that ion exchange resins can be removed, significantly less platinum can be used when the reaction mixture is pH-stated, and the synthesis can be performed at a higher concentration, is reported. These combined improvements result in a more cost-effective, scaleable procedure. Various methods of analysis of the drug substance are also discussed. Specifically, (1)H NMR spectroscopy is used for identity and can also distinguish small molecule impurities to below 0.1%. (195)Pt NMR determines the coordination environment of the platinum and also identity and purity in relation to platinum chelation of the construct. Size exclusion chromatography is used to establish the molecular weight of AP5346 while ICP-AES determines platinum content and platinum release rates in phosphate-buffered saline. The cumulative results of this work have yielded an efficient syntheses of a polymer-based chemotherapeutic agent with subsequent detailed characterization methods.


Disseminated Mycobacterium avium complex in an immunocompetent host.
Disseminated Mycobacterium avium complex (DMAC) has historically been described in the immunocompromised. The current epidemiologic research suggests that the incidence of nontuberculous mycobacterial infections is increasing. We present a case of DMAC infection manifesting as hepatic granulomas in a 35-year-old immunocompetent female. This case suggests DMAC infection in a patient without traditional epidemiological risk factors.


Malagasy Polka Dot Moths (Noctuoidea: Erebidae: Arctiinae: Syntomini) of Ambohitantely-endemism in the most important relict of Central Plateau rainforest in Madagascar.
Malagasy Syntomini (Polka Dot Moths) are one of the largest endemic lineages of Lepidoptera on the island, belonging to the Tiger Moth subfamily (Arctiinae). This diverse radiation comprises nearly 100 valid described species that share a single ancestor. Despite a monograph in 1964 by Paul Griveaud, systematics of the group greatly needs modern revision, and their distribution on the island is still poorly known. This contribution concerns the diversity of Syntomini of the Réserve Spéciale d'Ambohitantely, which protects the largest remaining, but already highly fragmented, vestige of Central Plateau rainforest in Madagascar. Here we provide an annotated checklist of the eight species occurring in the Reserve. Two species are recorded from the forest for the first time, while five endemics are until now known only from Ambohitantely. We also describe for the first time the female of Thyrosticta vestigii Griveaud, 1964 and of Maculonaclia tampoketsya Griveaud, 1969, as well as a yellow morphotype of Thyrosticta dilata Griveaud, 1964, and we redescribe and illustrate the genitalia of the remaining species. The significance of such colour pattern variation in aposematic moths and the role of this Reserve as a local centre of diversity of Malagasy Syntomini together with its importance in the protection of the biodiversity of Madagascar are discussed.


Emerging issues in Israel: commentaries in a global context.
Communication disorders in Israel is a well-established professional field, requiring academic training and dual certification in speech pathology and audiology. Entry level is a BA in communication disorders (comparable to a MA degree in the USA) and 1 year of work under supervision. It is possible to continue studies towards higher degrees (MA and PhD). We face the same problems as in the rest of the world with need for trained professionals in the social services and the need to deal with multilingual and multicultural issues.


Kinetic and equilibrium alpha-secondary tritium isotope effects on reactions catalyzed by dCMP hydroxymethylase from bacteriophage T4.
Deoxycytidylate (dCMP) hydroxymethylase (CH) catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate (CH2THF). The nucleotide analog 5-fluorodeoxuridylate (FdUMP) stoichiometrically inactivates CH by formation of a covalent complex containing enzyme, FdUMP, and CH2THF. Similar FdUMP complexes are formed by dTMP synthase and dUMP hydroxymethylase, enzymes which are homologous to CH. Both the association and the dissociation rate of the FdUMP complex are shown to be increased by the mutation of active site Asp179 to Asn. The mutated enzyme, CH(D179N), has an altered substrate preference, favoring dUMP rather than dCMP [Graves, K. L., et al. (1992) Biochemistry 31, 10315]. A value of 0.8 was determined for the alpha-secondary tritium equilibrium isotope effect on the binding of [6-3H]FdUMP to wild-type CH and to CH(D179N), using a mixture of 2-14C- and 6-3H-labeled FdUMP. These effects, similar to that found for TS, indicate that C6 of the nucleotide is saturated (i.e., sp3 hybridized) in the covalent complex of CH, FDUMP, and CH2THF. This strongly suggests that catalysis by CH proceeds via sequential sp2-->sp3-->sp2 hybridization changes at C6 of substrate nucleotides, and it is consistent with a transient covalent linkage of C6 to the thiol of an essential CH residue, Cys148. The values of the alpha-secondary 3H kinetic isotope effect (KIE) on kcat/KM for CH-catalyzed formation of Hm5dCMP caused by 6-3H-substitution of dCMP, with both wild-type CH and CH(D179N), were very close to 1.0. However, the KIE for CH-(D179N) with dUMP was 0.82.(ABSTRACT TRUNCATED AT 250 WORDS)


Layer-dependent surface potential of phosphorene and anisotropic/layer-dependent charge transfer in phosphorene-gold hybrid systems.
The surface potential and the efficiency of interfacial charge transfer are extremely important for designing future semiconductor devices based on the emerging two-dimensional (2D) phosphorene. Here, we directly measured the strong layer-dependent surface potential of mono- and few-layered phosphorene on gold, which is consistent with the reported theoretical prediction. At the same time, we used an optical way photoluminescence (PL) spectroscopy to probe charge transfer in the phosphorene-gold hybrid system. We firstly observed highly anisotropic and layer-dependent PL quenching in the phosphorene-gold hybrid system, which is attributed to the highly anisotropic/layer-dependent interfacial charge transfer.


Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant.
The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested. Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls. There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024). The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.


Hop Stunt Viroid: Effects on Vegetative Growth and Yield of Hop Cultivars, and Its Distribution in Central Washington State.
Hop stunt viroid (HSVd) is an economically important pathogen that reduces growth and yield of hops. Visual symptoms of infected hop are highly dependent on cultivar. A study was conducted using six cultivars of hop to determine the impact on yield. Average dry cone yields of infected 'Glacier', 'Cascade', and 'Willamette' were reduced by 62, 14, and 34%, respectively, relative to noninoculated healthy plants. No significant yield reduction was observed for 'Nugget', 'Columbus', and 'Galena'. The α-acid and β-acid contents showed a parallel pattern. Horticultural parameters of Willamette and Nugget were measured in the final year of the study. Internode length, shoot length, and side-arm length were reduced by 29, 26, and 73%, respectively, for infected Willamette bines relative to noninfected bines; no effects were observed resulting from infection of Nugget. To understand the current potential impact of HSVd, a survey was conducted to determine its distribution in central Washington. The survey revealed that 17% of hop plants tested are infected. Hop yield and hop plant longevity will be significantly affected by this level of infection. Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .


Genes from a Dietzia sp. for synthesis of C40 and C50 beta-cyclic carotenoids.
Dietzia sp. CQ4 accumulated the C(40) beta-cyclic carotenoids (canthaxanthin and echinenone) and the C(50) beta-cyclic carotenoid (C.p.450 monoglucoside). A plant-type lycopene beta-cyclase gene crtL was identified for beta-cyclization of the C(40) carotenoids. A carotenoid synthesis gene cluster was identified away from the crtL gene, which contained the crtEBI genes for the synthesis of lycopene followed by the lbtABC genes for lycopene elongation and beta-cyclization of the C(50) carotenoids. This C(50) beta-cyclic carotenoid synthesis gene cluster from Dietzia sp. CQ4 showed high homology with the gene clusters for synthesizing the C(50) epsilon-cyclic carotenoids (decaprenoxanthin and glucosides) from Corynebacterium glutamicum and Agromyces mediolanus. One unique feature of the C(50) beta-cyclic carotenoid synthesis genes in Dietzia sp. CQ4 was that the gene encoding a C(50) carotenoid beta-cyclase subunit and the gene encoding the lycopene elongase appeared to be fused as a single gene (lbtBC). Expression of the gene (lbtA) encoding another subunit of the C(50) carotenoid beta-cyclase and the lbtBC gene in lycopene-accumulating Escherichia coli produced almost exclusively the C(50) beta-cyclic carotenoid C.p.450. One gene (crtX) with high homology to glycosyl transferases was transcribed in the opposite orientation downstream of the lbtBC gene. The crtX gene was likely involved in C.p.450 glucosylation in Dietzia sp. CQ4. The pathway analogous to the synthesis of the C(50) epsilon-cyclic carotenoids was proposed for the synthesis of the C(50) beta-cyclic carotenoids.


