Placental and intra-amniotic inflammation are associated with altered fetal immune responses at birth.
High-grade placental inflammation is associated with preterm birth and poor neonatal outcomes. Recent reports suggest that low-grade placental inflammation is common in uncomplicated pregnancies. The relationship between placental inflammation and innate immune anti-microbial responses is unknown. In this study we sought to identify any association between placental inflammation and fetal immune responses. Cord blood samples collected from late preterm and full-term Caesarean section deliveries (n = 44) were exposed to various immune challenges (resiquimod, LPS, PGN, poly (I:C), cGAMP, and 5'ppp-dsRNA) and production of inflammatory mediators (G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α) was measured by multiplex assay. Hospital histology reports were used to assess the extent of inflammation in the placenta. Almost half (47.7%) of placentae examined here showed histological evidence of inflammation. Resiquimod, LPS, and PGN elicited strong inflammatory responses in neonatal cord blood, while poly (I:C), cGAMP, and 5'ppp-dsRNA elicited weaker responses. Fetuses with evidence of chorioamnionitis and fetal inflammatory reaction in their placentae had significantly increased immune responses to cGAMP and 5'ppp-dsRNA (ligands for STING and RIG-I, respectively) and significantly decreased immune responses to poly (I:C) (a TLR3 agonist). Interestingly, STING, RIG-I, and TLR3 are all involved in viral response pathways, suggesting that fetuses exposed to chorioamnionitis or fetal inflammatory reaction might respond differently to viruses postnatally. Our data suggest that low-level placental inflammation is associated with altered innate cytokine responses at birth.


Assessment of relative fertility of males (cockerels and boars) by competitive mating.
When hens were inseminated with an equal number of spermatozoa from one of 3 Leghorn (L) and one of 3 Columbian (C) cocks in the 9 possible L and C combination, a hierarchy of fertility was established based on the proportion of chicks sired by each cock. A similar hierarchy was established for 3 Duroc (D) and 3 Yorkshire (Y) boars by mating gilts in rapid succession to one D and one Y boar. A second hierarchy of fertility was established by inseminating hens with 40 x 10(6) spermatozoa from only one cock or by mating gilts to only one of the boars. The hierarchies for the cocks and boars were essentially the same for each method. Minor discrepancies were observed for males which appeared to be nearly equally fertile when used alone or in combination with another male. After homospermic insemination, the hierarchy of cocks was identical whether the ranking was based on the percentage of eggs fertilized or on hatchability of fertilized eggs. Similarly, the boars ranked highest in fertility by double mating had higher conception rates, higher embryonic survival rates and larger litter sizes when used alone. Heterospermic insemination and double mating appear to be more efficient and sensitive than methods of estimating fertility which depend on homospermic insemination of high or low numbers of spermatozoa, single matings or the examination of various characteristics of semen. The method of heterospermic insemination or double mating offers a simple and effective method of assessing the relative fertility of males.


A new paradigm to understand and treat diabetic neuropathy.
The clinical symptoms of diabetic neuropathy (DN) manifest in a time dependent manner as a positive symptoms (i. e. pain, hypersensitivity, tingling, cramps, cold feet etc.) during its early stages and by a loss of function (i. e. loss of sensory perception, delayed wound healing etc.) predominating in the later stages. Elevated blood glucose alone cannot explain the development and progression of DN and the lowering of blood glucose is insufficient in preventing and/or reversing neuropathy in patients with type 2 diabetes. Recently it has been shown that the endogenous reactive metabolite methylglyoxal (MG) can contribute to the gain of function via post-translational modification in DN of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. Dicarbonyls, such as MG, that are elevated in diabetic patients, modify DNA as well as extra- and intracellular proteins, leading to the formation of advanced glycation endproducts (AGEs). Increased formation of AGEs leads to increased cellular stress, dysfunction and ultimately cell death. The interaction of AGE-modified proteins through cell surface receptors, such as RAGE, can lead to increased cellular activation and sustained inflammatory responses, which are the molecular hallmarks of the later, degenerative, stages of DN. The direct and indirect effects of dicarbonyls on nerves or neuronal microvascular network provides a unifying mechanism for the development and progression of DN. Targeting the accumulation of MG and/or prevention of RAGE interactions may therefore provide new, more effective, therapeutic approaches for the treatment of DN.


