Biomass and Cordycepin Production by the Medicinal Mushroom Cordyceps militaris-A Review of Various Aspects and Recent Trends towards the Exploitation of a Valuable Fungus.
Cordyceps militaris is an entomopathogenic ascomycete with similar pharmacological importance to that of the wild caterpillar fungus Ophiocordyceps sinensis. C. militaris has attracted significant research and commercial interest due to its content in bioactive compounds beneficial to human health and the relative ease of cultivation under laboratory conditions. However, room for improvement exists in the commercial-scale cultivation of C. militaris and concerns issues principally related to appropriate strain selection, genetic degeneration of cultures, and substrate optimization. In particular, culture degeneration-usually expressed by abnormal fruit body formation and reduced sporulation-results in important economic losses and is holding back investors and potential growers (mainly in Western countries) from further developing this highly promising sector. In the present review, the main factors that influence the generation of biomass and metabolites (with emphasis on cordycepin biosynthesis) by C. militaris are presented and evaluated in conjunction with the use of a wide range of supplements or additives towards the enhancement of fungal productivity in large-scale cultivation processes. Moreover, physiological and genetic factors that increase or reduce the manifestation of strain degeneration in C. militaris are outlined. Finally, methodologies for developing protocols to be used in C. militaris functional biology studies are discussed.


Experimental murine leishmaniasis and the Th1/Th2 cell concept.
Herein, the current knowledge about the immune response during murine cutaneous leishmaniasis is summarized. Special regard is given to the characteristics and generation of Th1 and Th2 cells during this disease. Originally established on the basis of different cytokines produced by T cell clones, it is now known that the Th1/Th2 concept really defines totally different immune pathways that affect most, if not all cells of the immune system. Murine experimental leishmaniasis was the first model to confirm the relevance of the Th1/Th2 concept in vivo. In particular, data from this laboratory will be presented on the role of different IL-4 receptor allotypes, on the role of the transcription factor interferon-regulatory-factor-1 (IRF-1) and the importance of the enzyme inducible NO synthase (iNOS). This work was supported by the SFB 263 and the Fonds der Chemischen Industrie.


Late stomal complications.
Ostomy creation is a common surgical procedure performed by a variety of surgical specialties. Complications associated with stomas are frequent and run the gamut from technical, mechanical, physiologic, and psychologic. The impact of these complications ranges from simple inconvenience to life threatening. The majority of these complications may not occur for years following creation of the stoma. In this article, the author reviews many of the late complications associated with stomas and options regarding their management.


Pharmacokinetics of paracetamol in adults after cardiac surgery.
The pharmacokinetics of paracetamol in adults after cardiac surgery have not been described. Twenty patients were randomized to receive either paracetamol 2 g through a nasogastric tube and as a suppository eight hours later or vice versa. Arterial blood samples were taken at 0.5, one, two, four, six and eight hours after dosing. Each patient was studied for 16 h. There were 16 males and three females. One patient was excluded because of sampling errors. The mean age was 59 (SD 8) years and the mean weight 84 kg (16). The time-concentration profiles for each individual were used to estimate pharmacokinetic parameters using a non-linear mixed effects model (NONMEM). Population parameter estimates with coefficient of variation (CV%), standardized to a 70 kg person, for a one-compartment model with first order input, lag time and first order elimination were volume of distribution 127l (28) and clearance 26.4 l/h (29) Rectal paracetamol had an absorption half-life (Tabs) of 2.02 h (31) with a lag time of 0.28 h. The absorption half-life for the oral preparation was 1.49 h (81) with a lag time of 0.17 h. The relative bioavailability of the rectal compared to the oral formulation was 0.98 (18). Concentrations after either nasogastric or rectal paracetamol 2 g were below a target concentration of 10 mg/l, which is associated with analgesia. Absorption after nasogastric administration was slow compared to healthy adults (Tabs 0.06 to 0.7 h) and the bioavailability was half that expected, due to nasogastric loss. Parameter estimates had large variability. Paracetamol is unlikely to have useful clinical impact in the majority of patients when standard doses (6 g/day) are given on day 1 after cardiac surgery.


Ultrasonic anechoic chamber qualification: accounting for atmospheric absorption and transducer directivity.
Qualifying an anechoic chamber for frequencies that extend into the ultrasonic range is necessary for research work involving airborne ultrasonic sound. The ANSI S12.55/ISO 3745 standard which covers anechoic chamber qualification does not extend into the ultrasonic frequency range, nor have issues pertinent to this frequency range been fully discussed in the literature. An increasing number of technologies employ ultrasound; hence the need for an ultrasonic anechoic chamber. This paper will specifically discuss the need to account for atmospheric absorption and issues pertaining to source transducer directivity by presenting some results for qualification of a chamber at Brigham Young University.


Autonomous progesterone secretion from the bovine corpus luteum in vitro.
While the regulation of progesterone secretion from the corpus luteum by LH has been convincingly demonstrated, the secretory patterns in the absence of any pituitary LH inputs are yet unclear. Consequently, we investigated the progesterone secretion by an in vitro perifusion system to characterize spontaneous progesterone release from the isolated bovine corpus luteum. Slices (120 mg) of midluteal corpora lutea were placed in perifusion chambers and continuously perifused by Medium-199 for 160-320 min. Progesterone was determined by radioimmunoassay in the effluent fractions collected at 2-min intervals. The spontaneous progesterone release from all bovine corpora lutea was pulsatile. Pulses were observed at mean (+/- SEM) intervals of 17.7 +/- 1.5 min with amplitudes of 6.7 +/- 0.5 ng and release rates of 29.5 +/- 2.4 ng.ml-1.(2 min)-1 (N = 5). Addition of 6.7 nmol/l hCG to the perifusion medium appeared to increase the pulse amplitudes and release rates (195 +/- 25% over unstimulated conditions), but did not change the pulse frequencies (N = 3). Perifusions with calcium-free medium containing 50 mumol/l verapamil and 20 mmol/l EGTA tended to suppress the pulse frequencies and amplitudes of this spontaneous progesterone release, whereas addition of hCG reversed this decrease again (N = 3). When prostaglandin activity was inhibited by 100 mumol/l indomethacin added to the perifusion medium, both pulse frequencies and amplitudes of this progesterone release were enhanced (N = 4). During perifusions with 100 mumol/l of the anti-progesterone ZK 96.734, both the pulse frequencies and amplitudes increased (N = 4). These studies demonstrate an episodic progesterone release from the bovine corpus luteum perifused in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)


The work of the Human Proteome Organisation's Proteomics Standards Initiative (HUPO PSI).
This article describes the origins, working practices and various development projects of the HUman Proteome Organisation's Proteomics Standards Initiative (HUPO PSI), specifically, our work on reporting requirements, data exchange formats and controlled vocabulary terms. We also offer our view of the two functional genomics projects in which the PSI plays a role (FuGE and FuGO), discussing their impact on our process and laying out the benefits we see as accruing, both to the PSI and to biomedical science as a whole as a result of their widespread acceptance.


Follow-up after a six-month maintenance period on naltrexone versus placebo in heroin addicts.
Naltrexone and placebo as adjuvant treatment of opioid dependence were compared in a double-blind, controlled clinical trial in 50 heroin addicts. The overall efficacy was assessed by the degree of treatment acceptance, percentage of relapse in heroin consumption, presence of side effects, and overall retention on naltrexone. A total of 50 patients of both sexes, aged from 18 to 30 years, who fulfilled DSM-III-R criteria for opioid dependence were included in the study. All patients completed detoxification with clonidine on an inpatient basis for 2 weeks and subsequently, on an out-patient basis, received oral naltrexone (350 mg per week) for a month. At the beginning of the second month patients were randomly allocated to treatment with naltrexone (28 patients) or placebo (22 patients) until a 6-month treatment period in a double-blind fashion had been completed. During the study period (1 year) all patients followed the same therapeutic schedule. Patients in both groups were comparable in terms of socio-demographic data and toxicological history. The efficacy of naltrexone was not superior to that of placebo as there were no significant differences in acceptance of treatment, retention rates, opioid and other drug consumption, drug compliance or side effects.


Influenza A virus infection and cardiac arrhythmia during the neonatal period.
Influenza virus infection during pregnancy increases the risk of spontaneous abortion, preterm contractions, fetal compromise and early neonatal mortality. We describe a case of fetal and neonatal cardiac arrhythmia coinciding with an influenza A virus infection. Viral RNA was detected in the neonate's nasopharyngeal secretions and also in its serum, indicating influenza viremia. The cardiac arrhythmia resolved spontaneously without antiarrhythmic treatment.


The emerging therapeutic role of antibody mixtures.
A body of evidence suggests that a mixture of therapeutic monoclonal antibodies (mAbs) may be better than a single antibody. Several strategies have been developed to achieve multiple targeting, including the administration of two or more mAbs to the patient, bispecific antibodies and antibody mixtures. Recently, new antibody technologies based on a diverse array of antibodies binding to several different epitopes on any given antigen or antigens have been developed. One of the most promising is the Sympress™ manufacturing technology, which allows the production of an antibody mixture in just one bioreactor as a single drug substance. Recombinant antibody mixtures may be applicable to therapy of neoplastic, autoimmune and infectious diseases.