Hematopoietic stem cell transplantation in children and adolescents with GATA2-related myelodysplastic syndrome.
GATA2 deficiency is a heterogeneous multi-system disorder characterized by a high risk of developing myelodysplastic syndrome (MDS) and myeloid leukemia. We analyzed the outcome of 65 patients reported to the registry of the European Working Group (EWOG) of MDS in childhood carrying a germline GATA2 mutation (GATA2mut) who had undergone hematopoietic stem cell transplantation (HSCT). At 5 years the probability of overall survival and disease-free survival (DFS) was 75% and 70%, respectively. Non-relapse mortality and relapse equally contributed to treatment failure. There was no evidence of increased incidence of graft-versus-host-disease or excessive rates of infections or organ toxicities. Advanced disease and monosomy 7 (-7) were associated with worse outcome. Patients with refractory cytopenia of childhood (RCC) and normal karyotype showed an excellent outcome (DFS 90%) compared to RCC and -7 (DFS 67%). Comparing outcome of GATA2mut with GATA2wt patients, there was no difference in DFS in patients with RCC and normal karyotype. The same was true for patients with -7 across morphological subtypes. We demonstrate that HSCT outcome is independent of GATA2 germline mutations in pediatric MDS suggesting the application of standard MDS algorithms and protocols. Our data support considering HSCT early in the course of GATA2 deficiency in young individuals.


Image guided audit of surgery for temporal lobe epilepsy.
Studies on surgery for temporal lobe epilepsy are hampered by lack of information about the actual surgery that has taken place. A method is described for accurately measuring the volumes of resection by MRI after surgery. Ten cases of surgically treated temporal lobe epilepsy (nine non-tailored resections, one selective amygdalohippocampectomy) are presented to show the technique. Indices of extent of resection in both the mesiobasal and lateral temporal lobe compartments have been measured, compared, and evaluated. By comparison with identical preoperative volumetric MRI the hippocampal resections have been correlated with the demonstrated hippocampal volume loss, thought to be of relevance in the aetiology of temporal lobe epilepsy. Detailed postoperative audit in this manner is vital in providing a rational basis for follow up studies of outcome.


[Epidemiology of resistance to antituberculosis drugs in Mycobacterium tuberculosis complex strains isolated from adenopathies in Djibouti. Prospective study carried out in 1999].
Tuberculosis is a major cause of death in the Republic of Djibouti. Tuberculous lymphadenitis represents about 25% of the clinical forms of tuberculosis in this country. Between January 1999 and April 1999, 196 lymph node specimens were consecutively collected from 153 patients living in Djibouti. Testing of susceptibility to the major anti-tuberculosis drugs was performed by the proportion method. Growth of Mycobacterium tuberculosis complex strains was obtained from specimens of 85 patients including 9 with prior treatment. Strains were identified as Mycobacterium tuberculosis in 78 cases, Mycobacterium canetti in 3, Mycobacterium africanum in 3, and Mycobacterium bovis in 1. Prevalence of HIV infection was 15%. Assessment of primary resistance demonstrated that the overall resistance rate, i.e., resistance to 1 or more drugs, was 18 (21.2%). Results showed resistance to isoniazid (H) in 6 cases (7.1%), rifampicin (R) in 3 (3.5%), ethambutol (E) in 1 (1.2%), streptomycin (S) in 13 (15.3%) and pyrazinamide (Z) in 1 (1.2%). Multidrug resistance (MDR) was found in 2 cases (2.4%). Assessment of acquired resistance demonstrated resistance to H in 4 cases (44%), R in 2 (22%), S in 2 (22%), E in 0, Z in 0 and MDR in 1 (11%). These findings were not significantly different from data obtained from sputum samples analysed between 1997 and 2000 or from those described in a study conducted in 1985.


Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors.
G-protein coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across membranes, and represent major targets in the development of novel drug candidates in all clinical areas. Membrane cholesterol has been reported to have an important role in the function of a number of GPCRs. Several structural features of proteins, believed to result in preferential association with cholesterol, have been recognized. Cholesterol recognition/interaction amino acid consensus (CRAC) sequence represents such a motif. Many proteins that interact with cholesterol have been shown to contain the CRAC motif in their sequence. We report here the presence of CRAC motifs in three representative GPCRs, namely, rhodopsin, the β(2)-adrenergic receptor, and the serotonin(1A) receptor. Interestingly, the function of these GPCRs has been previously shown to be dependent on membrane cholesterol. The presence of CRAC motifs in GPCRs indicates that interaction of cholesterol with GPCRs could be specific in nature. Further analysis shows that CRAC motifs are inherent characteristic features of the serotonin(1A) receptor and are conserved over natural evolution. These results constitute the first report of the presence of CRAC motifs in GPCRs and provide novel insight in the molecular nature of GPCR-cholesterol interaction.


Reducing global risk for cardiovascular disease: using lifestyle changes and pharmacotherapy.
Cardiovascular disease (CVD) is the leading cause of death and disability in industrialized societies, due in large part to the lack of a comprehensive approach to control the risk factors for atherosclerosis. One strategy for reducing an individual's global CVD risk relies on a targeted approach that modifies each of the major independent risk factors prevalent in both symptomatic (secondary prevention) and asymptomatic (primary prevention) patients. These interventions include lipid lowering, smoking cessation, blood pressure control, glycemic control, regular exercise, and the use of various medications. This review offers an evidence-based strategy toward reducing an individual's global risk for CVD by addressing the modifiable, major independent risk factors.


Examining a role for PKG Iα oxidation in the pathogenesis of cardiovascular dysfunction during diet-induced obesity.
Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state. Diet-induced obesity is associated with NOS uncoupling, which may in part contribute to the associated cardiovascular dysfunction due to exacerbated PKG Iα disulfide oxidation to the disulfide state. This is a rational hypothesis because PKG Iα oxidation is known to significantly contribute to heart failure that arises from chronic myocardial oxidative stress. Bovine arterial endothelial cells (BAECs) or smooth muscle cells (SMCs) were exposed to drugs that uncouple NOS. These included 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) which promotes its S-glutathiolation, 4-diamino-6-hydroxy-pyrimidine (DAHP) which inhibits guanosine-5'-triphosphate-cyclohydrolase 2 to prevent BH4 synthesis or methotrexate (MTX) which inhibits the regeneration of BH4 from BH2 by dihydrofolate reductase. While all the drugs mentioned above induced robust PKG Iα disulfide dimerization in cells, exposure of BAECs to NOS inhibitor L-NMMA did not. Increased PKG Iα disulfide formation occurred in hearts and aortae from mice treated in vivo with DAHP (10mM in a drinking water for 3 weeks). Redox-dead C42S PKG Iα knock-in (KI) mice developed less pronounced cardiac posterior wall hypertrophy and did not develop cardiac dysfunction, assessed by echocardiography, compared to the wild-type (WT) mice after chronic DAHP treatment. WT or KI mice were then subjected to a diet-induced obesity protocol by feeding them with a high fat Western-type diet (RM 60% AFE) for 27 weeks, which increased body mass, adiposity, plasma leptin, resistin and glucagon levels comparably in each genotype. Obesity-induced hypertension, assessed by radiotelemetry, was mild and transient in the WT, while the basally hypertensive KI mice were resistant to further increases in blood pressure following high fat feeding. Although the obesogenic diet caused mild cardiac dysfunction in the WT but not the KI mice, gross changes in myocardial structure monitored by echocardiography were not apparent in either genotype. The level of cyclic guanosine monophosphate (cGMP) was decreased in the aortae of WT and KI mice following high fat feeding. PKG Iα oxidation was not evident in the hearts of WT mice fed a high fat diet. Despite robust evidence for PKG Iα oxidation during NOS uncoupling in cell models, it is unlikely that PKG Iα oxidation occurs to a significant extent in vivo during diet-induced obesity and so is unlikely to mediate the associated cardiovascular dysfunction.


Hybridization of MOFs and polymers.
Metal-organic frameworks (MOFs) have received much attention because of their attractive properties. They show great potential applications in many fields. An emerging trend in MOF research is hybridization with flexible materials, which is the subject of this review. Polymers possess a variety of unique attributes, such as softness, thermal and chemical stability, and optoelectrical properties that can be integrated with MOFs to make hybrids with sophisticated architectures. Hybridization of MOFs and polymers is producing new and versatile materials that exhibit peculiar properties hard to realize with the individual components. This review article focuses on the methodology for hybridization of MOFs and polymers, as well as the intriguing functions of hybrid materials.


Gradient tabu search.
This paper presents a modification of the tabu search called gradient tabu search (GTS). It uses analytical gradients for a fast minimization to the next local minimum and analytical diagonal elements of the Hessian to escape local minima. For an efficient blocking of already visited areas tabu regions and tabu directions are introduced into the tabu list (TL). Trials with various well-known test functions indicate that the GTS is a very promising approach to determine local and global minima of differentiable functions. Possible application areas could be optimization routines for force field parameters or conformational searches for large molecules.


Acute myeloid leukemia presenting as spinal cord compression.
We report the findings of a 10-year-old boy who presented to a pediatric emergency department with symptoms of spinal cord compression. Radiological imaging demonstrated multiple soft tissue masses in the head and spine. The surgical pathology showed that the masses were comprised of myeloid leukemia cells. These findings were consistent with those observed on bone marrow aspiration. The characteristics and management of extramedullary leukemia are discussed.