Mechanistic Studies of the Inhibition of Insulin Fibril Formation by Rosmarinic Acid.
The self-assembly of insulin to form amyloid fibrils has been widely studied because it is a significant problem in the medical management of diabetes and is an important model system for the investigation of amyloid formation and its inhibition. A few inhibitors of insulin fibrillation have been identified with potencies that could be higher. Knowledge of how these work at the molecular level is not known but important for the development of more potent inhibitors. Here we show that rosmarinic acid completely inhibits amyloid formation by dimeric insulin at pH 2 and 60 °C. In contrast to other polyphenols, rosmarinic acid is soluble in water and does not degrade at elevated temperatures, and thus we were able to decipher the mechanism of inhibition by a combination of solution-state 1H NMR spectroscopy and molecular docking. On the basis of 1H chemical shift perturbations, intermolecular nuclear Overhauser effect enhancements between rosmarinic acid and specific residues of insulin, and slowed dynamics of rosmarinic acid in the presence of insulin, we show that rosmarinic acid binds to a pocket found on the surface of each insulin monomer. This results in the formation of a mixed tetramolecular aromatic network on the surface of insulin dimer, resulting in increased resistance of the amyloidogenic protein to thermal unfolding. This finding opens new avenues for the design of potent inhibitors of amyloid formation and provides strong experimental evidence for the role of surface aromatic clusters in increasing the thermal stability of proteins.


[Malignant lymphoma displaying rearrangements of both immunoglobulin and T-cell receptor genes].
A 65-year-old male was admitted to our hospital due to recurred malignant lymphoma of left tonsil origin. Studies using flow cytometry on mononuclear cells in peripheral blood revealed the appearance of intermediate B cells, and examinations on gastrointestinal tract showed diffuse infiltration of medium-sized lymphoid cells into stomach and colon, that had the same phenotype as tumor cells in peripheral blood. They suggested leukemic change and gastrointestinal tract infiltration of malignant lymphoma. Southern blot analysis revealed T-cell receptor beta-chain gene rearrangement as well as immunoglobulin gene rearrangement. Analysis by histo in situ hybridization on infiltrated gastric mucosa specimen showed diffuse expression of immunoglobulin mRNA in tumor cells, but no message of T-cell receptor beta-chain gene. Northern blot analysis showed the same result. It suggests that in this case, the rearrangement of T-cell receptor beta-chain gene is ineffective rearrangement without transcription to mRNA.


Endometriosis of the round ligament: description of a clinical case and review of the literature.
We report a case of endometriosis of the round ligament in a 29-year-old woman, who complained of a lump with a diameter of about 2.5 cm in the right inguinal region, which increased in bulk and was accompanied by intense pain during the menstrual period. The clinical suspicion of inguinal endometriosis, supported by ultrasonography and Magnetic Resonance (MR), was confirmed by histological examination of the surgical specimen, which included the mass and the extraperitoneal segment of the round ligament. The authors conclude that the appearance of a lump in the inguinal region associated with subjective and objective changes of the lesion in relation to the menstrual cycle must raise the suspicion of endometriosis among the possible diagnoses.


Insights into the Noncoding RNA-encoded Peptides.
Considerable evidence has indicated that most noncoding RNA (ncRNA) transcripts act directly as functional RNAs rather than as encoded peptides. However, a recent study of ribosome occupancy reported that many large intergenic ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are translated into proteins. These lincRNAs contain either Internal Ribosomal Entry Sites (IRES) or short Open Reading Frames (sORFs), and other translation elements, which can be translated into peptides with physiological functions. This review discusses three major types of ncRNA-encoded peptides (ncPEPs). First, microRNA(miRNA)-encoded peptides (miPEPs) are translated from their primary transcripts of miRNA genes and can promote the development of plant roots. Second, a long ncRNA(lncRNA) containing sORF encodes a 90 residues long regulatory peptide. Upon the amino acid response, the lncRNA-encoded peptide reduces the activity of mammalian Target Rapamycin complex 1 (mTORC1) and promotes muscle regeneration. Third, a circular RNA (circRNA) of the Na+/Ca2+ exchanger gene 1 (NCX1) exon 2 transcript encodes a truncated NCX1 protein exhibiting the Na+/Ca2+ exchange activity. It is also of worth noting that the majority of ncRNAs is not translated. This review summarizes the current understanding of the translatability of ncRNAs and the functions of ncPEPs in cellular processes, which may provide novel insights into the roles of ncPEPs.