Acute brain injuries trigger microglia as an additional source of the proteoglycan NG2.
NG2 is a type I transmembrane glycoprotein known as chondroitin sulfate proteoglycan 4 (CSPG4). In the healthy central nervous system, NG2 is exclusively expressed by oligodendrocyte progenitor cells and by vasculature pericytes. A large body of immunohistochemical studies showed that under pathological conditions such as acute brain injuries and experimental autoimmune encephalomyelitis (EAE), a number of activated microglia were NG2 immuno-positive, suggesting NG2 expression in these cells. Alternative explanations for the microglial NG2 labeling consider the biochemical properties of NG2 or the phagocytic activity of activated microglia. Reportedly, the transmembrane NG2 proteoglycan can be cleaved by a variety of proteases to deposit the NG2 ectodomain into the extracellular matrix. The ectodomain, however, could also stick to the microglial surface. Since microglia are phagocytic cells engulfing debris of dying cells, it is difficult to identify a genuine expression of NG2. Recent studies showing (1) pericytes giving rise to microglial after stroke, and (2) immune cells of NG2-EYFP knock-in mice lacking NG2 expression in an EAE model generated doubts for the de novo expression of NG2 in microglia after acute brain injuries. In the current study, we took advantage of three knock-in mouse lines (NG2-CreERT2, CX3CR1-EGFP and NG2-EYFP) to study NG2 expression indicated by transgenic fluorescent proteins in microglia after tMCAO (transient middle cerebral artery occlusion) or cortical stab wound injury (SWI). We provide strong evidence that NG2-expressing cells, including OPCs and pericytes, did not differentiate into microglia after acute brain injuries, whereas activated microglia did express NG2 in a disease-dependent manner. A subset of microglia continuously activated the NG2 gene at least within the first week after tMCAO, whereas within 3 days after SWI a limited number of microglia at the lesion site transiently expressed NG2. Immunohistochemical studies demonstrated that these microglia with NG2 gene activity also synthesized the NG2 protein, suggesting activated microglia as an additional source of the NG2 proteoglycan after acute brain injuries.


Acetazolamide and CO2: acute effects on cerebral and retrobulbar hemodynamics.
Acetazolamide and CO2 are cerebral vasodilators whose specific effects in various brain regions have not been carefully defined. We investigated the effects of these agents in both larger cerebral and smaller, retrobulbar arteries, to compare their general cerebral vasodilatory influence with their specific ocular vascular effects. Twelve young adults with healthy eyes were studied under normocapnic and hypercapnic (6% CO2, 94% O2 tanked gas) conditions after receiving either placebo or 1,000 mg acetazolamide (3 h before study). Color Doppler imaging was used to measure peak systolic and end-diastolic velocities (PSV and EDV) in the internal carotid, middle cerebral, ophthalmic, and central retinal arteries under each condition. Acetazolamide and CO2 each lowered intraocular pressure; combining the agents provided no additive ocular hypotensive effect. Hypercapnia or acetazolamide per se failed to alter PSV, EDV, or the derived resistance index [RI; (PSV-EDV)/PSV] in the internal carotid or in either orbital artery. However, when hypercapnia was superimposed upon acetazolamide, the resistance index fell in the internal carotid and central retinal arteries (each p < 0.05). In contrast, the middle cerebral artery was responsive to either vasodilator and to their combination: PSV and EDV rose, and RI fell with each experimental treatment. In the brain, the middle cerebral artery exhibits substantial dependence of flow velocity on the vasodilators CO2 and acetazolamide. In contrast, the ophthalmic and central retinal arteries appear less responsive. Nonetheless, the combination of carbonic anhydrase inhibition (acetazolamide) with CO2 augmentation did lower vascular resistance distal to the central retinal artery, suggesting that this mechanism vasodilates critical ocular tissues.


Effect of a training course on the diagnosis of vocal fold leukoplakia by narrow-band imaging.
To investigate the value of narrow-band imaging training for differentiating between benign and malignant vocal fold leukoplakia. Thirty cases of vocal fold leukoplakia were selected. Narrow-band imaging endoscopy training had a significant positive effect on the specificity of the differential diagnosis of vocal fold leukoplakia. In addition, the consistency of diagnostic typing of vocal fold leukoplakia by narrow-band imaging improved to 'moderate agreement' following the combination of types I and II and the combination of types IV, V and VI in the typing of vocal fold leukoplakia. The narrow-band imaging training course may improve the ability of laryngologists to diagnose vocal fold leukoplakia. The new endoscopic diagnostic classification by narrow-band imaging needs to be further simplified to facilitate clinical application.


In vitro antioxidant, antimicrobial, cytotoxic potential of gold and silver nanoparticles prepared using Embelia ribes.
In recent years, the green synthesis of gold (GNPs) and silver (SNPs) nanoparticles has gained great interest among chemists and researchers. The present study reports an eco-friendly, cost-effective, rapid and easy method for the synthesis of gold and silver nanoparticles using the seed extract of Embelia ribes (SEEr) as capping and reducing agent. The synthesised GNPs and SNPs were characterised using the following techniques: UV-vis spectroscopy, DLS, HR-TEM, FT-IR and XRD. The free radical scavenging potential of GNPs and SNPs was measured by DPPH assay and Phosphomolybdenum assay. Further, the antimicrobial activity against two micro-organisms were tested using disc diffusion method and cytotoxicity of GNPs and SNPs was determined against MCF-7 cell lines at different concentrations by MTT assay. Both the GNPs and SNPs prepared from E. ribes comparatively showed promising results thereby proving their clinical importance.


Chiral Ligand-Driven Systematic Synthesis of Coordination Polymers with Non-centrosymmetric Structures.
Chirality is an important concept in chemistry revealing intriguing optical properties such as circular dichroism (CD), circularly polarized luminescence (CPL), etc. As one of the non-centrosymmetric (NCS) classes, chiral materials with extended structures may exhibit unique nonlinear optical (NLO) properties, such as second-harmonic generation (SHG). In this Concept article, a series of recently discovered NCS coordination polymers (CPs) from use of carefully designed chiral organic ligands are reviewed. Combining several metal cations such as lanthanides, lead, zinc, and cadmium with rigid chiral ligands has resulted in interesting CPs with both polar and nonpolar structures. Detailed structures, SHG properties, and structure-property relationships are provided. The importance of hyperpolarizability formed by intermolecular hydrogen boding interactions to SHG is emphasized.


Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma.
In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial. Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed. In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8-126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05). Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.


Repression of integrin beta 1 subunit expression by antisense RNA.
A quail cell line (QT6-c) was co-transfected with pTEX vector expressing RNA complementary to chicken integrin beta 1 subunit mRNA (Anti-Int) and pRSVneo vector by a calcium phosphate method. Transfectants showing reduced expression of quail integrin beta 1 subunit were selected with an immunoblot assay, and a few positive clones were examined in detail. Northern blot and immunoblot analyses revealed that the Anti-Int caused a clear reduction of the transcript encoding integrin beta 1 subunit depending on culture conditions. The number of cell surface integrins also decreased in proportion to the decrement of the total amount of integrin beta 1 subunits. When one transfectant (QA23) was cultured in a serum-free medium, cell shape changed from fibroblast-like to neuron-like morphology accompanied by a low growth rate, and the cells did not form focal contact on fibronectin. A similar morphological change occurred in QT6-c cells when the cells were infected with Rous Sarcoma virus, which could produce the Anti-Int. The QA23 cells did not attach to fibronectin as efficiently as did the original QT6-c cells. These data suggest that reduced expression of integrin beta 1 subunit affects cell growth as well as cell morphology by disordering the interaction between integrins and matrix proteins and/or cytoplasmic proteins.


Ovarian hyperstimulation syndrome: an endocrinopathy?
Ovarian hyperstimulation syndrome remains a significant but incompletely understood complication of ovarian stimulation. Evidence has accumulated regarding a role for various cytokines, in particular vascular endothelial growth factor, in its occurrence. However, the pathogenesis of ovarian hyperstimulation syndrome is likely to be complex and may involve a network of interacting cytokines and endocrine factors. Recent studies suggest links between specific cytokines and specific functional abnormalities in severe ovarian hyperstimulation syndrome. Two clinical forms of ovarian hyperstimulation syndrome may be distinguished, based on time of onset, with implications for the prediction and prevention of ovarian hyperstimulation syndrome in clinical practice.


Highly Stable Zr(IV)-Based Metal-Organic Frameworks with Chiral Phosphoric Acids for Catalytic Asymmetric Tandem Reactions.
Heterogeneous Brønsted acid catalysts featuring high porosity, crystallinity, and stability have been of great interest for both fundamental studies and practical applications, but synthetically, they still face a formidable challenge. Here, we illustrated a ligand design strategy for directly installing chiral phosphoric acid catalysts into highly stable Zr-MOFs by sterically protecting them from coordinating with metal ions. A pair of chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2] were prepared from enantiopure 4,4',6,6'-tetra(benzoate) and -tetra(2-naphthoate) ligands of 1,1'-spirobiindane-7,7'-phosphoric acid. They share the same topological structure but differ in channel sizes, and both of them demonstrate excellent tolerance toward water, acid and base. Significantly enhanced Brønsted acidity was observed for the phosphoric acids that are uniformly distributed within the frameworks in comparison with the nonimmobilized acids. This not only facilitates the catalysis of asymmetric two-component tandem acetalization, Friedel-Crafts, and iso-Pictet-Spengler reactions but also promotes the catalysis of asymmetric three-component tandem deacetalization-acetalization and Friedel-Crafts reactions benefiting from the synergy with exposed Lewis acidic Zr(IV) sites. The enantioselectivities are comparable or favorable compared to those obtained from the corresponding homogeneous systems. The features of high reactivity, selectivity, stability, and recyclability for Zr(IV)-MOFs make them hold promise as a new type of heterogeneous acid catalyst for the eco-friendly synthesis of fine chemicals.


Touching sounds: thalamocortical plasticity and the neural basis of multisensory integration.
To date, noninvasive neuroimaging research on multisensory perception has focused on cortical activations. In a series of elegant functional magnetic resonance imaging experiments, Beauchamp and Ro recently investigated altered cortical activations associated with acquired sound-touch synesthesia resulting from a thalamic lesion. Their findings highlight the important role of intact thalamocortical projections for preventing illusory crossmodal perception and for underlying reliable multisensory integration.