Association of High Serum Adiponectin with the Risk of Malnutrition and Worse Outcome in Head Trauma Patients; a Cohort study.
A number of studies have shown the association between serum adiponectin level and the nutritional status. This study aimed to evaluate the relation between serum adiponectin and changes in nutritional status of head trauma patients. The current prospective cohort study was carried out on head trauma patients who were hospitalized in ICU of a General Teaching Hospital, Sulaimani, Iraq. Patients were divided into two groups based on their serum adiponectin level during the first 24 hours of admission (<15mg/L and ≥15 mg/L) and malnutrition and nutritional indices were compared between groups 1, 6 and 13 days after admission. Sixty-four patients with the mean age of 35.97 ± 11.5 years were studied (59.4% male; 57% traffic accidents). The nutritional status of head trauma patients with serum adiponectin ≥15 mg/L significantly deteriorated from day 1 to 13 based on different nutritional status indices. BMI (p = 0.08), LBM (p = 0.002), APM (p = 0.009), and MUAC (p = 0.008) had a significant decreasing trend from day 1 to day 13 in patients with serum adiponectin level ≥ 15 mg/L. In addition, the number of high risk patients for developing malnutrition based on NUTRIC score (p < 0.001) and the number of severely malnourished cases based on SGA score (p < 0.001) significantly increased from day 1 to 13 in this group. The severity of disease based on APACHE (p < 0.001) and SOFA (p < 0.001) scores increased in the mentioned cases during the follow up period. Serum adiponectin level ≥ 15 is associated with significant deterioration in nutritional status, increase in the risk of malnutrition, and worsening of the clinical outcome in patients with moderate to severe head trauma in ICU.


Modulation of Sustained Attention by Theta-tACS over the Lateral and Medial Frontal Cortices.
Theta oscillations over the posterior medial frontal cortex (pMFC) and lateral prefrontal cortex (LPFC) play vital roles in sustained attention. Specifically, pMFC power and pMFC-LPFC synchronization correlate with cognitive control in sustained-attention-related tasks, but the causal relationships remain unknown. In the present study, we first analyzed the correlation between EEG theta oscillations (characterized by time-frequency power and phase-based connectivity) and the level of sustained attention (Experiment 1) and then utilized transcranial alternating current stimulation (tACS) to modulate theta oscillations and in turn observed its effects on sustained attention (Experiment 2). In Experiment 1, two time-frequency regions of interest (ROIs) were determined, in which high/low time-frequency power and high/low phase-based connectivity corresponded to high/low-level sustained attention. In Experiment 2, time-frequency power and phase-based connectivity of theta oscillations were compared between the sham and tACS groups within the time-frequency ROIs determined in Experiment 1. Results showed that phase-based connectivity between pMFC and LPFC significantly decreased in the tACS group compared with the sham group during the first five minutes of the poststimulation period. Moreover, a marginal trend existed that sustained attention was downregulated by tACS in the same time interval, suggesting that theta phase synchronization between pMFC and LPFC may play a causal role in sustained attention.


Monolithic modulator and demodulator of differential quadrature phase-shift keying signals based on silicon microrings.
Silicon microring resonators are proposed to achieve ultrasmall differential quadrature phase-shift keying modulators and demodulators operated at 20 Gb/s, which may require a dramatically reduced chip size. The modulators are characterized in terms of the carrier transit time and misalignment of the driving signals, while the demodulation performance is analyzed in terms of the bandwidth and frequency detuning of the demodulator. A bit-error rate of <10(-9) is achieved using all microring-based devices in the back-to-back case.


Colitis associated with Clostridium difficile in specific-pathogen-free C3H-scid mice.
Soft feces and a decreased delivery rate were observed in a specific-pathogen-free (SPF) C3H-scid mouse breeding colony. Grossly, the ceca were shrunken and edematous in the affected mice. Histopathologically, severe edema in the cecal submucosa as well as infiltration of inflammatory cells in the lamina propria and submucosa of the ceca and colon were observed. No pathogenic microorganisms were detected by the routine microbiological tests. By anaerobic bacterial-examination, Clostridium (C.) difficile with toxin A was isolated from the cecal contents of the affected mice. The mice were diagnosed with C. difficile-associated colitis. This case appears to be the first report of natural infection with C. difficile in SPF mice with clinical signs.


Flash Points of Secondary Alcohol and n-Alkane Mixtures.
The flash point is one of the most important characteristics used to assess the ignition hazard of mixtures of flammable liquids. To determine the flash points of mixtures of secondary alcohols with n-alkanes, it is necessary to calculate the activity coefficients. In this paper, we use a model that allows us to obtain enthalpy of fusion and enthalpy of vaporization data of the pure components to calculate the liquid-solid equilibrium (LSE) and vapor-liquid equilibrium (VLE). Enthalpy of fusion and enthalpy of vaporization data of secondary alcohols in the literature are limited; thus, the prediction of these characteristics was performed using the method of thermodynamic similarity. Additionally, the empirical models provided the critical temperatures and boiling temperatures of the secondary alcohols. The modeled melting enthalpy and enthalpy of vaporization as well as the calculated LSE and VLE flash points were determined for the secondary alcohol and n-alkane mixtures.


Association of Metabolic Syndrome with Hyper Apolipoprotein B status in Young People with Acute Coronary Syndrome.
Prevalence of Metabolic Syndrome (MetS) and acute coronary syndrome (ACS) in young people is progressively increasing. This was originally a case control study to predict the risk of ACS with hyper apolipoprotein B (Hyper apoB) status in young people, with 50 cases of 18-45 years of age of both sex with first attack of acute coronary syndrome admitted in Coronary care unit of Mymensingh Medical College Hospital from June 2009 to May 2010 and for comparison, equal number of age and sex matched healthy controls were chosen. In present study only cases were analyzed regarding their anthropometric, fasting blood glucose, blood pressure and lipoprotein lipid profiles. Regarding anthropometric measurement, body mass index (BMI), Waist Circumference (WC) and Waist-to Hip ratio (WHR) was calculated. Thirty one cases had increased and 19 had normal WHR, of them 28 cases had hyper and 3 had normal ApoB and 14 cases out of 19 with normal WHR had hyper ApoB and hyper ApoB status was significantly found to be present in ACS patients with increased waist-hip ratio (p=0.03). In this study WHR, instead of WC was used by the author to define abdominal obesity for the diagnosis of MetS along with other criteria according to IDF (International Diabetic Federation) consensus worldwide definition of Mets. Out of 50 young ACS cases 14 cases had metabolic syndrome of those 12 had hyper ApoB status and was statistically significant (p=0.04).


Blunt Trauma Neck with Complete Tracheal Transection - A Diagnostic and Therapeutic Challenge to the Trauma Team.
Survival following trachea-esophageal transection is uncommon. Establishing a secure airway has the highest priority in trauma management. Airway management is a unique and a defining element to the specialty of emergency medicine. There is no doubt regarding the significance of establishing a patent airway in the critically ill patient in the emergency department. Cannot intubate and cannot ventilate situation is a nightmare to all emergency physicians. The most important take-home message from this case report is that every Emergency physician should have the ability to predict "difficult airway" and recognize "failed airway" very early and be skilled in performing rescue techniques when routine oral-tracheal intubation fails. Any delay at any step in the "failed airway" management algorithm may not save the critically ill dying patient. Here, we report a case of blunt trauma following high-velocity road traffic accident, presenting in the peri-arrest state, in whom we noticed "failed airway" which turned out to be due to complete tracheal transection. In our patient, although we had secured the airway immediately, he had already sustained hypoxic brain damage. This scenario emphasizes the importance of prehospital care in developing countries.


Compomers in restorative therapy of children: a literature review.
The restoration of carious primary teeth plays an underestimated role in paediatric dentistry. This is astonishing for many reasons, not least because many new materials have been introduced in recent years. New or modified techniques and materials, with better aesthetics and flexural properties, allow minimally invasive treatment. A transfer of techniques between different dentitions, however, may be problematic because of both micromorphological differences and compliance. Therefore, this paper deals with options for restoring primary teeth and the early stages of the mixed dentition using polyacid-modified composites, the so-called compomers. Medline and Embase were scanned from 1990 through 2006. Furthermore, a hand-search of nonlisted but peer-reviewed papers was performed. The search items were compomer*, dent*, primary* and deciduous*, which identified 109 relevant publications. Based on high clinical success rates, compomers are now an effective alternative to other materials for restorative therapy in the anterior and posterior primary teeth. A minimum amount of compliance is still mandatory in order to allow for a few minutes of adhesive pretreatment and layering without contamination. If this is not the case, compomers make no sense. Stainless steel crowns are still the most effective from of restoration for severely decayed primary molars.