Effects of large dose vitamin E supplementation on anemia in hemodialysis patients.
In order to clarify the effect of vitamin E (alpha-tocopherol) on anemia and the osmotic fragility of red blood cells (RBC) plasma and RBC levels of vitamin E were measured in 30 regular dialysis patients before and after oral supplementation of vitamin E, 600 mg daily for 30 days. Plasma levels of vitamin E were in the normal range (10.67 +/- 0.85, 9.73 +/- 0.77 microgram/ml) but RBC levels in packed red cells were significantly lower than healthy controls (0.57 +/- 0.05, 0.45 +/- 0.07 microgram/ml). Oral supplementation of vitamin E increased both plasma (20.37 +/- 1.61 micrograms/ml) and RBC vitamin E (1.56 +/- 0.11 micrograms/ml) in packed red cells, while in unsupplemented patients, vitamin E levels remained unchanged. In patients receiving vitamin E, mean osmolarities at the beginning and end of hemolysis decreased from 102.8 +/- 0.9 to 98.9 +/- 0.7 and 72.1 +/- 1.1 to 67.4 +/- 0.8 mosm/l, respectively. In addition, the hematocrit increased from 26.1 +/- 1.0 to 28.1 +/- 1.2%. These changes are statistically significant (less than 0.05). In conclusion, the oral supplementation of vitamin E could be of clinical benefit in correcting anemia in regular dialysis patients by reducing the fragility of RBCs.


[Analysis of the correlation between hydrophilic-lipophilic balance, coefficient of diffusion and hydrogen ion concentration in a series of nonsteroidal anti-inflammatory drugs].
A thorough investigation on the dependence of rate diffusion constants (Kd) of nonsteroidal antiinflammatory drugs on pH and pKa values was carried out. It is shown that a modified multiparametric curve-fitting technique may constitute an useful tool to describe the rate diffusion pH-profiles of ionogenic substances. A comparison between the Kd values and the corresponding distribution coefficients (log D) shows that these constants identify complementary parameters very useful in the study of structure-activity relationships of ionogenic substances.


Laparoscopic inferior and superior lumbar hernia repair.
Lumbar hernias are rare defects that involve the extrusion of retroperitoneal fat or viscera through a weakness in the posterior abdominal wall. Repairing these hernias is often difficult because of the weakness of the surrounding structures. Techniques for reconstruction usually include an incision from the 12th rib to the iliac crest with mobilization of local flaps or onlay fascial flaps or the use of prosthetic mesh. Contemporary reports have advocated extensive retroperitoneal dissection with the placement of permanent mesh extraperitoneally. We have recently repaired an extensive, primary lumbar hernia laparoscopically, securing the mesh to the 12th rib superiorly, iliac crest inferiorly, erector spinae fascia medially, and external oblique fascia laterally. The patient resumed normal activities in less than 2 weeks; 4 months postoperatively, he seems to have a solid repair. To our knowledge, this is the first report of this technique.


A family of candidate taste receptors in human and mouse.
The gustatory system of mammals can sense four basic taste qualities, bitter, sweet, salty and sour, as well as umami, the taste of glutamate. Previous studies suggested that the detection of bitter and sweet tastants by taste receptor cells in the mouth is likely to involve G-protein-coupled receptors. Although two putative G-protein-coupled bitter/sweet taste receptors have been identified, the chemical diversity of bitter and sweet compounds leads one to expect that there is a larger number of different receptors. Here we report the identification of a family of candidate taste receptors (the TRBs) that are members of the G-protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells. A cluster of genes encoding human TRBs is located adjacent to a Prp gene locus, which in mouse is tightly linked to the SOA genetic locus that is involved in detecting the bitter compound sucrose octaacetate. Another TRB gene is found on a human contig assigned to chromosome 5p15, the location of a genetic locus (PROP) that controls the detection of the bitter compound 6-n-propyl-2-thiouracil in humans.