Cell proliferation in N-nitrosodiethylamine (DEN)-treated rat liver parenchyma correlated with tumor development.
The authors wanted to clarify the relationship between the cell proliferation of the liver parenchyma and the development of hepatocellular carcinoma. Liver specimens of 22 N-nitrosodiethylamine-treated rats and 15 normal control rats were examined using laparotomic biopsies at 30 day intervals, followed by total liver resections after sacrifice. Magnetic resonance imaging was performed to evaluate the development of hepatocellular carcinoma at each period before biopsy. Cell proliferation was determined using the thymidine analogue, bromodeoxyuridine, which is taken up by S-phase cells during DNA synthesis. The cell proliferation of the liver parenchyma gradually increased by the 60th day after the initiation of nitrosodiethylamine administration. The labeling index on the 60th day was 0.33 +/- 0.10%. No abnormal mass lesions were identified in either the control rats or the nitrosodiethylamine-treated-rats within this period. By the 90th day in the nitrosodiethylamine-treated-rats, the labeling index of non-cancerous portion had rapidly increased by as much as 1.60 +/- 0.38%, and magnetic resonance imaging demonstrated small high signal intensity nodules on T1-weighted images. They were either hyperplastic nodules or well-differentiated hepato-cellular carcinomas. Moderately or poorly differentiated hepatocellular carcinomas developed at the 120th day. The cell proliferation of non-cancerous portion of nitrosodiethylamine-treated-rats livers increased immediately before the development of hepatocellular carcinomas. Detection of this rapid increase of cell proliferation in non-cancerous portions of the liver may suggest a high probability of development of hepatocellular carcinoma in the near future.


Neurotropic viral infections leading to epilepsy: focus on Theiler's murine encephalomyelitis virus.
Neurotropic viruses cause viral encephalitis and are associated with the development of seizures/epilepsy. The first infection-driven animal model for epilepsy, the Theiler's murine encephalomyelitis virus-induced seizure model is described herein. Intracerebral infection of C57BL/6 mice with Theiler's murine encephalomyelitis virus induces acute seizures from which the animals recover. However, once the virus is cleared, a significant portion of the animals that experienced acute seizures later develop epilepsy. Components of the innate immune response to viral infection, including IL-6 and complement component 3, have been implicated in the development of acute seizures. Multiple mechanisms, including neuronal cell destruction and cytokine activation, play a role in the development of acute seizures. Future studies targeting the innate immune response will lead to new therapies for seizures/epilepsy.


Estimating population access to insecticide-treated nets from administrative data: correction factor is needed.
Population access to insecticide-treated nets (ITN) is usually determined from survey data. However, for planning purposes it is necessary to estimate this indicator between surveys. Two different approaches are currently recommended for such estimates from administrative data, multiplying the number of ITN delivered either by 2.0 or 1.8 before dividing by the population. However, the validity of such estimates has not previously been investigated. Thirty-five datasets from household surveys in sub-Saharan Africa were selected from ten different countries. The number of ITN and de-facto population from the samples was used as proxy administrative data and estimates of population access to ITN were calculated using the recommended formulae. Administrative estimates were compared to the access indicator from the survey data. Regression analysis was used to further define the relationship between administrative and survey population access. Mean number of ITN users was determined for each data set separately for households with and without enough ITN. Analysis of users per ITN showed that the assumption of two users per net is valid overall (median 2.00) but that it was consistently lower in households with at least one ITN for every two people (median 1.66). Using the formula number of ITN times 2.0 divided by the population to estimate population access to ITN from administrative data generally overestimated the survey access indicator. This was particularly the case at higher coverage levels, resulting in a 30 percentage-point overestimate at survey access above 80%. Using 1.8 as the multiplier for the number of ITN from administrative data improved the results but still showed a 19 percentage-point overestimate at access coverage above 80%. Regression analysis found that a factor of 1.64 provides the best prediction of the access indicator with slight underestimation at low access levels but good fit at levels above 55%. A factor of 1.6 rather than 2.0 or 1.8 as the mean number of users per ITN provides a more accurate estimation of population access to ITN from administrative data accounting for discordant ITN-person pairs and a reduced number of ITN users when sufficient ITN are available.


Nociceptin/orphanin FQ peptide in hypothalamic neurones associated with the control of feeding behaviour.
Nociceptin/orphanin FQ (N/OFQ), an endogenous peptide agonist of the opioid N/OFQ receptor, has been implicated in the regulation of energy balance. In the present study, we have used immunohistochemistry to investigate the cellular localisation and colocalisation of N/OFQ-immunoreactive cell bodies in hypothalamic regions containing neurones producing orexigenic or anorexigenic transmitters. In colchicine-treated rats, N/OFQ immunoreactivity was demonstrated in many cell bodies of the arcuate nucleus (Arc), paraventricular nucleus (PVN) and lateral hypothalamic area (LHA). Double-labelling revealed that N/OFQ was present in some neurones located in the ventrolateral part of the Arc producing pro-opiomelanocortin, as shown by the presence of the anorexigenic peptides alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript and, occasionally, in single neurones of the ventrolateral Arc producing orexigenic agouti-related peptide, but not neuropeptide Y. N/OFQ immunoreactivity was also demonstrated in a few tyrosine hydroxylase- or dynorphin (DYN)-containing neurones in the dorsomedial part of the Arc. In the parvocellular PVN, N/OFQ was demonstrated in some thyrotrophin-releasing hormone- or DYN-, but not corticotrophin-releasing hormone-containing neurones. Most N/OFQ-immunoreactive neurones in the LHA contained orexin- and DYN, but not melanin-concentrating hormone. The results obtained, demonstrating the presence of N/OFQ in some alpha-MSH- and in many orexin-containing neurones, suggest a functional relationship between these neuropeptides and N/OFQ in the control of feeding behaviour and body weight.


Preoperative calculation of angles of vision and working area in laparoscopic surgery to treat a giant hiatal hernia.
Giant hiatal hernias still pose a major challenge to digestive surgeons, and their repair is sometimes a highly complex task. This is usually performed by laparoscopy, while the role of the thoracoscopic approach has yet to be clearly defined. To preoperatively detect patients with a giant hiatal hernia in whom it would not be safe to perform laparoscopic surgery and who, therefore, would be candidates for a thoracoscopic approach. In the present study, using imaging test we preoperatively simulate the field of vision of the camera and the working area (instrumental access) that can be obtained in each patient when the laparoscopic approach is used. From data obtained, we can calculate the access angles that will be obtained in a preoperative computerised axial tomography coronal section, according to the location of the trocar. We also provide the formula for performing the angle calculations If the trocars are placed in loss common situations, thus enabling us to determine the visibility and manoeuvrability for any position of the trocars. The working area determines the cases in which we can operate safely and those in which certain areas of the hernia cannot be accessed, which is when the thoracoscopic approach would be safer.


Nasal Cavity or Alveolar Paranasal Sinus Rhabdomyosarcoma with Orbital Extension in Adults: 2 Cases.
Alveolar rhabdomyosarcoma (RMS) has a predilection for the deep soft tissues of the extremities and mainly occurs in children. Although the tumor may originate in other sites, such as the nasal cavity or paranasal sinus, invasion of the orbit is unusual. We describe the clinicopathological features of 2 cases of alveolar RMS of the nasal cavity or paranasal sinus in adult patients with orbital extension. These cases of alveolar RMS of the nasal cavity or paranasal sinuses are described in 2 men, both in the third decade of life. These patients were evaluated with radiological studies. The histological diagnosis was confirmed by immunohistochemical methods. Treatment consisted in a combination of chemotherapy and radiation therapy following excisional biopsy. Alveolar subtype RMS is an extremely aggressive neoplasm that rarely presents in the orbit or paranasal sinuses of adults but should be considered in the differential diagnosis of tumors with this localization. Myoglobin, Myo D1, and myogenin seem to be the most specific markers for RMS.


Novel aspects of epitope matching and practical application in kidney transplantation.
This review describes the recent developments in the applicability and clinical significance of epitope matching in kidney transplantation. As incremental human leukocyte antigen (HLA) mismatches are associated with increased risk of rejection and allograft loss, HLA-matching remains one of the standard immunological triage tests to determine transplant suitability. Advancements in tissue-typing techniques have led to innovative concepts of HLA-matching at the epitope level. Epitopes are configurations of polymorphic amino acid residues that are recognized by B cells, and antibodies reactive with these epitopes lead to rejection and/or premature allograft loss. Even though there is substantial advancement in the characterization and understanding of epitopes, evidence supporting the added clinical benefit of epitope matching over traditional antigen matching and the ability to identify clinically relevant immunogenic epitopes remains poorly defined. We present an overview of the evidence surrounding the immunogenicity of mismatched donor epitopes and the applicability of HLA epitope matching in kidney transplantation. A better understanding of the immunogenicity and structural characteristics of HLA epitopes will guide clinicians to integrate epitope matching as an important parameter for donor selection in kidney transplantation.


[Dictyostelium discoideum: a model for the study of bacterial virulence].
The amoeba Dictyostelium discoideum, a bacterial predator, has emerged as a valuable tool for studying bacterial virulence. All its features make this unicellular eukaryote a versatile model organism. It can be used to study virulence factors of pathogenic bacteria as well as host elements involved in resistance to pathogens. The virulence of more than 20 bacterial species pathogenic for humans or animals has been studied using D. discoideum so far. These bacteria are either extracellular or intracellular pathogens. This review presents an overview of the question, with special emphasis on the reasons why D. discoideum is a suitable host model to study bacterial virulence, as well as on the type of information on host–pathogen relationship this amoeba can provide.