Identification of in vivo phosphorylation sites and their functional significance in the sodium iodide symporter.
The Na+/I- symporter (NIS)-mediated iodide uptake activity is the basis for targeted radioiodide ablation of thyroid cancers. Although it has been shown that NIS protein is phosphorylated, neither the in vivo phosphorylation sites nor their functional significance has been reported. In this study, Ser-43, Thr-49, Ser-227, Thr-577, and Ser-581 were identified as in vivo NIS phosphorylation sites by mass spectrometry. Kinetic analysis of NIS mutants of the corresponding phosphorylated amino acid residue indicated that the velocity of iodide transport of NIS is modulated by the phosphorylation status of Ser-43 and Ser-581. We also found that the phosphorylation status of Thr-577 may be important for NIS protein stability and that the phosphorylation status of Ser-227 is functionally silent. Thr-49 appears to be critical for proper local structure/conformation of NIS because mutation of Thr-49 to alanine, aspartic acid, or serine results in reduced NIS activity without alterations in total or cell surface NIS protein levels. Taken together, we showed that NIS protein levels and functional activity could be modulated by phosphorylation through distinct mechanisms.


Vulvar Langerhans cell histiocytosis: a case report.
Langerhans cell histiocytoses (LCH) are a rare group of disorders that comprise a large spectrum of diseases initially known as histiocytosis X. In this case report, we relate a case of LCH affecting the vulva of a 47-year-old female. The patient presented since 3 years with a vulvar lesion characterized by non-healing ulcers and a perineal granuloma on which she underwent surgery. Professionals should keep in mind not to treat straightforwardly lesions of the genital tract as simple sexually transmitted diseases. Chronic, atypical genital lesions seen in women need to be worked up and dealt with accordingly.


[Immunoadjuvant effect of Hsp70L1 in tumor vaccine].
To explore the immune enhancement of Hsp70L1 in the tumor cell vaccines. TRP2(153-243) and Hsp70L1 genes were obtained by RT-PCR from B16 cells in murine melanoma and from spleens of C57BL/6 mice and then were inserted into pcDNA3.1/V5-His eukaryotic expression vectors respectively. The recombinants of pTRP2, pHSP70L1 or pTRP2-Hsp fusion gene were obtained and transfected into B16 cells respectively. TRP2(153-243), HSP70L1 or TRP2-Hsp fusion gene-expressing B16 cells were then induced to necrosis by freezing-thawing or to apoptosis by mitomycin C. C57BL/6 mice were immunized with the necrotic or apoptotic B16 cells twice, then the live B16 tumor cells were transplanted into the immunized mice and the tumor growth was observed in some tumor-bearing mice. IFN-gamma-producing cells in splenocytes were measured by flow cytometry and the CTL activity of spleno-lymphocyte was detected by LDH release assay. After the normal mice were immunized with the necrotic or apoptotic tumor vaccines modified with TRP2(153-243), Hsp70L1 or TRP2-Hsp fusion genes, CTL lysis activity and IFN-gamma production from the splenic lymphocytes were promoted in the groups of Hsp70L1 and TRP2-Hsp modified tumor vaccines (P<0.05 or P<0.01). Additionally, the tumor growth was inhibited obviously in the groups of mice immunized with necrotic tumor vaccines (P<0.05 or P<0.01). However, no marked inhibition of tumor growth was observed in the groups of mice immunized with apoptotic tumor vaccines (P>0.05). Hsp70L1 remarkably improves the immunogenicity of B16 tumor vaccines, especially that of necrotic tumor vaccines.


Connective tissue of cervical carcinoma xenografts: associations with tumor hypoxia and interstitial fluid pressure and its assessment by DCE-MRI and DW-MRI.
Abstract Background. A high fraction of stroma in malignant tissues is associated with tumor progression, metastasis, and poor prognosis. Possible correlations between the stromal and physiologic microenvironments of tumors and the potential of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in quantification of the stromal microenvironment were investigated in this study. Material and methods. CK-160 cervical carcinoma xenografts were used as preclinical tumor model. A total of 43 tumors were included in the study, and of these tumors, 17 were used to search for correlations between the stromal and physiologic microenvironments, 11 were subjected to DCE-MRI, and 15 were subjected to DW-MRI. DCE-MRI and DW-MRI were carried out at 1.5 T with a clinical MR scanner and a slotted tube resonator transceiver coil constructed for mice. Fraction of connective tissue (CTFCol) and fraction of hypoxic tissue (HFPim) were determined by immunohistochemistry. A Millar SPC 320 catheter was used to measure tumor interstitial fluid pressure (IFP). Results. CTFCol showed a positive correlation to IFP and an inverse correlation to HFPim. The apparent diffusion coefficient assessed by DW-MRI was inversely correlated to CTFCol, whereas no correlation was found between DCE-MRI-derived parameters and CTFCol. Conclusion. DW-MRI is a potentially useful method for characterizing the stromal microenvironment of tumors.


Studies on the cause of hyperuricosuria in cystic fibrosis patients.
Qualitative and quantitative analyses of the purine contents of 24 pancreatic enzyme preparations currently available in the Federal Republic of Germany were carried out; guanine, adenine, and hypoxanthine were demonstrated in all drugs examined. The contamination level per dosage unit ranged from 2 to 10 mg urate equivalents, which, after purine absorption and metabolism, must be excreted by the kidneys. Although the additional daily urate intake through the ingestion of pancreatic enzyme preparations was less than 70 mg in 16 of 18 cystic fibrosis patients, uric acid excretion was astoundingly high. Compared to the amount of urate excreted in the urine over a 24-h period, urate intake through pancreatic enzyme preparations was so low that these drugs do not represent an important contributing factor for hyperuricosuria. A clear-cut relationship could be demonstrated between the urinary urate concentration and the severity of the disease. The increased catabolism of these patients therefore is more likely the real cause of the hyperuricosuria demonstrable in most cases. Increased fluid intake and administration of allopurinol proved to be an extremely effective means of controlling hyperuricosuria; no side effects were observed.


Infrared emission spectroscopy of glow discharge formed in low pressure atmospheric gases.
Laboratory study was conducted on the molecular and atomic emissions which are considered detectable in the IR radiative background of the upper atmosphere. The IR spectra of glow discharge emission formed in air and other atmospheric constituent gases of 0.1-Torr pressure and a 30-m long column were surveyed using the technique of Fourier spectroscopy. Several features hitherto unobserved were detected in our survey study.


Perceived oral health in a diverse sample.
Measures of perceived oral health represent subjective, individual perspective of one's health. One measure commonly used is the single-item perceived oral health rating: How would you rate your overall oral health? These analyses examine the associations among age, ethnicity, and perceived oral health within the context of a comprehensive battery of 21 predisposing, enabling, and need variables. The study of compares the adult data from three United States research locations of the International Collaborative Study of Oral Health Outcomes (ICS-II). Only social survey data were used for this analysis. The multiple regression model explains over 30% of the variance in perceived oral health, with R squares ranging from 0.324 for Indian Health Service sites to 0.391 for San Antonio. The most important significant predictors include ethnic group, education, perceived general health status, being edentulous or not having a partial denture, having no oral pain, fewer oral symptoms, and having one or more dental visits. The predictors of positive perceived oral health for the diverse groups highlight interesting age and ethnic differences. The only universal predictor for the middle-aged adults was having fewer oral symptoms. For the older adults, being edentulous or not having a partial denture was the only universal predictor. The findings suggest that perceived oral health may be a useful outcome measure in dentistry because of its relation to predisposing sociodemographics and dental utilization.


Two-Tension-Band Technique in Revision Surgery for Fixation Failure of Patellar Fractures.
BACKGROUND Failed patellar fracture fixation is rare, and is usually attributed to technical errors. There are no specific details available on how to address this problem. We present our two-tension-band technique for fixing patellar fractures. MATERIAL AND METHODS Between March 2010 and March 2013, 4 men and 2 women with failed fixation patellar fractures were treated in our department. Their average age was 34 years (range 23-49 years). The initial fracture type was C1 in 3, C2 in 1, and C3 in 2, according to the AO classification. The initial fracture patterns included 3 transverse and 3 comminuted fractures. There were no open fractures. All patients underwent internal fixation with a modified anterior tension band (MATB) supplemented with cerclage wiring. All failures were caused by tension bands sliding past the tip of the Kirschner wires. The mean time between the primary and revision operations was 16.2 months (range 2-63 months). We revised the fractures by two-separate-tension-band technique. RESULTS The mean follow-up was 52 months (range 31-67 months). All patients healed radiographically without complications at an average of 14.7 weeks (range 8-20 weeks). The Bostman knee score was excellent in 3 and good in 3. All patients regained full extension and the mean range of flexion was 147.5° (135-155°). CONCLUSIONS Use of this two-tension-band technique can avoid technical errors and provide more secure fixation. We recommend it for both primary and revision surgery of patellar fractures.