Proteomic analysis of plasma in the polycystic ovary syndrome identifies novel markers involved in iron metabolism, acute-phase response, and inflammation.
Hypothesis-free approaches such as proteomic analysis may identify novel biomarkers for disease. The objective of the study was to compare the plasma proteome of patients presenting with the polycystic ovary syndrome (PCOS) with that of women without hyperandrogenism. This was a case-control study. The study was conducted at an academic hospital. Patients included 12 PCOS patients and 12 women without hyperandrogenism. Interventions included basal blood sampling. Two-dimensional difference in-gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, Western blot, and ELISA analyses were measured. Two-dimensional difference in-gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analyses identified haptoglobin beta-chain and alpha2-macroglobulin as proteins underexpressed in PCOS samples, whereas transferrin and kappa-free light chain were overexpressed. We were able to confirm only the underexpression of haptoglobin beta-chain in subsequent Western blot and ELISA analyses. Proteomic analysis of plasma from PCOS patients revealed changes in protein expression in several acute-phase response proteins including isoforms of plasma haptoglobin, alpha2-macroglobulin, and transferrin and in kappa-free light chain. In addition to their role as inflammatory markers, some of these molecules play major roles in iron metabolism, further suggesting that iron metabolism and low-grade chronic inflammation may be involved in the pathogenesis of insulin-resistant disorders such as PCOS.


Inverse relationship between raft LRP1 localization and non-raft ERK1,2/MMP9 activation in idiopathic dilated cardiomyopathy: potential impact in ventricular remodeling.
Idiopathic dilated cardiomyopathy (IDCM) is characterized by adverse ventricular remodeling attributed to altered activity of extracellular matrix metalloproteinase (MMP). MMP overactivation is linked to changes in extracellular signal-regulated kinases (ERK), reportedly modulated by the low-density lipoprotein receptor-related protein 1 (LRP1) receptor. The aim of this work was to compare the levels, membrane distribution and interactions of LRP1, ERK1,2 and MMP2/9 in control and IDCM myocardium. Left ventricle samples from IDCM patients and control subjects were collected to analyze gene and protein expression by Real-time PCR and Western blot, respectively. Fractions enriched in cholesterol, Flotillin-1 and Caveolin-3 (rafts) were isolated from the remaining membrane (non-rafts) by sucrose gradient ultracentrifugation. We assessed the formation of LRP1-ERK1,2 complexes and MMP activity by immunoprecipitation and zymography, respectively. In control myocardium, LRP1 was exclusively found in non-rafts while activation of ERK1,2 was preferentially detected in rafts. LRP1/p-ERK1,2 complexes were almost undetectable in rafts and non-rafts. In contrast, in IDCM myocardium, LRP1 moved to rafts and ERK1,2 activation was found in raft and non-raft fractions. Moreover, LRP1/p-ERK1,2 complexes were also found in both membrane fractions, although the amount was higher in non-rafts where MMP9 overactivation was exclusively detected. The presented findings demonstrate a differential membrane compartmentalisation of ERK signaling in IDCM myocardium. The movement of LRP1 to rafts and the concomitant increase in non-raft-related ERK1,2/MMP9 activation may have crucial clinical implications in the progression of disease.


Recent Advances in Chemical Tools for the Regulation and Study of Protein Lysine Methyltransferases.
Protein lysine methyltransferases (PKMTs) are epigenetic regulators that modulate gene transcription and physiological functions by catalyzing the post-translational methylation of specific lysine residues of substrate proteins, such as histones. They are considered to be candidate drugs for the treatment of various diseases, including acute myeloid leukemia, and in the past decade, potent and selective inhibitors of individual PKMTs have been developed. Some are currently under clinical trial. In this review, we will focus on some breakthrough PKMT inhibitors, and discuss chemistry-based methods available for elucidation of the physiological functions of PKMTs and methylated proteins.