Influence of reaching direction on visuomotor adaptation: an explorative study.
Robotics is increasingly used in rehabilitation therapy of the hemiparetic arm after stroke. Several studies performed adaptation experiments to gain more insight in the underlying learning processes. In these studies adaptation during reaching movements in different directions is assessed. No information about influence of direction on the amount of learning to these separate directions is present. In this paper we assessed the effect of reaching direction on visuomotor learning. Forty healthy subjects performed 48 movements to five different directions during adaptation to a 30 degrees visuomotor rotation. The execution error was defined as the initial direction error at peak velocity and after 100 ms after onset of the movement. The amount of learning was defined as the difference between the start value and the end value of the execution error. A significant higher amount of adaptation in the movement towards the contralateral part of the body (-72) compared to reaching towards other directions was observed. When possible feedback and corrections mechanisms are taken into account; results indicate that subjects adapt most towards -72 direction and least towards -144 direction. Data of healthy elderly and stroke survivors would be essential to test whether observed results are present in these populations as well, which could have implications for motor relearning in rehabilitation therapy.


Gonococcal porin IB activates NF-kappaB in human urethral epithelium and increases the expression of host antiapoptotic factors.
Infection of human urethral epithelial cells (UECs) with Neisseria gonorrhoeae increases the transcription of several host antiapoptotic genes, including bfl-1, cox-2, and c-IAP-2. In order to identify the bacterial factor(s) responsible for eliciting these changes, the transcriptional status of apoptotic machinery was monitored in UECs challenged with certain gonococcal membrane components. Initially, we observed that infection of UECs with gentamicin-killed gonococci increased the expression of the antiapoptotic Bcl-2 family member, bfl-1. This observation indicated that viable, replicating bacteria are not required for induction of antiapoptotic gene expression. Confirming this observation, treatment of UECs with purified gonococcal membrane increased the expression of bfl-1, cox-2, and c-IAP-2. This finding suggested that a factor or multiple factors present in the outer membrane (OM) are responsible for altering UEC antiapoptotic gene expression. Interestingly, treatment of UECs with gonococcal porin IB (PorB IB), a major constituent of the OM, significantly increased the transcription of bfl-1, cox-2, and c-IAP-2. The upregulation of these genes by PorB IB was determined to be dependent on NF-kappaB activation, as inhibiting NF-kappaB blocked induced expression of these genes. This work demonstrates the altered expression of host apoptotic factors in response to gonococcal PorB IB and supports a model whereby UEC cell death may be modulated as a potential mechanism of bacterial survival and proliferation.


[Apomorphine in advanced Parkinson disease].
Apomorphine is the most potent dopamine receptor agonist and its symptomatic effectiveness is comparable to levodopa. Subcutaneous apomorphine is rapidly and completely absorbed. Plasma peak concentrations are achieved after 5-15 minutes and onset of clinical effect is within 20 minutes. Apomorphine intermittent subcutaneous injections are effective as rescue therapy for unpredictable off periods in advanced Parkinson disease (PD). More often apomorphine is administered as a subcutaneous infusion which secures the continuous dopaminergic stimulation. The benefit on 'off' periods is consistent across all studies, but dyskinesia improvement is not so obvious. Two infusion therapies (apomorphine and intraduodenal levodopa) and deep brain stimulation (DBS) are effective in advanced PD patients with untreatable motor complications. Apomorphine infusions should be considered in patients unable to undergo DBS because of cognitive impairment and neurosurgical contraindications.


New prescription of antihyperglycemic agents among patients with diabetes in Germany: Moderate concordance between health insurance data and self-reports.
To analyze the concordance of new prescription of antihyperglycemic agents between two data sources: patients' self-reports and statutory health insurance (SHI) data among patients with diabetes. Within a cross-sectional study, 494 patients with diabetes were interviewed if and which new prescriptions of diabetes medication they received within the last 3 or 6 months. SHI data for 12 months were linked to cover these periods. For the agreement measurement, SHI data was set as reference, and kappa, positive predictive value (PPV), and sensitivity were calculated for single Anatomical Therapeutic Chemical (ATC) codes and cumulated code groups. The number of new prescriptions within 3 or 6 months was low, with 5.5% (n = 27) for Metformin/self-report being the highest. Contingency tables were unbalanced and showed large numbers in the no/no-cells. Regarding non-agreement, we found new prescriptions slightly more often in SHI data only than in self-reports only, with insulin and metformin representing an exception. Agreement results were moderate with large confidence intervals (CI). The values for cumulated "all drugs in diabetes" were: kappa = 0.58 (95% CI: 0.51-0.65), PPV = 62.0 (53.4-70.2), sensitivity = 55.6 (47.3-63.6). Patients reported a low number of new prescriptions within the last 3 or 6 months. In general we found moderate agreement and in case of non-agreement that self-report no/SHI yes was slightly more frequent than vice versa. These results were based on small case numbers, but could nevertheless be considered when collecting self-reported information on the prescription of antihyperglycemic agents.


Uncovering early response to drought by proteomic, physiological and biochemical changes in the almond × peach rootstock 'Garnem'.
Drought affects growth and metabolism in plants. To investigate the changes in root protein function involved in the early response to drought stress, a proteomic analysis in combination to a physiological and biochemical analysis was performed in plants of 'Garnem', an almond × peach hybrid rootstock, subjected to short-term drought stress. Abscisic acid (ABA) accumulation levels increased during the drought exposure, which induced stomatal closure, and thus, minimised water losses. These effects were reflected in stomatal conductance and leaf water potential levels. However, 'Garnem' was able to balance water content and maintain an osmotic adjustment in cell membranes, suggesting a dehydration avoidance strategy. The proteomic analysis revealed significant abundance changes in 29 and 24 spots after 2 and 24 h of drought stress respectively. Out of these, 15 proteins were identified by LC-ESI-MS/MS. The abundance changes of these proteins suggest the influence in drought-responsive mechanisms present in 'Garnem', allowing its adaptation to drought conditions. Overall, our study improves existing knowledge on the root proteomic changes in the early response to drought. This will lead to a better understanding of dehydration avoidance and tolerance strategies, and finally, help in new drought-tolerance breeding approaches.


Time course of occlusive effects on skin evaluated by measurement of transepidermal water loss (TEWL). Including patch tests with sodium lauryl sulphate and water.
The time course for transepidermal water loss (TEWL) for a period of 3 h after removal of occlusive patch tests with sodium lauryl sulphate (SLS), water and empty chambers was studied in healthy volunteers. Patches were applied to the upper arm for 24 h. TEWL was measured immediately after removal of the patches, and every 30 min up to 3 h. For SLS and water patches, TEWL remained significantly increased for 3 h, as compared to normal adjacent skin, while for empty chamber patches, TEWL was only significantly increased for 30 min. A significant decrease from 0 to 30 min and from 30 to 60 min was observed for all patches, and for water patches, a significant decrease in TEWL was found from 60 to 180 min, while SLS patches remained constant. The prolonged increase in TEWL observed after SLS exposure is a well-known occurrence. The prolonged increase in TEWL after exposure to water is interpreted as transient damage to the water barrier of the skin.


[Effect of photocoagulation on retinal mean circulation time in proliferative diabetic retinopathy by use of fluorescein video angiography and image analysis system].
The effect of panretinal photocoagulation (PRP) on mean circulation time (MCT) was investigated in a main nasal superior artery and vein of 13 eyes with proliferative diabetic retinopathy, using fluorescein video angiography and an image analysis system. MCT before photocoagulation averaged 5.67 +/- 1.40 seconds. Two weeks after PRP, MCT averaged 4.29 +/- 0.89 sec., one month after, 4.29 +/- 0.88 sec., three months after, 4.03 +/- 0.86 sec., and six months after, 3.61 +/- 0.31 sec. The MCTs after PRP were shorter than MCT before PRP (p less than 0.01). These results suggest that MCTs in proliferative diabetic retinopathy shortened soon after PRP.


Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idiopathic Parkinson's disease.
The efficacy and safety of oral Sildenafil, a potent inhibitor of phosphodiesterase type 5, were evaluated in depressed men with idiopathic Parkinson's disease and erectile dysfunction. Thirty-three men were enrolled in a 4-month prospective, open-label, fixed-dose study, and received 50mg of Sildenafil in the home setting approximately 1 hour before sexual activity, not more than once daily. Efficacy was determined by responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) of the 15-item International Index of Erectile Function (IIEF). Other measures of efficacy included the five sexual function domains of IIEF, a global efficacy question, the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale-21 (HDRS-21). At the end of the study, improved erections were reported by 84.8% of patients. Sildenafil significantly increased patients' ability to achieve and maintain erections. Significant improvements were also observed in the IIEF domains for erectile function, orgasmic function, intercourse satisfaction and overall sexual satisfaction. BDI and HDRS scores improved from baseline to the end of the study. A clear improvement of depressive symptoms was observed in 75% of patients. Sildenafil was well tolerated in all the patients. Treatment with oral Sildenafil improves erectile function and, indirectly, depressive symptoms in patients with idiopathic Parkinson's disease stages 1-3, and is well tolerated.


A 'pocket guide' to total internal reflection fluorescence.
The phenomenon of total internal reflection fluorescence (TIRF) was placed in the context of optical microscopy by Daniel Axelrod over three decades ago. TIRF microscopy exploits the properties of an evanescent electromagnetic field to optically section sample regions in the close vicinity of the substrate where the field is induced. The first applications in cell biology targeted investigation of phenomena at the basolateral plasma membrane. The most notable application of TIRF is single-molecule experiments, which can provide information on fluctuation distributions and rare events, yielding novel insights on the mechanisms governing the molecular interactions that underpin many fundamental processes within the cell. This short review intends to provide a 'one stop shop' explanation of the electromagnetic theory behind the remarkable properties of the evanescent field, guide the reader through the principles behind building or choosing your own TIRF system and consider how the most popular applications of the method exploit the evanescent field properties.