Impact of modelled PM2.5, NO2 and O3 annual air concentrations on some causes of mortality in Tuscany municipalities.
In 2014, the European Environment Agency estimated 59 630 premature deaths in Italy attributable to long-term exposure to PM2.5, 17 290 to NO2 and 2900 to O3. The aim of this study was to test an approach for assessing health impact of the above pollutants analyzing possible associations between annual municipal concentrations, estimated by the national dispersion model developed by ENEA, and mortality rates for trachea, bronchus and lung (TBL) cancer, total respiratory diseases (RD) and chronic obstructive pulmonary diseases (COPD). Tuscany was selected as test case. For the 287 municipalities, 2009-13 standardized mortality rates (SMRates) for each cause of death were calculated by the ENEA epidemiological database. The SMRates of municipalities, aggregated on the basis of the 2003 or 2010 estimated pollutant concentration tertiles, were also computed. TBL cancer SMRate in municipalities with 2003 PM2.5 levels >15.2 μg/m3 was significantly higher than the SMRates of the two lowest tertiles and COPD SMRates in the two highest O3 tertiles were significantly higher than that of the lower tertile. No association between PM2.5 or NO2 concentrations and RD and COPD was detected. Approximately 625 TBL cancer deaths attributable to PM2.5 levels above 10 μg/m3 in 2003 were estimated in the region. Smoking habits and deprivation index were homogeneously distributed among municipalities. This methodological approach allowed detecting associations between mortality and specific air pollutants even at levels below the Italian normative limits and could be employed to evaluate the potential health impact of air pollution in areas where direct measures of concentration are unavailable.


Pearls and pitfalls in the diagnosis of hereditary angioedema.
Hereditary angioedema is a very disabling and even life-threatening chronic condition. A timely and proper diagnosis of the condition is critical in disease management. Unfortunately, there is the potential for misdiagnosis when using the current laboratory diagnostic tools. Physicians should understand the limitations of each diagnostic assay and judiciously establish this life-altering diagnosis.


TGF-β improves myocardial function and prevents apoptosis induced by anoxia-reoxygenation, through the reduction of endoplasmic reticulum stress.
Transforming growth factor-β (TGF-β) is known for its role in ventricular remodeling, inflammatory response, cell survival, and apoptosis. However, its role in improving myocardial function in rat hearts subjected to ischemia-reperfusion (I/R) and protecting against apoptosis induced in cardiomyocytes by anoxia-reoxygenation (A/R) has not been elucidated. This study investigated the protective effects and molecular mechanisms of TGF-β on myocardial function and cardiomyocyte apoptosis. We used TUNEL staining, we tested cell viability, and we measured mitochondrial membrane potential and levels of mitochondrial ROS after 6 h of simulated anoxia together with various durations of simulated reoxygenation in H9c2 cells. We further observed the contractile function in rat hearts after they were subjected to 30 min global ischemia and 180 min reperfusion. Pretreatment with TGF-β markedly inhibited apoptosis in H9c2 cells, as evidenced by increased cell viability and decreased numbers of TUNEL-positive cells, maintained mitochondrial membrane potential, and diminished mitochondrial production of reactive oxygen species (ROS). These changes were associated with the inhibition of endoplasmic reticulum (ER) stress-dependent markers of apoptosis (GRP78, CHOP, caspase-12, and JNK), and the modulation of the expression of Bcl2/Bax. Furthermore, TGF-β improved I/R-induced myocardial contractile dysfunction. All of these protective effects were concentration-dependent. Our results show that TGF-β prevents A/R-induced apoptosis of cardiomyocytes and improves myocardial function in rat hearts injured by I/R.


Erythema Gyratum Repens-Like Purpura in a Patient with Sjögren Syndrome.
The etiology of purpura in Sjögren syndrome (SS) includes cryoglobulinemia, hypergammaglobulinemia, and leukocytoclastic vasculitis (LCV). The clinical symptoms of LCV associated with SS comprise palpable or nonpalpable purpura and urticarial vasculitis. Here, we report a case of LCV presenting as erythema gyratum repens (EGR)-like purpura in a 62-year-old woman with rheumatoid arthritis and SS. EGR-like skin lesions, characterized by annular lesions with expanding concentric pattern and coalescing to form a zebra-like pattern or grain of wood pattern, can appear in various autoimmune conditions; however, EGR-like eruption in SS is extremely rare. On the basis of the expansion pattern, we considered that the EGR-like purpura in this case was elicited by urticarial vasculitis accompanied by SS.


Orbital Edelstein Effect as a Condensed-Matter Analog of Solenoids.
We theoretically study current-induced orbital magnetization in a chiral crystal. This phenomenon is an orbital version of the Edelstein effect. We propose an analogy between the current-induced orbital magnetization and an Ampère field in a solenoid in classical electrodynamics. To quantify this effect, we define a dimensionless parameter from the response coefficients relating a current density with an orbital magnetization. This dimensionless parameter can be regarded as a number of turns within a unit cell when the crystal is regarded as a solenoid, and it represents how "chiral" the crystal is. By focusing on the dimensionless parameter, one can design a band structure that realizes the induction of large orbital magnetization. In particular, a Weyl semimetal with all of the Weyl nodes close to the Fermi energy can have a large value for this dimensionless parameter, which can exceed that of a classical solenoid.


Helicobacter pylori eradication in patients with peptic ulcer disease: clinical consequences and financial implications.
We assessed clinical consequences and financial implications of Helicobacter pylori eradication in 175 patients with peptic ulceration, of whom 106 had been free from H. pylori infection for a mean of 3.2 years, while 69 remained infected. We used quarterly questionnaires to examine consumption of ulcer-healing medication and antacids. In the 106 successfully treated patients, gastrointestinal haemorrhage as a complication of peptic ulcer complications during the 344 patient years after eradication (0.003 per patient year) was 18-fold lower than during the 912 patient years before eradication (0.056 per patient year). Of the H. pylori-negative patients, 12-18% used ulcer-healing medication during any one of the three-month periods of the survey, compared with 34-51% of the patients with residual H. pylori infection. The average cost of the ulcer-healing drugs consumed by the H. pylori-negative patients was 30.59 pounds during the 12 months of the survey, compared with 99.05 pounds for H. pylori-positive patients. Consumption of antacids was also lower in the H. pylori-negative group. Successful eradication of H. pylori significantly reduced the annual cost of ulcer-healing drugs consumed by the patients with ulcer disease. Maintenance of ulcer remission following successful eradication of H. pylori also significantly reduced ulcer complications.


Intraspecific variations in dispersal ability of saproxylic beetles in fragmented forest patches.
The extrapolation of metapopulation concepts to saproxylic insects suggests that the occupancy of forest patches and the colonization of ephemeral deadwood substrates are driven by micro-evolutionary processes that are related to adaptive plasticity and intraspecific sex-dependent polymorphism of dispersal traits. We hypothesized that forest fragmentation could favor more mobile individuals within populations, but little empirical data have been published on the potentially sex-biased response of insect populations to habitat availability. We selected 88 fragmented woodlots in two European agricultural landscapes to cover different degrees of spatio-temporal fragmentation, from small, isolated and recently established woodlots to large, inter-connected ancient woodlots. In line with our hypothesis, the average wing loading (WL), used as a proxy for dispersal ability, for each of nine flight-dispersing saproxylic beetle species should be lower in recent, small, isolated woodlots than in ancient, large, inter-connected woodlots, respectively (i.e. ancient vs. recent, small vs. large, isolated vs. connected). Forest patch size did not significantly influence the average dispersal ability of beetle colonizers. However, WL of one-third of the tested species did significantly respond to forest ancientness or connectivity. Significant patterns were sex-biased, probably due to the contrasting role of males and females in species colonization dynamics. WL was lower in recent than in ancient forest plots for Melandrya barbata males, and it was lower in isolated than in connected woodlots for Tetratoma ancora and Phymatodes testaceus males. Contrary to expectations, we did not observe any decrease in polymorphism of dispersal abilities with decreasing woodlot size or increasing isolation. Our findings give support to the usefulness of gender consideration in insect conservation ecology studies.


[Place of the clinic in studying the nature of schizophrenia].
For successful international studies it is necessary to overcome differences in national psychiatry that are conditioned by the existing clinical methods of research. However, this method is necessary for a cognition of the substrate of a disease as it depicts regularities of clinical expressions of a disease. An example of that is given by Jackson who displayed a correlation between the positive and negative symptoms in a psychosis. This concept is considered from the point of view of relations between adaptive reactions of the organism and a breakage (Pavlov, Davidovsky) and in connection with the nozological problems.


Artificial intelligence (AI) in medicine, current applications and future role with special emphasis on its potential and promise in pathology: present and future impact, obstacles including costs and acceptance among pathologists, practical and philosophical considerations. A comprehensive review.
The role of Artificial intelligence (AI) which is defined as the ability of computers to perform tasks that normally require human intelligence is constantly expanding. Medicine was slow to embrace AI. However, the role of AI in medicine is rapidly expanding and promises to revolutionize patient care in the coming years. In addition, it has the ability to democratize high level medical care and make it accessible to all parts of the world. Among specialties of medicine, some like radiology were relatively quick to adopt AI whereas others especially pathology (and surgical pathology in particular) are only just beginning to utilize AI. AI promises to play a major role in accurate diagnosis, prognosis and treatment of cancers. In this paper, the general principles of AI are defined first followed by a detailed discussion of its current role in medicine. In the second half of this comprehensive review, the current and future role of AI in surgical pathology is discussed in detail including an account of the practical difficulties involved and the fear of pathologists of being replaced by computer algorithms. A number of recent studies which demonstrate the usefulness of AI in the practice of surgical pathology are highlighted. AI has the potential to transform the practice of surgical pathology by ensuring rapid and accurate results and enabling pathologists to focus on higher level diagnostic and consultative tasks such as integrating molecular, morphologic and clinical information to make accurate diagnosis in difficult cases, determine prognosis objectively and in this way contribute to personalized care.