Effects of inhaled diesel emissions and coal dust in rats.
Rats were exposed to coal dust and diesel exhaust emissions, separately and in combination, for 20 months to evaluate the potential health effects of these specific mine air materials. The diesel exhaust was produced by an engine operated in a load, no-load mode and acceleration, deceleration cycle. It was also modified to simulate an inefficiently tuned engine. Exposure to coal dust was performed in a whole-body rodent inhalation system. Mortality, body weight and hematologic parameters examined were normal compared with those of control rats. Lesions observed were primarily restricted to the lungs and were similar to those described for simple coal workers' pneumoconiosis (CWP). Lesion progression and severity was related to exposure duration and exposure material. Alveolar bronchiolization, though not reported in human CWP, was present in the lungs of some rats in all exposure groups except the control animals.


Single bouts of exercise affect albumin redox state and carbonyl groups on plasma protein of trained men in a workload-dependent manner.
The purpose of this study was to investigate the effect of single bouts of exercise at three different intensities on the redox state of human serum albumin (HSA) and on carbonyl groups on protein (CP) concentrations in plasma. Trained men [n = 44, maximal oxygen consumption (Vo(2max)): 55 +/- 5 ml.kg(-1).min(-1), nonsmokers, 34 +/- 5 years of age] from a homogenous population, volunteers from a police special forces unit, were randomly assigned to perform on a cycle ergometer either at 70% (n = 14), 75% (n = 14), or 80% (n = 16) of Vo(2max) for 40 min. Blood was collected before exercise, immediately after the exercise test (IE), and 30 min after each test (30M) and 30 h after each test (30H). The reduced fraction of HSA, human mercaptalbumin (HMA), decreased at all three exercise intensities IE and 30M, returning to preexercise values by 30H (P < 0.05). HMA was primarily oxidized to its reversible fraction human nonmercaptalbumin 1 (HNA1). CP concentrations increased at 75% of Vo(2max) IE and 30M with a tendency (P < 0.1) and at 80% Vo(2max) IE and 30M significantly, returning to preexercise concentrations by 30H (P < 0.01). These results indicate that the HSA redox system in plasma is activated after a single bout of cycle ergometer exercise at 70% Vo(2max) and 40 min duration. The extent of the HSA modification increased with exercise intensity. Oxidative protein damage, as indicated by CP, was only significantly increased at 80% Vo(2max) intensity in this homogenous cohort of trained men.


Platelet and von Willebrand factor interactions at the vessel wall.
The process of platelet thrombus formation contributes to the haemostatic response that prevents excessive blood loss after tissue injury, but may become a life-threatening disease mechanism by causing the acute thrombotic occlusion of atherosclerotic arteries. The participation of platelets in the formation of thrombi is centered on their adhesive properties and the ability to respond to stimuli with rapid activation. Platelet adhesion and activation are multifaceted and modulated by different environmental conditions, suggesting that it should be possible to obtain a selective pharmacological inhibition of the pathways more relevant to athero-thrombosis than to haemostasis. In particular, progress in understanding the structure and function of von Willebrand factor and the mechanisms that underlie its interactions with vascular surfaces and platelets can elucidate important differentiating aspects of normal haemostasis and pathological arterial thrombosis.