Mechanisms by Which Atopic Dermatitis Predisposes to Food Allergy and the Atopic March.
The Atopic march denotes the progression from atopic dermatitis (AD) to the development of other allergic disorders such as immunoglobulin (Ig) E-mediated food allergy, allergic rhinitis and asthma in later childhood. There is increasing evidence from prospective birth cohort studies that early-onset AD is a risk factor for other allergic diseases or is found in strong association with them. Animal studies now provide mechanistic insights into the pathways that may be responsible for triggering the progression from the skin barrier dysfunction seen in AD to epicutaneous sensitization, food allergy and allergic airway disorders. Recent large randomized controlled trials have demonstrated the efficacy of early interventions targeted at AD and food allergy prevention. These show great promise for research into future strategies aimed at prevention of the atopic march.


Smoking in a forensic psychiatric service: a survey of inpatients' views.
Smoking in a forensic psychiatric service: a survey of inpatients' views Very little is known concerning the views and beliefs of psychiatric inpatients about smoking in hospital. We conducted a survey of inpatients from the forensic wards of a large independent psychiatric hospital using a structured interview to collect data about their views on smoking. Of 102 patients eligible to participate, 45 (44.1%) agreed to do so. Most participants (34, 75.6%) were current smokers. Most smokers thought it was just too difficult to give up smoking (25, 73.5%). They cited seeing staff and other patients smoking, as well as the smoky atmosphere on the ward, as barriers to quitting. The majority of participants (35, 77.8%) thought that staff should be allowed to smoke with patients. Smokers held more liberal views about smoking than non-smokers. A smaller proportion of non-smokers than smokers were happy with the hospital smoking policy, as reflected in the ward rules about smoking. The results of this survey suggest that a change in attitude and culture towards smoking may be needed in psychiatric units. Smokers should be regularly offered help and encouragement to quit. Psychiatric care staff should carefully consider whether their own smoking behaviour undermines their patients' attempts to stop smoking. More attention should be given to the views and needs of non-smokers.


The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis.
The determinants of cancellous bone turnover and trabecular structure are not understood in normal bone or skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor kappaB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.


Lactucaxanthin Regulates the Cascade of Retinal Oxidative Stress, Endoplasmic Reticulum Stress and Inflammatory Signaling in Diabetic Rats.
The purpose of this study is to investigate the protective mechanism of lactucaxanthin against retinal angiogenesis in diabetic retinopathy. Streptozotocin-induced diabetic rats were orally gavaged with either lactucaxanthin or lutein (n=12/group) for 8 weeks. Serum and retina collected from euthanized rats were subjected to assess oxidative stress, ER stress and inflammatory response. Lactucaxanthin administration was found to lower oxidative stress markers (protein carbonylation and lipid peroxidation) by augmenting antioxidant activity expression and ameliorated VEGF-A levels in diabetic group. Likewise, it suppressed the expression of ER stress (ATF4, ATF6, and XBP1), and inflammatory (TNF-α, IL-6, NF-κB, and ICAM-1) markers in diabetic retina. In addition, lactucaxanthin improved glucose tolerance and lipid profile under diabetic condition and suppressed the crosstalk between OS, ER stress, and inflammation. Lactucaxanthin could be used as a promising therapeutic bioactive for treating DR condition, and retinal angiogenesis. Limitation of the study includes the sample size and the duration of treatment. Despite these limitations, this study has revealed the potential of lactucaxanthin in treating eye related diabetic complications. To validate the results obtained from this study, clinical study must be performed to understand the relative benefit of lactucaxanthin in DR treatment.


Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation and valvular heart disease.
We compared the effectiveness and safety outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients with AF and VHD, as these patients have been partially excluded from clinical trials. This retrospective cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients with AF and VHD and above 20 years of age, who were prescribed oral anticoagulants such as warfarin, dabigatran, rivaroxaban, and apixaban, were included. Propensity score matching was performed to balance intergroup differences. The Cox proportional hazards model was used to compare the effectiveness and safety of warfarin and NOACs. We included 5833 NOAC-warfarin pairs, 3001 dabigatran-warfarin pairs and 2595 rivaroxaban-warfarin pairs. Warfarin and NOACs had similar risk of ischemic stroke (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.79-1.06; p = .25) and bleeding events (HR, 0.90; 95% CI, 0.78-1.02; p = .10). NOACs showed reduced risk of venous thromboembolism, intracranial hemorrhage, and mortality (HR and 95% CI, 0.39 [0.20-0.77], p = .01; 0.62 [0.45-0.84], p < .01; and 0.47 [0.41-0.53], p < .01, respectively). The benefit of NOACs in reducing the risk of venous thromboembolism was mainly driven by dabigatran, and the benefit of reducing the risk of intracranial hemorrhage and mortality was observed in both dabigatran and rivaroxaban users. NOACs had a comparable risk of ischemic stroke and bleeding in patients with AF and VHD, and reduced the risk of venous thromboembolism, intracranial hemorrhage, and mortality, compared to warfarin. Therefore, NOAC is an effective and safe alternative to warfarin in these patients.


Acceleration of Enamel Subsurface Lesion Remineralisation by Intralesion pH Modulation.
Remineralisation of demineralised enamel subsurface lesions can be enhanced by pretreatment of the lesions with base (NaOH). The aim of this study was to test the effect of intralesion pH modulation on remineralisation of demineralised enamel subsurface lesions by casein phosphopeptide-stabilised amorphous calcium fluoride phosphate (CPP-ACFP) in vitro. Two remineralisation models were utilised, the first involving 60-min cyclic pH modulation for 105 h and the second involved short-term cyclic pH modulation (12-min cycle, 240 min total duration) compared with the equivalent time of continuous treatment (200 min total duration). The intralesion pH modulation was achieved by cyclic exposure to a pH 12.9 NaOH solution and a CPP-ACFP remineralisation solution at pH 5.5. Percent remineralisation was assessed using transverse microradiography with data statistically analysed using a 2-sample Student t test. For the first model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (43.8 ± 6.9%) than the control group (28.2 ± 5.8%) cycled with water. For the second model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (23.1 ± 3.4%) than the group with continuous equivalent CPP-ACFP treatment time (1.9 ± 1.3%). In both models, intralesion pH modulation significantly accelerated remineralisation, and this was attributed to the effect pH modulation had on the diffusion gradients of ions/ion pairs and the degree of saturation with respect to apatite phases within the lesion fluid.


A drug utilization review of prescribing patterns for trazodone versus amitriptyline.
The second-generation antidepressant trazodone has been thought by some clinicians to exert a less robust antidepressant effect than do tricyclic agents. This impression differs from the findings of numerous published clinical trials. In an effort to determine whether this discrepancy may be due to possible inappropriate dosing or use of trazodone for different patient subtypes, a retrospective chart review of 138 depressed inpatients treated with amitriptyline and of 42 depressed inpatients treated with trazodone was performed to compare their respective prescribing patterns. While these two groups did not differ with regard to most demographic variables, results revealed that patient prescribed trazodone were older (trazodone, mean +/- SD age = 54.5 +/- 8.8 years versus amitriptyline, 43.2 +/- 12.9 years; p less than .001), more often had a recurrent depressive disorder (trazodone = 57.1%, amitriptyline = 39.1%, p less than .06), and more frequently had a history of unresponsiveness to other antidepressants (trazodone = 47.6%, amitriptyline = 11.6%; p less than .001). In addition, initially prescribed daily doses of trazodone were below the recommended starting dose of 150 mg/day (mean +/- SD starting dose = 113.7 +/- 42.1 mg/day), while starting daily doses for amitriptyline (mean +/- SD = 69.8 +/- 20.1 mg/day) were judged to be more adequate relative to the recommended daily dose of 75 mg/day. Final trazodone dosage (mean +/- SD final dose = 217.9 +/- 87.5 mg/day) could be judged to have been far short of optimal levels of 250 to 350 mg/day and of up to 600 mg/day for inpatients and 400 mg/day for outpatient.(ABSTRACT TRUNCATED AT 250 WORDS)


Susceptibility of plants to vascular disruption by macromolecules.
The xylem of alfalfa (Medicago sativa L.) was found to be susceptible to vascular obstruction by picomole quantities of dextrans. Not all parts of the xylem were equally susceptible to this plugging. The quantity of dextran of 2 x 10(6) molecular weight required to stop vascular flow was 8 picomoles in petiole junctions and 0.4 picomole in leaflet veins. Vascular flow through stems was greatly reduced but not stopped, even by over 150 picomoles of the dextran. The ability of dextrans to interfere with vascular conductance was directly correlated with their molecular weight. Dextrans of molecular weight less than 250,000 had little ability to stop vascular flow.


A single pacemaker can produce different rates of reentrainment in different overt rhythms.
Using a simple Van der Pol oscillator, we show that periodic events triggered by different states of the oscillator can reentrain at different rates following a phase shift of the Zeitgeber. Such differences can emerge due to waveform distortion during reentrainment, due to masking and due to fitting procedures (e.g. acrophase determination). Therefore, different rates of reentrainment are consistent with single pacemaker models of circadian systems. Likewise, "Fractional Desynchronization" can yield different "ranges of entrainment" in different overt rhythms generated by the same pacemaker.


[Dietary and hygienic aspects of fluoride exposure in pregnant women].
The study was undertaken to assess the exposure of pregnant women to fluoride on the basis of diet preferences and hygienic habits revealed with a questionnaire. The group included 59 women aged 22-39, living in a large urban agglomeration. Questions concerned sources of fluoride such as diet (tap water, tea, fish, poultry), use of fluoride-containing preparations for oral hygiene and substances containing fluoride for additional prophylaxis. The oral health status was clinically examined and caries intensity was assessed with the mean DMF-t index. According to the clinical examination, the mean DMF-t index was 13.64 and ranged from 1 to 23. Consumption of tap water averaged 0.73 L (max. 2.5 L), including 0.55 L (max. 2.5 L) of tea. Poultry was a regular part of the diet in only 14 of the respondents (24%) and only 3 (5%) sporadically (once a week) ate ocean fish. All the respondents used toothpaste containing fluoride, but only 15.3% applied professional prophylaxis with fluoride preparations. As far as the diet is concerned, individual differences in the intake of fluorides were significant. Interestingly, despite the declared everyday use of fluorine-containing toothpaste, the caries intensity index was rather high, suggesting the need for special dental care in this group of patients.