Temperature dependence of dimerization and dewetting of large-scale hydrophobes: a molecular dynamics study.
We studied by molecular dynamics simulations the temperature dependence of hydrophobic association and drying transition of large-scale solutes. Similar to the behavior of small solutes, we found the association process to be characterized by a large negative heat capacity change. The origin of this large change in heat capacity is the high fragility of hydrogen bonds between water molecules at the interface with hydrophobic solutes; an increase in temperature breaks more hydrogen bonds at the interface than in the bulk. With increasing temperature, both entropy and enthalpy changes for association strongly decrease, while the change in free energy weakly varies, exhibiting a small minimum at high temperatures. At around T=Ts=360 K, the change in entropy is zero, a behavior similar to the solvation of small nonpolar solutes. Unexpectedly, we find that at Ts, there is still a substantial orientational ordering of the interfacial water molecules relative to the bulk. Nevertheless, at this point, the change in entropy vanishes due to a compensating contribution of translational entropy. Thus, at Ts, there is rotational order and translational disorder of the interfacial water relative to bulk water. In addition, we studied the temperature dependence of the drying-wetting transition. By calculating the contact angle of water on the hydrophobic surface at different temperatures, we compared the critical distance observed in the simulations with the critical distance predicted by macroscopic theory. Although the deviations of the predicted from the observed values are very small (8-23%), there seems to be an increase in the deviations with an increase in temperature. We suggest that these deviations emerge due to increased fluctuations, characterizing finite systems, as the temperature increases.


Climate Influences the Content and Chemical Composition of Foliar Tannins in Green and Senesced Tissues of Quercus rubra.
Environmental stresses not only influence production of plant metabolites but could also modify their resorption during leaf senescence. The production-resorption dynamics of polyphenolic tannins, a class of defense compound whose ecological role extends beyond tissue senescence, could amplify the influence of climate on ecosystem processes. We studied the quantity, chemical composition, and tissue-association of tannins in green and freshly-senesced leaves of Quercus rubra exposed to different temperature (Warming and No Warming) and precipitation treatments (Dry, Ambient, Wet) at the Boston-Area Climate Experiment (BACE) in Massachusetts, USA. Climate influenced not only the quantity of tannins, but also their molecular composition and cell-wall associations. Irrespective of climatic treatments, tannin composition in Q. rubra was dominated by condensed tannins (CTs, proanthocyanidins). When exposed to Dry and Ambient*Warm conditions, Q. rubra produced higher quantities of tannins that were less polymerized. In contrast, under favorable conditions (Wet), tannins were produced in lower quantities, but the CTs were more polymerized. Further, even as the overall tissue tannin content declined, the content of hydrolysable tannins (HTs) increased under Wet treatments. The molecular composition of tannins influenced their content in senesced litter. Compared to the green leaves, the content of HTs decreased in senesced leaves across treatments, whereas the CT content was similar between green and senesced leaves in Wet treatments that produced more polymerized tannins. The content of total tannins in senesced leaves was higher in Warming treatments under both dry and ambient precipitation treatments. Our results suggest that, though climate directly influenced the production of tannins in green tissues (and similar patterns were observed in the senesced tissue), the influence of climate on tannin content of senesced tissue was partly mediated by the effect on the chemical composition of tannins. These different climatic impacts on leaves over the course of a growing season may alter forest dynamics, not only in decomposition and nutrient cycling dynamics, but also in herbivory dynamics.


Lyophilised plasmas for one-stage determination of factor VIII.
Two batches of lyophilized normal pooled HEPES-stabilized plasma according to ZUCKER [11] and LOELIGER [7] were prepared. The F VIII activity established by the activated partial thromboplastin test (APTT-VIII) was identical in both plasmas and amounted to 0.99 U/ml (95% confidence limits 0.87 to 1.17 U/ml). It did not change within 11 months in plasmas according to ZUCKER, and 6 months in those according to LOELIGER (further on not followed). We prepared four batches of lyophilized HERPES-stabilized substrate plasma (severe form of hemophilia A) according to ZUCKER. They were employed for 5 to 13 months in APTT-VIII along with the frozen 3.2% sodium citrate substrate plasmas. The results showed a satisfactory agreement. The lyophilized plasmas did not influence even the dose-response-line. On the ground of these results we consider the reported lyophilized plasmas to be suitable reagents in APTT-VIII technique.


Carbon monoxide poisoning--Weld County, Colorado, 1993.
In March 1993, the Colorado Department of Public Health and Environment (CDPHE) was notified that six family members residing in a home in Weld County had suffered carbon monoxide (CO) poisoning; five of the persons died. An investigation indicated that the source of CO had been a van parked in the garage of the home; the van had been left running, and the exhaust fumes leaked into the home. This report summarizes the investigation of this incident.


Right Ventricle Failure in Sepsis: A Case Report.
Sepsis could produce myocardial depression and typically it affects the left ventricle (LV). Sepsis could also affect right ventricle (RV), in addition to the interdependence with LV. RV pressure may be elevated secondary to pulmonary vasoconstriction, leading to RV dysfunction. Unlike LV, RV is poorly prepared to compensate for acute overload. Aggressive volume replacement may be vital to maintain RV function, but excess hydration can cause RV dilation, decreased LV diastolic filling, and reduced cardiac output. In patients having signs of inadequate cardiac output even after initial volume resuscitation, RV function should be assessed with echocardiogram. If RV dysfunction is noted, then fluid therapy should be guided by CVP measurements. If cardiac output increases with increasing CVP, maintaining higher filling pressures on the right side is indicated. On the other hand, increasing CVP with worsening of the cardiac output could worsen the RV dysfunction. In addition to the fluid management, treatment of other reversible causes like acidosis and hypoxia is also a key.


Mammalian metabolic rates in the hottest fish on earth.
The Magadi tilapia, Alcolapia grahami, a small cichlid fish of Lake Magadi, Kenya lives in one of the most challenging aquatic environments on earth, characterized by very high alkalinity, unusual water chemistry, and extreme O2, ROS, and temperature regimes. In contrast to most fishes which live at temperatures substantially lower than the 36-40 °C of mammals and birds, an isolated population (South West Hot Springs, SWHS) of Magadi tilapia thrives in fast-flowing hotsprings with daytime highs of 43 °C and night-time lows of 32 °C. Another population (Fish Springs Lagoon, FSL) lives in a lagoon with fairly stable daily temperatures (33-36 °C). The upper critical temperatures (Ctmax) of both populations are very high; moreover the SWHS tilapia exhibit the highest Ctmax (45.6 °C) ever recorded for a fish. Routine rates of O2 consumption (MO2) measured on site, together with MO2 and swimming performance at 25, 32, and 39 °C in the laboratory, showed that the SWHS tilapia exhibited the greatest metabolic performance ever recorded in a fish. These rates were in the basal range of a small mammal of comparable size, and were all far higher than in the FSL fish. The SWHS tilapia represents a bellwether organism for global warming.


Immediate breast reconstruction (IBR) with direct, anatomic, extra-projection prosthesis: 102 cases.
There are different methods described until now for immediate breast reconstruction. Despite the use of autologous flaps considered by many authors, implants are considered as an option by others. A prospective study of 102 clinical cases was designed, including a 1-year follow-up in which glands were reconstructed by immediate breast reconstruction (IBR) with direct, extra projection, anatomic prostheses located in a submuscular pocket after a skin-sparing mastectomy. The prosthesis coverage was made by the muscle in its upper two thirds and by using the skin from the mastectomy in its lower third. The cosmetic results obtained were evaluated according to the volume, form, and symmetry achieved using a linear numeric analogical score. This evaluation had an averaged value of 2.79 +/- 0.8 in our scale from poor (0) to excellent result (4). The overall rate of complications was 15.7% of the cases, with seroma being the most frequent. In conclusion, this preliminary study demonstrates that immediate breast reconstruction with a direct, extra projection, anatomic prosthesis is a good alternative. Nevertheless, more long-term studies with a higher number of patients and using an SF-36 for patient satisfaction are needed to confirm these results.


Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test.
Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.