Determination of Fentanyl Analog Exposure Using Dried Blood Spots with LC-MS-MS.
Fentanyl, and the numerous drugs derived from it, are contributing to the opioid overdose epidemic currently underway in the USA. To identify human exposure to these growing public health threats, an LC-MS-MS method for 5 μL dried blood spots (DBS) was developed. This method was developed to detect exposure to 3-methylfentanyl, alfentanil, α-methylfentanyl, carfentanil, fentanyl, lofentanil, sufentanil, norcarfentanil, norfentanyl, norlofentanil, norsufentanil, and using a separate LC-MS-MS injection, cyclopropylfentanyl, acrylfentanyl, 2-furanylfentanyl, isobutyrylfentanyl, ocfentanil and methoxyacetylfentanyl. Preparation of materials into groups of compounds was used to accommodate an ever increasing need to incorporate newly identified fentanyls. This protocol was validated within a linear range of 1.00-100 ng/mL, with precision ≤12% CV and accuracy ≥93%, as reported for the pooled blood QC samples, and limits of detection as low as 0.10 ng/mL. The use of DBS to assess fentanyl analog exposures can facilitate rapid sample collection, transport, and preparation for analysis that could enhance surveillance and response efforts in the ongoing opioid overdose epidemic.


Lipopolysaccharide-induced murine B cell proliferation: a role of protein kinase C.
Lipopolysaccharide (LPS)-induced murine B cell proliferation was blocked by 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine dihydrochloride (H7), an inhibitor of protein kinase C (PKC), in a dose- and time-dependent manner. The maximum inhibition of B cell proliferation was observed when H7 was added at the initiation of cultures. H7-induced inhibition was prolonged and irreversible. Furthermore, pretreatment of B cells with phorbol myristate acetate ester, a process that degrades membrane-associated PKC, rendered them unresponsive to LPS. These data strongly suggest that the activation of PKC is one of the mechanisms of LPS-induced murine B cell proliferation.


Thickness of ice on perennially frozen lakes.
The dry valleys of southern Victoria Land, constituting the largest ice-free expanse in the Antarctic, contain numerous lakes whose perennial ice cover is the cause of some unique physical and biological properties. Although the depth, temperature and salinity of the liquid water varies considerably from lake to lake, the thickness of the ice cover is remarkably consistent, ranging from 3.5 to 6 m, which is determined primarily by the balance between conduction of energy out of the ice and the release of latent heat at the ice-water interface and is also affected by the transmission and absorption of sunlight. In the steady state, the release of latent heat at the ice bottom is controlled by ablation from the ice surface. Here we present a simple energy-balance model, using the measured ablation rate of 30 cm yr-1, which can explain the observed ice thickness.


Memory characteristics of a self-assembled monolayer of Pt nanoparticles as a charge trapping layer.
A self-assembled monolayer of Pt nanoparticles (NPs) was studied as a charge trapping layer for non-volatile memory (NVM) applications. Pt NPs with a narrow size distribution (diameter ∼4 nm) were synthesized via an alcohol reduction method. The monolayer of these Pt NPs was immobilized on a SiO(2) substrate using poly(4-vinylpyridine) (P4VP) as a surface modifier. A metal-oxide-semiconductor (MOS) type memory device with Pt NPs exhibits a relatively large memory window of 5.8 V under ± 7 V for program/erase voltage. These results indicate that the self-assembled Pt NPs can be utilized for NVM devices.


Clinical evidence of ozone interaction with pain mediators.
To address the clinical evidence that may support the fact that subcutaneous administration of ozone (O₃) has anti-hyperalgesic effects probably acting by modifying specific pain targets. Fifty-two patients attending the Medinat Clinic, Camerano, Ancona, Italy between October 2004 to October 2009 were eligible to participate in the study. Panoramic photos of painful and not painful areas submitted to oxygen (O₂)/O₃ ozone treatment injection were analyzed to detect the intensity of erythema. The erythematic areas after O₃ subcutaneous puncture showed significant (p<0.05) increment (83 ± 5%) in the painful area versus 7 ± 6% in the contralateral area. The surrounding erythema observed during O₃ intervention should explain at least in part, its interaction with some pain mediators. This may involve algesic mediators or receptors. The analgesic mechanism induced by O₂/O₃ may involve 2 independent steps: a short-term mechanism that may correspond with the direct oxidation on biomolecules, and a long-term mechanism that may involve the activation of antioxidant pathways. Further studies are needed to support the biochemical analgesic mechanism of O₃ therapy.