Systemic vasculitis: an underestimated cause of heart failure - assessment by cardiovascular magnetic resonance.
Cardiovascular manifestations in systemic vasculitis include initially silent cardiomyopathy due to either ischemic or inflammatory causes. The combination of vasculitis and cardiomyopathy is associated with a poor prognosis. Early treatment with immunosuppressants in conjunction with appropriate cardiac pharmacotherapy is considered important and has dramatically improved prognosis. Cardiovascular magnetic resonance, due to its nonionizing, noninvasive evaluation of the cardiovascular system, can be of great value in the diagnosis, follow-up, and treatment of patients with systemic vasculitis.


Ovarian vein thrombosis in the antiphospholipid syndrome.
Ovarian vein thrombosis (OVT) is an unusual condition mainly observed during the postpartum period. It has not been reported to date in the antiphospholipid syndrome. Two female patients with definite antiphospholipid syndrome, ages 33 years and 73 years, were diagnosed as having OVT by computed tomography (CT) scan, according to the radiologic criteria described by Zerhouni et al. In 1 of the women, the left vein was affected by OVT, while in the other woman, the right vein was affected. One of the patients had a pulmonary embolism; the diagnosis of OVT was established after she underwent a cesarean section and a right atrium thrombectomy. The other patient had no vascular manifestations. OVT was asymptomatic in both patients. Searches for associated thrombophilic states yielded negative results. With the continuation of anticoagulation therapy, the 2 patients have remained in good condition. Resolution of the OVT was observed in the patient who underwent a CT scan during followup. To our knowledge, this is the first report of OVT occurring in the antiphospholipid syndrome. Given that it may develop in the absence of pelvic clinical manifestations, this complication may be underdiagnosed.


Copper-Polyurethane Composite Materials: Particle Size Effect on the Physical-Chemical and Antibacterial Properties.
In this work, thermoplastic polyurethane (TPU) composites incorporated with 1.0 wt% Cu particles were synthesized by the melt blending method. The effect of the incorporated copper particle size on the antibacterial, thermal, rheological, and mechanical properties of TPU was investigated. The obtained results showed that (i) the addition of copper particles increased the thermal and mechanical properties because they acted as co-stabilizers of polyurethane (PU) (ii) copper nanoparticles decreased the viscosity of composite melts, and (iii) microparticles > 0.5 µm had a tendency to easily increase the maximum torque and formation of agglomerates. SEM micrographics showed that a good mixture between TPU and copper particles was obtained by the extrusion process. Additionally, copper-TPU composite materials effectively inhibited the growth of the Gram-negative Escherichia coli and the Gram-positive Staphylococcus aureus. Considering that the natural concentration of copper in the blood is in the range of 0.7-0.12 mg/L and that the total migration value of copper particles from TPU was 1000 times lower, the results suggested that TPU nanocomposites could be adequately employed for biomedical applications without a risk of contamination.


The myostatin gene is a downstream target gene of basic helix-loop-helix transcription factor MyoD.
Myostatin is a negative regulator of myogenesis, and inactivation of myostatin leads to heavy muscle growth. Here we have cloned and characterized the bovine myostatin gene promoter. Alignment of the upstream sequences shows that the myostatin promoter is highly conserved during evolution. Sequence analysis of 1.6 kb of the bovine myostatin gene upstream region revealed that it contains 10 E-box motifs (E1 to E10), arranged in three clusters, and a single MEF2 site. Deletion and mutation analysis of the myostatin gene promoter showed that out of three important E boxes (E3, E4, and E6) of the proximal cluster, E6 plays a significant role in the regulation of a reporter gene in C(2)C(12) cells. We also demonstrate by band shift and chromatin immunoprecipitation assay that the E6 E-box motif binds to MyoD in vitro and in vivo. Furthermore, cotransfection experiments indicate that among the myogenic regulatory factors, MyoD preferentially up-regulates myostatin promoter activity. Since MyoD expression varies during the myoblast cell cycle, we analyzed the myostatin promoter activity in synchronized myoblasts and quiescent "reserve" cells. Our results suggest that myostatin promoter activity is relatively higher during the G(1) phase of the cell cycle, when MyoD expression levels are maximal. However, in the reserve cells, which lack MyoD expression, a significant reduction in the myostatin promoter activity is observed. Taken together, these results suggest that the myostatin gene is a downstream target gene of MyoD. Since the myostatin gene is implicated in controlling G(1)-to-S progression of myoblasts, MyoD could be triggering myoblast withdrawal from the cell cycle by regulating myostatin gene expression.


Interference of cartilage surface with interaction of granulocyte elastase with alpha 1-proteinase inhibitor. An in vitro model of enzyme inhibition in the joint space.
Synovial fluids of patients suffering from rheumatoid arthritis contain elevated levels of granulocyte (PMN) elastase in complex with alpha 1-proteinase inhibitor (alpha 1-PI), whereas free-elastase activity is usually not detectable. This absence of free enzymatic activity in joint effusions has cast some doubt on the pathophysiological relevance of PMN elastase in inflammatory joint destruction. Our in vitro experiments using bovine nasal cartilage demonstrate that incubation with elastase and alpha 1-PI in equimolar concentrations to or even in excess of the serum proteinase inhibitor resulted in significant tissue destruction as assessed by histological staining for proteoglycans, release of uronic acid from the matrix and loss of mechanical stability. Though in the supernatants containing alpha 1-PI, free-elastase activity was not detectable, immunofluorescent staining for elastase evidenced penetration of the enzyme into the matrix. Simultaneous measurements of the incubation media employing a sandwich enzyme-linked immunoadsorption assay (ELISA) revealed PMN elastase in complex with alpha 1-PI but without correlation to the parameters of tissue degradation. In comparison with the results obtained using the chromogenic substrate Suc-Ala-Ala-Ala-pNA (SAPA) for titration of alpha 1-PI against elastase, the employment of cartilage matrix showed that a fourfold increase in inhibitor concentration was necessary to achieve 100% enzyme inhibition. Hence, cartilage surface obviously interferes with the interaction between alpha 1-PI and elastase. Measurements of elastase-inhibitor concentrations or free enzymatic activity in synovial fluid seem to have limited value in predicting cartilage destruction.


Systematic characterisation of secondary metabolites from Ixeris sonchifolia by the combined use of HPLC-TOFMS and HPLC-ITMS.
Ixeris sonchifolia (Bunge) Hance, a folk medicine, has been widely used in China for its anti-inflammatory and haemostatic effects. However, the miscellaneous component composition of this herbal medicine is not well known. To develop a fast and comprehensive analytical method for the characterisation of various components from I. Sonchifolia, as a tool for the quality control of the herb and its related preparations. Ixeris sonchifolia samples were extracted with 60% aqueous methanol, purified by solid-phase extraction and then analysed by the combinatorial use of HPLC-TOFMS and HPLC-ITMS. A total of six sesquiterpene lactones, six phenolic acids and seven flavonoids were identified or tentatively characterised. Five of them were reported for the first time in I. sonchifolia and, in particular, two amino acid-sesquiterpene lactone conjugates, 11,13-dihydro-13-prolyl-ixerin Z and 11,13-dihydro-13-prolyl-ixerin Z(1), that were first found in this plant source. A global profile of I. sonchifolia constituents was described, which could be useful for the quality control of this herb and its related preparations. The employed combination of HPLC-TOFMS and HPLC-ITMS could also be a promising tool for the analysis of other herbal medicines containing sesquiterpene lactones, phenolic acids or flavonoids.


[Profiles of type 1 and type 2 T cells in chronic idiopathic thrombocytopenic purpura].
To explore the profiles of type 1 and type 2 T cells in chronic idiopathic thrombocytopenic purpura (ITP) patients. Samples of peripheral blood were collected from 30 chronic ITP patients, 8 males and 22 females, aged 34, 20 being in the active stage, and 10 in the remission stage, and 20 healthy persons, 7 males and 13 females, aged 31. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and activated with PMA/ionomycin. Flow cytometry was used to measure the intracellular cytokines interferon (IFN)-gamma and interleukin (IL)-4 in the PBMCs so as to identify the Th1 cells (IFN-gamma(+) IL-4(+) CD4(+) cells), Th2 cells (IFN-gamma(-) IL-4(+) CD4(+) cells), Tc1 cells (IFN-gamma+ IL-4(-) CD8(+) cells), and Tc2 cells (IFN-gamma(-) IL-4(+) CD8(+) cells). The ratios of Th2/Tc2, Th1/Th2, and Tc1/Tc2 were calculated. Samples of spleen tissue were collected from 8 patients with chronic ITP, 3 males and 5 females, aged 30, and 6 patients with hereditary spherocytosis (HS), 3 males and 3 females, aged 35, who underwent splenectomy. Splenocytes were isolated, cultured, and activated with PMA/ionomycin. Real-time PCR was used to detect the mRNA expression of T-bet and GATA-3 in the PBMCs and splenocytes. The Th1/Th2 ratio of the patients in active stage was 25.62, significantly higher than those of the patients in remission stage (9.86) and the control (8.29, both P < 0.01), and the Tc1/Tc2 ratio of the patients in active stage was 30.23, significantly higher than those of the patients in remission stage (10.10) and the controls (12.58, both P < 0.01). The Th1/Th2 ratio of the splenocytes of the patients in active stage was 41.46, significantly higher than that of the controls (16.30, P < 0.01), and the Tc1/Tc2 ratio of the splenocytes of the active ITP patients was 35.80, not significantly higher than that of the controls (16.30, P = 0.082). The GATA-3 mRNA expression level of the PBMCs of the active ITP patients was one-fifth of that of the controls (P < 0.05) and the GATA-3 mRNA expression level of the splenocytes of the ITP patients was 0.34 of that of the HS patients (P < 0.05), however, there was no difference in the T-bet expression among the 3 groups. The T-bet/GATA-3 ratio of the PBMCs of the active ITP patients was 5.85 times that of the controls and the T-bet/GATA-3 ratio of the splenocytes of the active ITP patients was 2.68 times that of the controls (both P < 0.01). ITP is a T1 cells (Th1 and Tc1) predominant disease. The T-bet/GATA-3 ratio may provide a surrogate marker of T1/T2 cytokine balance. Shifting the cytokine patterns from T1 to T2 may be a potential immunotherapy for ITP.