Sex-dependent association between heart rate variability and pulse pressure in haemodialysis patients.
Increased pulse pressure (PP) is associated with increased cardiovascular mortality in haemodialysis (HD) patients. Autonomic imbalance is common in HD patients and predisposes to sudden cardiac death, but its relationship to PP is unknown. We investigated the relationship between cardiac autonomic modulation assessed by heart rate variability (HRV) and PP in HD patients. Continuous electrocardiograms recorded during HD sessions were repeated 5 times at 2-week intervals in stable HD patients. The high-frequency (HF) and low-frequency (LF) components and the LF/HF ratio of HRV were calculated during the first and last hour of the recordings. These values and the corresponding systolic blood pressure (SBP), diastolic blood pressure (DBP) and PP measurements were averaged in repeated recordings of each patient. Seventy-six patients were included in the final analysis (aged 61 ± 15 years, 32% females, 37% diabetics). In male patients, LF/HF correlated inversely with pre- and post-HD PP (r = -0.369, p = 0.007 and r = -0.546, p = 0.000, respectively), positively with pre- and post-HD DBP (r = 0.358, p = 0.009 and r = 0.306, p = 0.028, respectively) and inversely with post-HD SBP (r = -0.350, p = 0.011). In female patients, LF/HF correlated positively with post-HD SBP (r = 0.422, p = 0.040). We observed an association between PP and HRV in male HD patients. Sex differences may be important for cardiac risk assessment.


RTI 113, a 3-phenyltropane analog, produces long-lasting cocaine-like discriminative stimulus effects in rats and squirrel monkeys.
The 3-phenyltropane analog, 3beta-(4-chlorophenyl)tropane-2beta-carboxylic acid phenyl ester hydrochloride (RTI 113), has been shown to decrease cocaine self-administration in rats, squirrel monkeys and rhesus monkeys. Consequently, it has been proposed as a potential agonist pharmacotherapy for cocaine dependence. However, the time course of the discriminative stimulus effects of RTI 113 has not been determined. The present study was designed to compare the time course of the discriminative stimulus effects of RTI 113 with that of cocaine in rats and squirrel monkeys. Tests were conducted using a drug discrimination procedure in which rats and squirrel monkeys were trained to discriminate 10 and 0.3 mg/kg cocaine from saline, respectively. RTI 113 substituted for cocaine in both species. The time course of the discriminative stimulus effects of RTI 113 was approximately five times longer compared to that of cocaine. RTI 113 is a 3-phenyltropane analog that has long acting cocaine-like discriminative stimulus effects in both rats and squirrel monkeys. These results, combined with those indicating that RTI 113 decreases cocaine self-administration, suggest that RTI 113, or analogs of RTI 113, may be useful tools for developing potential agonist therapies for cocaine dependence.


Glycolate pathway in algae.
No glycolate oxidase activity could be detected by manometric, isotopic, or spectrophotometric techniques in cell extracts from 5 strains of algae grown in the light with CO(2). However, NADH:glyoxylate reductase, phosphoglycolate phosphatase and isocitrate dehydrogenase were detected in the cell extracts. The serine formed by Chlorella or Chlamydomonas after 12 seconds of photosynthetic (14)CO(2) fixation contained 70 to 80% of its (14)C in the carboxyl carbon. This distribution of label in serine was similar to that in phosphoglycerate from the same experiment. Thus, in algae serine is probably formed directly from phosphoglycerate. These results differ from those of higher plants which form uniformly labeled serine from glycolate in short time periods when phosphoglycerate is still carboxyl labeled. In glycolate formed by algae in 5 and 10 seconds of (14)CO(2) fixation, C(2) was at least twice as radioactive as C(1). A similar skewed labeling in C(2) and C(3) of 3-phosphoglycerate and serine suggests a common precursor for glycolate and 3-phosphoglycerate. Glycine formed by the algae, however, from the same experiments was uniformly labeled. Manganese deficient Chlorella incorporated only 2% of the total (14)CO(2) fixed in 10 minutes into glycolate, while in normal Chlorella 30% of the total (14)C was found in glycolate. Manganese deficient Chlorella also accumulated more (14)C in glycine and serine.Glycolate excretion by Chlorella was maximal in 10 mm bicarbonate and occurred only in the light, and was not influenced by the addition of glycolate. No time dependent uptake of significant amounts of either glycolate or phosphoglycolate was observed. When small amounts of glycolate-2-(14)C were fed to Chlorella or Scenedesmus, only 2 to 3% was metabolized after 30 to 60 minutes. The algae were not capable of significant glycolate metabolism as is the higher plant. The failure to detect glycolate oxidase, the low level glycolate-(14)C metabolism, and the formation of serine from phosphoglycerate rather than from glycolate are consistent with the concept of an incomplete glycolate pathway in algae.


The Accuracy of Early Reproductive History and Physical Activity Participation Recall Across Multiple Age Ranges.
Background: The ability to accurately recall specific reproductive health events is an integral aspect of medical decision making and evaluating a female's overall health and wellness across their lifespan. The Health and Reproductive Survey (HeRS) was developed to recall reproductive events and environmental influences on reproductive characteristics throughout the lifespan of a female. This study aimed to determine how reliably women recall certain events during menarche and early reproductive years. It was hypothesized that age at menarche, hormonal contraceptive use, and physical activity would be recalled reliably among all age ranges, while the recall reliability for cycle regularity and length would be more inconsistent with advancing age. Materials and Methods: A total of 144 participants (age: 32.73 ± 11.92), completed the HeRS on two occasions spaced 4 months apart to investigate recall reliability. Cohen's kappa coefficient was used to assess the consistency of categorical responses and 95% limits of agreement were used for continuous data. Results: Although physical activity changes had greater variability than anticipated (0.79), the recall reliability among the youngest (1) and oldest (0.89) age groups was high, and females were able to consistently recall the age of menarche (0.83), physical activity level (0.9), cessation of period during early reproductive years (0.91), and birth control use following menarche (0.85) and during the early reproductive years (0.9). Conclusions: The HeRS is a useful tool for reliably recalling reproductive history and physical activity participation across multiple age ranges and can be utilized to gather crucial information throughout the reproductive lifespan.


Intersections of poverty, race/ethnicity, and sex: alcohol consumption and adverse outcomes in the United States.
We examine whether intersectionality theory-which formalizes the notion that adverse health outcomes owing to having a marginalized social status, identity, or characteristic, may be magnified for individuals with an additional marginalized social status, identity, or characteristic-can be applied using quantitative methods to describe the differential effects of poverty on alcohol consumption across sex and race/ethnicity. Using the National Epidemiologic Survey on Alcohol and Related Conditions, we analyze longitudinal data from Black, Hispanic, and White drinkers (n = 21,140) to assess multiplicative interactions between poverty, as defined by the US Census Bureau, sex, and race/ethnicity, on adverse alcohol outcomes. Findings indicated that the effect of poverty on the past-year incidence of heavy episodic drinking was stronger among Black men and Black women in comparison to men and women of other racial/ethnic groups. Poverty reduction programs that are culturally informed may help reduce racial/ethnic disparities in the adverse outcomes of alcohol consumption.


Transperitoneal versus retroperitoneal laparoscopic partial nephrectomy: initial experience.
We present the transperitoneal and retroperitoneal approaches to laparoscopic partial nephrectomy and compare the outcomes of each technique. Between December 2006 and March 2010, retroperitoneal laparoscopic partial nephrectomy (RLPN) was performed in 23 patients and transperitoneal laparoscopic partial nephrectomy (TLPN) in 26 patients. They were compared regarding surgical technique, operative parameters, postoperative recovery and follow-up data. The 2 approaches used similar operative techniques to control parenchymal bleeding. The patient demographics were similar in both groups. The mean tumour size was 3.1 cm in the retroperitoneal group and 3.4 cm in the transperitoneal group. The difference was not statistically significant (p: 0.095). The mean operative time was significantly longer in the transperitoneal group (215 vs 185 minutes, p: 0.031). The mean warm ischemia time difference was not statistically significant (25 vs 28 minutes, p: 0.102). The mean estimated blood loss (EBL) was greater in the transperitoneal group (254 vs 204 cc, p: 0.003). Moreover, the mean hospital stay was 4.1 days in the RLPN and 4.3 days in the TLPN group (p: 0.303) The difference was not statistically significant. The median follow-up was 11 months (range: 2 to 35) in the retroperitoneal group and 13 months (range 1 to 36) in the transperitoneal group. Our experience has shown that laparoscopic partial nephrectomy is a safe, feasible technique for patients with small exophytic renal tumours. We believe that the decision regarding the approach should be based on the tumor location on the kidney surface.