Size control of ZnO nanorod arrays grown by metalorganic chemical vapour deposition.
The size control of vertically aligned ZnO nanorod arrays (NRAs) grown by catalyst-free metalorganic chemical vapour deposition is accomplished by changing the O/Zn precursor ratio. At a higher O/Zn precursor ratio, fat ZnO NRAs with excellent alignment are produced. In contrast, slim ZnO NRAs that are considerably less well aligned grow at a lower O/Zn precursor ratio. Irrespective of their different sizes and alignments, the individual ZnO nanorods are of a defect-free single-crystalline nature and of high optical quality, indicating that changing the precursor ratio is a promising way of fabricating size-controlled ZnO NRAs.


Genotypic analysis of Escherichia coli strains from poultry carcasses and their susceptibilities to antimicrobial agents.
Plasmid profiling and amplified fragment length polymorphism (AFLP) analysis were used to genotype 50 Escherichia coli strains from poultry carcasses. Thirty different plasmid profiles were evident, and clustering of the AFLP data showed that they were a distinctly heterogeneous group of strains. Susceptibility testing against five antimicrobial agents used in the South African poultry industry showed all strains to be susceptible to danofloxacin and colistin, while the majority (96%) were resistant to two tetracyclines.


Long-term results of Danish Prostatic Cancer Group trial 86. Goserelin acetate plus flutamide versus orchiectomy in advanced prostate cancer.
In a multicenter trial conducted by the Danish Prostatic Cancer Group, 264 patients with advanced prostate cancer were randomized either to undergo bilateral orchiectomy or to receive combination treatment with goserelin acetate and flutamide. This report is an update of that study, covering a median follow-up for survival of 57 months. Of 262 patients who were evaluated, 208 have died. As noted in earlier analyses of this study, no differences in time to progression and cause-specific and overall survival could be identified between the two treatment groups. In conclusion, the combination of goserelin and flutamide was not clinically superior to bilateral orchiectomy in the treatment of advanced prostate cancer.


Qizhi Kebitong Formula Ameliorates Streptozocin-Induced Diabetic Osteoporosis through Regulating the PI3K/Akt/NF-κB Pathway.
Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1β. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.


Coupled nanoantenna plasmon resonance spectra from two-photon laser excitation.
We report on the two-photon excitation and subsequent plasmonic mode relaxation of coupled optical gold nanoantennas. Using pulsed laser excitation at a constant wavelength of 810 nm, we observe two-photon-induced plasmon emission spectra, find them to match dark-field microscopy scattering spectra, and show that the emission intensity is enhanced by up to a factor of 65 compared to single gold rods of equal dimensions. This study shows the link of nonlinear optical excitation schemes with radiative relaxation pathways that match plasmonic mode emission of resonant optical gold antennas.


A dimensional and categorical approach to the symptomatology of recent-onset schizophrenia.
Sixty-five patients with recent-onset schizophrenia were assessed with two widely used symptom scales, the Brief Psychiatric Rating Scale-Expanded (BPRS-E) and the Psychiatric Assessment Scale (Manchester scale). Principal components analysis of the BPRS-E scores yielded a four-dimensional structure: positive symptoms, negative symptoms, disorganization, and depression. With the Psychiatric Assessment Scale, three dimensions were found: the positive symptoms (delusions, hallucinations) and disorganization (incoherence) appeared in one dimension. A categorical analysis resulted in predominantly positive, negative, and disorganized clusters, but more than half of the sample could not be allocated to any of these groups.


Neural correlates of emotion regulation in the ventral prefrontal cortex and the encoding of subjective value and economic utility.
In many studies of the interaction between cognitive control and emotion, the orbitofrontal cortex/ventromedial prefrontal cortex (mOFC/vmPFC) has been associated with an inhibitory function on limbic areas activated by emotionally arousing stimuli, such as the amygdala. This has led to the hypothesis of an inhibitory or regulatory role of mOFC/vmPFC. In studies of cognition and executive function, however, this area is deactivated by focused effort, raising the issue of the nature of the putative regulatory process associated with mOFC/vmPFC. This issue is here revisited in light of findings in the neuroeconomics field demonstrating the importance of mOFC/vmPFC to encoding the subjective value of stimuli or their economic utility. Many studies show that mOFC/vmPFC activity may affect response by activating personal preferences, instead of resorting to effortful control mechanisms typically associated with emotion regulation. Based on these findings, I argue that a simple automatic/controlled dichotomy is insufficient to describe the data on emotion and control of response adequately. Instead, I argue that the notion of subjective value from neuroeconomics studies and the notion of attentional orienting may play key roles in integrating emotion and cognition. mOFC/vmPFC may work together with the inferior parietal lobe, the cortical region associated with attentional orienting, to convey information about motivational priorities and facilitate processing of inputs that are behaviorally relevant. I also suggest that the dominant mode of function of this ventral network may be a distinct type of process with intermediate properties between the automatic and the controlled, and which may co-operate with effortful control processes in order to steer response.


Sex differences, developmental changes, response to injury and cAMP regulation of the mRNA levels of steroidogenic acute regulatory protein, cytochrome p450scc, and aromatase in the olivocerebellar system.
Compelling evidence has now demonstrated direct biological actions of sex steroids at the cerebellum. Likewise, the expression of key steroidogenic factors, such as the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage (P450scc), and aromatase, at this neural site has been reported. Little is known, however, about the regulation of their genes in the cerebellum. Assessment of StAR, P450scc, and aromatase mRNAs in the cerebellum of male and female rats revealed that the expression of these genes is developmentally regulated, with the highest levels at early postnatal ages in both sexes and with significantly higher mRNA levels in postnatal males. Expression of these genes in the female remained unaltered after perinatal androgenization and along the estrous cycle. In contrast, damage of cerebellar afferent neurons of the inferior olivary nucleus evoked a significant increase in StAR, P450scc, and aromatase mRNA levels at this site, as well as a transient elevation in StAR mRNA at the cerebellum. Finally, enhancement of cAMP levels in cultured cerebellar neurons induced a significant increase in StAR and aromatase mRNA levels. In summary, we present herein novel evidence for the developmentally regulated and partially sexually dimorphic pattern of expression of StAR, P450scc, and aromatase genes in the rat cerebellum. These observations, together with the finding that the mRNA levels of these steroidogenic molecules are sensitive to injury and are regulated by intracellular cAMP, strongly suggest that local steroidogenesis is likely to play an important role during development and adaptation to neurodegenerative processes in the olivocerebellar system.


Earlier intervention for acute kidney injury: evaluation of an outreach service and a long-term follow-up.
There have been few studies of earlier systematic intervention to reduce the impact of acute kidney injury (AKI). In 2009, we piloted an AKI outreach service with a before and after study, and we report on the study and its longer-term follow-up. AKI patients were identified using a laboratory delta check for creatinine of 75%. In the 4-week before phase patients received standard care. In a consecutive 7-week after phase an outreach team of nephrology doctors and nurses reviewed all alerts twice daily, 5 days a week. The primary clinical team caring for the patient was called to be given advice on AKI care. There were 157 and 251 patients in the before and after groups, respectively, who were comparable in their characteristics. The mean age was 70 years in both groups and ∼ 80% of each group were admitted to the hospital. In the after group, the Outreach telephone call was successful in 88%, at a median of 14 h. Substantial numbers of recommendations were made, largely related to fluid balance, investigations and medication use. Survival showed an immediate non-significant improvement in the after group, but converged at about 4 years. Outreach shows potential to improve outcomes in AKI. In order to achieve this it seems likely that at least a five-day per week service will be needed to assist good renal and general medical care for this vulnerable group.


Genistein: A Review on its Anti-Inflammatory Properties.
Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy. Genistein belongs to the flavonoid family, in the subgroup of isoflavones. It is a phytoestrogen that is mainly derived from legumes. It is a naturally occurring chemical constituent with a similar chemical structure to mammalian estrogens. It is claimed to exert many beneficial effects on health, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties. In the past, numerous in vitro and in vivo studies have been conducted to investigate the anti-inflammatory potential of genistein. Henceforth, this review aims to summarize the anti-inflammatory properties of genistein linking with the signaling pathways and mediators that are involved in the inflammatory response as well as its toxicity profile. The current outcomes are analysed to highlight the prospect as a lead compound for drug discovery. Data was collected using PubMed, ScienceDirect, SpringerLink and Scopus databases. Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokines and reactive oxygen species (ROS). A comprehensive assessment of the mechanism of action in anti-inflammatory effects of genistein is included. However, evidence for the pharmacological effects is still lacking. Further studies using various animal models to assess pharmacological effects such as toxicity, pharmacokinetics, pharmacodynamics, and bioavailability studies are required before clinical studies can be conducted. This review will highlight the potential use of genistein as a lead compound for future drug development as an anti-inflammatory agent.


Concurrent overactivation of the cytosolic glutamine synthetase and the GABA shunt in the ABA-deficient sitiens mutant of tomato leads to resistance against Botrytis cinerea.
Deficiency of abscisic acid (ABA) in the sitiens mutant of tomato (Solanum lycopersicum) culminates in increased resistance to Botrytis cinerea through a rapid epidermal hypersensitive response (HR) and associated phenylpropanoid pathway-derived cell wall fortifications. This study focused on understanding the role of primary carbon : nitrogen (C : N) metabolism in the resistance response of sitiens to B. cinerea. How alterations in C : N metabolism are linked with the HR-mediated epidermal arrest of the pathogen has been also investigated. Temporal alterations in the γ-aminobutyric acid (GABA) shunt, glutamine synthetase/glutamate synthase (GS/GOGAT) cycle and phenylpropanoid pathway were transcriptionally, enzymatically and metabolically monitored in both wild-type and sitiens plants. Virus-induced gene silencing, microscopic analyses and pharmacological assays were used to further confirm the data. Our results on the sitiens-B. cinerea interaction favor a model in which cell viability in the cells surrounding the invaded tissue is maintained by a constant replenishment of the tricarboxylic acid (TCA) cycle through overactivation of the GS/GOGAT cycle and the GABA shunt, resulting in resistance through both tightly controlling the defense-associated HR and slowing down the pathogen-induced senescence. Collectively, this study shows that maintaining cell viability via alterations in host C : N metabolism plays a vital role in the resistance response against necrotrophic pathogens.


In vivo magnetic resonance imaging tracking of transplanted superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells in rats with myocardial infarction.
Superparamagnetic iron oxide (SPIO) nanoparticles generate superparamagnetism, thereby resulting in an inhomogeneous local magnetic field, which shortens the T2 value on magnetic resonance imaging (MRI). The purpose of the present study was to use MRI to track bone marrow mesenchymal stem cells (BMSCs) labeled with SPIO in a rat model of myocardial infarction. The BMSCs were isolated from rats and labeled with SPIO. The anterior descending branch of the coronary artery was ligated under anesthesia. Two weeks later, the rats received, at random, 5 x 10(7) SPIO-labeled BMSCs, 5 x 10(7) unlabeled BMSCs or a vehicle (100 µl phosphate-buffered saline) via direct injection into the ischemic area (20 animals/group). MRI was used to track the SPIO‑labeled BMSCs and the rats were then sacrificed to verify the presence of BMSCs using immunohistochemistry with an anti-CD90 antibody. The procedure labeled 99% of the BMSCs with SPIO, which exhibited low-intensity signals on T2 and T2* MRI imaging. At 24 h post-BMSC transplantation, low-intensity MRI signals were detected on the T2 and T2* sequences at the infarction margins. After 3 weeks following transplantation, low-intensity signals started to appear within the infarcted area; however, the signal intensity subsequently decreased and became indistinct. Immunohistochemistry revealed that the SPIO-labeled BMSCs migrated from the margin into the infarcted region. In conclusion, the BMSCs were readily labeled with SPIO and in vivo and MRI tracking demonstrated that the SPIO-labeled BMSCs established and grew in the infarcted myocardium.


Short- and long-term follow-up after coronary bypass grafting for single-vessel coronary artery disease.
Short-term outcome and 10-year clinical outcome were reviewed in 114 consecutive patients after coronary artery bypass grafting (CABG) for single-vessel coronary artery disease (CAD). Gated equilibrium radionuclide cineangiography was performed soon after CABG in all cases, and revealed very good early graft patency rates. There was no perioperative mortality, and very low morbidity. During follow-up there were seven late deaths, two from cardiac disease and five from non-cardiac causes. Cumulative survival at 10 years was 93%. Cumulative freedom from additional cardiac invasive procedures was 96%, 93% and 80% at 1, 5, and 10 years, respectively, and cumulative freedom from angina was 93%, 80% and 73%. Conventional single-vessel CABG thus can be safely performed, with minimal postoperative morbidity and no mortality, providing good long-term relief of angina and circumventing need for additional invasive procedures.


Developing healthy weight maintenance through co-creation: a partnership with Black African migrant community in East Midlands.
Obesity prevalence in the UK varies according to ethnicity, with children from minority ethnic groups experiencing higher levels, and yet, there is a scarcity of projects that involve minority ethnic groups in the design of interventions to promote healthy weight maintenance. This article presents an account of the involvement of the participants in a co-creation activity to design public health resources for the maintenance of healthy weight. The material is drawn from a study that involved Black African parents (n = 30) and Health Visitors (n = 32), residing and working in the East Midlands, UK, respectively. The participants were purposely selected according to an inclusion/exclusion criterion and invited to participate in seven focus groups (FG) conducted for parents (FG-4) and health visitors (FG-3) at a time and place convenient to the participants. Following the focus groups, the Black African parents participated in three co-creation workshops. The co-creation activities involved the participants, the researcher and a nutritionist. The outcome was an African heritage eatwell guide and a framework to promote healthy weight, which was well-received when presented to members of the community and local health and social care practitioners. The co-creation process went beyond giving the participant a voice in shaping the promotion of healthy weight within their community, as they also became active participants in the design and creation of the specific public health service. The approach offered the potential for improved levels of community satisfaction for a public health intervention.


In-vivo platelet activation correlates with red cell anionic phospholipid exposure in patients with beta-thalassaemia major.
Several clinical and laboratory findings suggest the presence of a chronic hypercoagulable state in patients with beta-thalassaemia major (TM). We have previously shown that isolated TM red blood cells (RBC) strongly enhance prothrombin activation, suggesting an increased membrane exposure of procoagulant phospholipids (i.e. phosphatidylserine). In this study we quantitated the procoagulant activity of RBC in TM and thalassaemia intermedia (TI) patients. We also determined the fraction of activated platelets expressing p-selectin (CD62p) or CD63 in these subjects. Both assays were performed by dual-colour flow cytometry. A significantly (P < 0.01) higher fraction of FITC-annexin V-labelled RBC was found in TM and TI patients, compared to the controls. A highly significant correlation (P < 0.001) was found in TM patients between the number of RBC-bound annexin V molecules and the fraction of CD62p (p-selectin) or CD63-positive platelets. This association between annexin V binding to TM RBC and the expression of platelet activation markers was also found in individual TM patients over time. Thus, the procoagulant surface of TM RBC may accelerate thrombin generation in vivo which, in turn, triggers platelet activation.


COVID-19 and diabetes-Two giants colliding: From pathophysiology to management.
Since December 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread around the world, causing the coronavirus 2019 (COVID-19) pandemic. From the beginning, SARS-CoV-2 has put a strain on the health system. In fact, many patients have had severe forms of the disease with the need for hospitalization due to respiratory failure. To contain the pandemic, the most widely used approach has been lockdowns. Social restrictions have been reduced thanks to the development of vaccines and targeted therapies. However, fatal events still occur among people at high risk of serious infection, such as patients with concomitant diabetes. Different mechanisms have been proposed to explain the poor prognosis of patients with diabetes and COVID-19, but the specific cause is unclear. It is now known that insulin resistance, inflammation, and cytokine storm are involved. Moreover, SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptors to enter cells. This receptor is expressed on pancreatic beta cells and, during infection, it appears that receptor involvement may induce hyperglycemia in patients with or without diabetes. In this study, we discuss the mechanisms underlying the poor prognosis in people with COVID-19 and diabetes and what may improve the outcome in these patients.


The Role of Perceived Sleep Quality in Cardiovascular Health Factors and Behaviors Among Young Adults With Type 1 Diabetes.
The purpose of this study was to determine the associations between perceived sleep quality and individual cardiovascular health (CVH) factors (A1C and body mass index [BMI]) and CVH behaviors (physical activity and dietary diabetes self-management) in young adults ages 18 to 25 years with type 1 diabetes (T1D). Associations among perceived sleep quality and CVH factors and behaviors were examined using multivariable linear regression in 69 participants ages 18 to 25 years (mean age 21.4 ± 2.0, mean T1D duration 9.7 ± 5.6 years). Lower perceived sleep quality was associated with multiple lower CVH factors and behaviors (higher A1C and BMI, lower physical activity, poorer diet) even after adjusting for covariates (age, T1D duration, sex assigned at birth). Experimental studies are needed to better understand the impact of modifying sleep habits on both short- and long-term CVH in adults with T1D.


Fabrication and characterization of a novel crosslinked human keratin-alginate sponge.
Human hair keratins have been explored for biomedical applications because of their abundance, bioactivity and processability. However, pure keratin templates have poor mechanical properties, which limit their practical relevance. Herein, we described a novel composite sponge, consisting of human hair keratins chemically crosslinked with alginate using 1-ethyl-3-dimethylaminopropyl carbodiimide hydrochloride, with improved mechanical properties. Fourier transform infrared spectroscopy (FTIR) and free amine group quantification using ninhydrin revealed a maximum crosslinking index of 82.1 ± 1.3%. With increasing alginate proportions, the sponges exhibited increased tensile strength, tensile modulus and compression modulus at maximum values of 10.3 ± 1.92 kPa, 219.07 ± 52.39 kPa and 191.48 ± 32.89 kPa, respectively. The crosslinked sponges also demonstrated water vapour transmission rates comparable to commercial wound dressings. Meanwhile, sponges with higher proportions of keratin showed lower water uptake capacities and higher degradation rates by proteinase K, in comparison with sponges with higher proportions of alginate. Higher proportions of keratin on coated two-dimensional surfaces and in three-dimensional sponges resulted in more attachment and improved proliferation of L929 fibroblasts, verifying the bioactive role of keratin in the composites. In addition, subcutaneous implantation of the keratin-alginate sponges into C57BL/6NTac mice over 4 weeks showed no significant immunological reaction and minimal formation of fibrotic capsules. Furthermore, the sponges supported cellular infiltration, neo-tissue formation and vascularization in vivo. These findings demonstrated the feasibility of producing crosslinked human hair keratin-alginate sponges, with tuneable physical and mechanical properties, which are cell compliant in vitro and biocompatible in vivo, suggesting their potential for clinically relevant exploitations. Copyright © 2016 John Wiley & Sons, Ltd.