[Small interfering RNA-mediated monocarboxylate transporter 1 silencing enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis].
To investigate the effect of small interfering RNA (siRNA)-mediated silencing of monocarboxylate transporter 1 (MCT1) on the sensitivity of drug-resistant nasopharyngeal carcinoma HNE1/DDP cells to cisplatin (DDP)-induced apoptosis and explore the possible mechanism. The expression of MCT1 was analyzed in HNE1 and HNE1/DDP cells and in HNE1/DDP cells transfected with siRNA using Western blot. MTT assay was used to assess the inhibitory effect of different concentrations of DDP alone or in combination with MCT1 siRNA on the proliferation of HNE1/DDP cells. The apoptosis of cells treated with MCT1 siRNA or/and DDP (8 µmol/L) was assessed using flow cytometry with PI staining, and the mitochondrial membrane potential was detected using JC-1 staining assay; the expressions of Mcl-1, Bak, Bcl-2, and Bax were analyzed using Western blotting. HNE1/DDP cells showed a high expression of MCT1, and MCT1 silencing using siRNA significantly increased the sensitivity of HNE1/DDP cells to DDP (P<0.05) and partly reversed DDP resistance of the cells. MCT1 silencing enhanced the sensitivity of HNE1/DDP cells to DDP-induced apoptosis. Treatment of HNE1/DDP cells with MCT1 siRNA combined with 8 µmol/L DDP for 24 h resulted in an apoptotic rate of (51.23∓2.86)%, significantly higher than that in cells treated with MCT1 siRNA or DDP alone (P<0.05). The combined treatment also reduced the mitochondrial membrane potential, down-regulated the expression of Mcl-1 and Bcl-2, and up-regulated the expression of Bax in the DDP-resistant cells. MCT1 siRNA can enhance the sensitivity of HNE1/DDP cells to DDP-induced apoptosis, the mechanism of which may involve the down-regulation of Mcl-1 and Bcl-2 and up-regulation of Bax expression.


Accounting for heterogeneity in meta-analysis using a multiplicative model-an empirical study.
In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright © 2016 John Wiley & Sons, Ltd.


Epidural chloroprocaine bolus in emergency cesarean section-lessons learned from a near mishap.
Administration of a large bolus of epidural chloroprocaine to hasten the spread of anesthesia is an accepted practice during emergency cesarean section. Occasionally, this practice can result in a very high block that can compromise patient's safety. We describe a case of epidural chloroprocaine administration in a 4 point position resulting in a high dermatomal block requiring respiratory assistance. Events surrounding the case are discussed, with a view to warn the reader about the pitfalls of such a practice.


[Protein glycosylation in the spores of the microsporidia Paranosema (Antonospora) grylli].
Long adaptation of microsporidia, a large group of fungi-related protozoa, to intracellular lifestyle has resulted in drastic minimization of a parasite cell. Thus, diversity of carbohydrates in microsporidia glycoproteins and proteoglycans is expected to be restricted by O-linked manno-oligosaccharides because three genes involved in O-mannosylation of proteins and no components of N-linked glycosylation machinery were found in genome of human pathogen Encephalitozoon cuniculi. In this study we investigated glycosylation of spore proteins of microsporidia Paranosema (Antonospora) grylli infecting crickets Gryllus bimaculatus. Using periodic acid-Shiff reagent staining we have demonstrated that some P. grylli spore proteins are highly-glycosylated. The major polar tube protein (PTP1) of 56 kDa was shown as the most intensively decorated band. The experiments with N-glycosidase F and WGA lectin did not reveal any N-glycosylated proteins in P. grylli spores. At the same time, incubation of major spore wall protein of 40 kDa (p40) with mannose specific lectin GNA resulted in specific binding that was reduced by pretreatment of the protein with mannosidases. Interestingly, in spite of PTP1 glycosylation, polar tube proteins extracted from P. grylli spores were not precipitated by GNA-agarose. Since P. grylli and E. cuniculi are distantly related, our data suggest that dramatic reduction of protein glycosylation machinery is a common feature of microsporidia.


Topology maps of bond descriptors based on the kinetic energy density and the essence of chemical bonding.
Analysis of the kinetic energy density within a molecule identifies patterns in its electronic structure that are intuitively linked to familiar concepts of chemical bonding. The function ν(r), termed localized-orbital locator and based on the positive-definite kinetic energy density τ+, is employed to characterize classes of covalent bonds in terms of its full topology of all critical points of rank three. Not only does ν(r) reveal patterns in chemical bonding, it also discloses features and the influence of extended electronic cores. Gradient paths define the extension of the valence space around an atomic centre; they separate various core level regions from bonding domains, and partition molecules in sensible bonded subunits. Location and ν(r)-values of critical points add a quantitative aspect to the bond characterization; profiles of unconventional chemical linkages such as charge-shift bonds emerge in a natural way.


[Effects of Tiaoxin and Zishen prescription on hippocampus neurotransmitters in Alzheimer's disease rats].
A method of stereotaxic apparatus was employed to damage the nucleus basalis of Meynert, and the effects of Tiao-xinzishen prescriptions on neurotransmitters such as ACh, 5-HT and NE in hippocampus were observed. Rats were placed on the brain stereotaxic apparatus and received a bilateral lesion of Meynert by IA injection, according to the atlas of Daxinos and Watson. After seven days of lesion, AD rats were selected. Rats were treated with Tiaoxin or/and Zishen prescription for 20 days, respectively. Hippocampus ACh was measured by spectrophotometer and 5-HT and NE by high performance liquid chromatography (HPLC). The contents of hippocampus ACh, 5-HT and NE of AD rats were significantly increased after the treatment with the three prescriptions, respectively. These prescriptions had some up regulating effects on hippocampus neurotransmitters in rats, which had already decreased due to dementia.


Functional platelet-activating factor receptors linked to inositol lipid hydrolysis, calcium mobilization and tyrosine kinase activity in the human endometrial HEC-1B cell line.
Platelet-activating factor (PAF; sn-1-O-alkyl-2-acetyl-sn-glycero-3- phosphocholine) is thought to be an important mediator of embryo-endometrial interactions in early pregnancy, and an understanding of its role in the establishment of early human pregnancy can only follow an understanding of its mechanism of action. In a human endometrial epithelial cell line, HEC-1B, the presence of mRNA encoding the platelet-activating factor receptor was demonstrated by reverse transcription-polymerase chain reaction. The presence of functional receptors was shown by inositol trisphosphate accumulation and a rise in the concentration of intracellular free calcium evoked by platelet-activating factor in myo-[2-3H]inositol-labelled and fura-2-loaded cells, respectively. Platelet-activating factor evoked rapid and concentration-dependent increases in the concentration of intracellular free calcium and inositol trisphosphate that were inhibited by the platelet-activating factor receptor antagonist WEB 2086, indicating that the responses are receptor mediated. Inositol trisphosphate accumulation evoked by platelet-activating factor was unaffected by pretreatment with pertussis toxin. Platelet-activating factor also stimulated the tyrosine phosphorylation of at least two major proteins of 80 kDa and 44 kDa; the smaller protein is an isoform of mitogen-activated protein kinase. These results show that functional platelet-activating factor receptors are located on the endometrial epithelial cell line HEC-1B and are linked to inositol lipid hydrolysis, calcium mobilization and tyrosine kinase activity.


INTRAVENOUS REGIONAL ANTIBIOTIC PERFUSION THERAPY AS AN ADJUNCTIVE TREATMENT FOR DIGITAL LESIONS IN SEABIRDS.
Foot infections are a common problem among seabirds in wildlife rehabilitation. Pododermatitis and digital infections are often challenging to treat because of the presence of suboptimal substrates, abnormal weight-bearing due to injuries, and suboptimal nutritional or health status. Seabirds represent the majority of animals requiring rehabilitation after oil spills, and foot problems are a common reason for euthanasia among these birds. Antibiotic intravenous regional perfusion therapy is frequently used in humans and other species to treat infections of the distal extremities, but it has not been evaluated in seabirds. During the 2015 Refugio oil spill response, four birds with foot lesions (pododermatitis, osteomyelitis, or both) were treated with ampicillin/sulbactam administered intravenously to the affected limb(s) in addition to systemic antibiotics and anti-inflammatories. Three of the birds, all brown pelicans ( Pelecanus occidentalis ) recovered rapidly and were released. Two of these birds had acute pododermatitis and were treated once with intravenous regional perfusion. They were released approximately 3 wk after the perfusion therapy. The third pelican had osteomyelitis of a digit. It was treated twice with intravenous regional perfusion and was released about 1 mo after the initial perfusion therapy. The fourth bird, a Pacific loon ( Gavia pacifica ), was treated once with perfusion therapy but did not respond to treatment and was euthanatized. No serious adverse effects were observed. This technique should be explored further in avian species.


[Characteristics of operational performance and membrane fouling in a sidestream membrane sequencing batch reactor with aerobic granule].
The characteristics of operational performance and membrane fouling were investigated using synthetic wastewater as feed in a sidestream membrane sequencing batch reactor (MSBR) system. The experimental results showed that the average removal efficiencies of COD, TN, TP and NH4+ -N were 90%, 60%-80%, 80% and 95% respectively under the influent COD of 200 mg x L(-1) to 1200 mg x L(-1) during more than 150 days' operation. It was possible to achieve a complete granulation of sludge. In 70th day, sludge particles around 350 microm were detected more than 90%. From then, sludge grew up continuously and finally reached to 394 microm in diameter. With the formation of granular sludge in MSBR, the cleaning time of membrane system was prolonged to 65 days, which was larger than three times compared with flocculent sludge MSBR. It was also much better than conventional MBR. These results clearly demonstrated that the formation of granular sludge was good for improving the resistance to organic loading shock and retaining the membrane fouling of the system, and maintaining the stable operation for a long time.