Impact of stent overlap on long-term clinical outcomes in patients treated with newer-generation drug-eluting stents.
Early-generation drug-eluting stent (DES) overlap (OL) is associated with impaired long-term clinical outcomes whereas the impact of OL with newer-generation DES is unknown. Our aim was to assess the impact of OL on long-term clinical outcomes among patients treated with newer-generation DES. We analysed the three-year clinical outcomes of 3,133 patients included in a prospective DES registry according to stent type (sirolimus-eluting stents [SES; N=1,532] versus everolimus-eluting stents [EES; N=1,601]), and the presence or absence of OL. The primary outcome was a composite of death, myocardial infarction (MI), and target vessel revascularisation (TVR). The primary endpoint was more common in patients with OL (25.1%) than in those with multiple DES without OL (20.8%, adj HR=1.46, 95% CI: 1.03-2.09) and patients with a single DES (18.8%, adj HR=1.74, 95% CI: 1.34-2.25, p<0.001) at three years. A stratified analysis by stent type showed a higher risk of the primary outcome in SES with OL (28.7%) compared to other SES groups (without OL: 22.6%, p=0.04; single DES: 17.6%, p<0.001), but not between EES with OL (22.3%) and other EES groups (without OL: 18.5%, p=0.30; single DES: 20.4%, p=0.20). DES overlap is associated with impaired clinical outcomes during long-term follow-up. Compared with SES, EES provide similar clinical outcomes irrespective of DES overlap status.


Solifenacin succinate for the treatment of symptoms of overactive bladder.
Overactivity of the bladder detrusor muscle can result in urinary urgency, frequency, and incontinence. Antimuscarinic agents are the treatment of choice, as they reduce the contractility of this muscle. Solifenacin succinate (SOL) is a competitive muscarinic-receptor antagonist approved by the US Food and Drug Administration in late 2004 for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. This article reviews the current primary literature concerning the pharmacokinetics, efficacy, and tolerability of SOL in the treatment of OAB. Pertinent English-language articles were identified through a search of MEDLINE (1966-week 4, 2006), EMBASE (1991-first quarter of 2006), Current Contents/Clinical Medicine (week 10, 2005-week 9, 2006), the Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, solifenacin, YM905, pharmacokinetics, and cost. SOL is highly lipophilic (50:1 octanol:water distribution at pH 7.0), completely orally bioavailable, and 98% protein bound. It is metabolized by the cytochrome P450 3A isozyme, and approximately 50% of a dose is eliminated renally as parent compound, with 1 active and 3 inactive metabolites. In two 12-week Phase III studies, patients receiving SOL 5 or 10 mg had significant reductions compared with placebo in the numbers of voids (P < or = 0.01), incontinence episodes (P < or = 0.05), and urgency episodes (P < or = 0.01) per 24 hours; the volume voided per micturition was significantly increased (P < or = 0.01). In a study that compared SOL 5 and 10 mg with tolterodine extended release 4 mg, both agents were associated with significant reductions in the number of voids per 24 hours (-2.45 and -2.24 episodes, respectively; P = 0.004 for noninferiority). In a study of pooled data from two 12-week studies, patients who received SOL 5 or 10 mg reported significant improvements in a number of quality-of-life domains (P < or = 0.05). In a pooled analysis of 4 studies, the most common adverse effects (occurring in > or =3% of any group) in patients receiving SOL 5 mg (n = 266) and 10 mg (n = 612) were dry mouth (10.9% and 27.1%, respectively), constipation (5.3% and 12.9%), and blurred vision (4.5% and 4.7%). In the studies reviewed, SOL was effective in the treatment of OAB with urge incontinence. Adverse effects included dry mouth, constipation, and blurred vision. Further studies are needed to determine the efficacy and tolerability of SOL in patients with hepatic or renal impairment.


A combinative effect of low-molecular-weight heparin and intermittent pneumatic compression device for thrombosis prevention during laparoscopic fundoplication.
BACKGROUND. Venous thromboembolism is known to be an important social and health care problem because of its high incidence among patients who undergo surgery. For instance, 20-30% of patients develop this problem after general surgical operations, while 5.5% of patients have this complication when laparoscopic fundoplications are performed without any prophylaxis. The aim of our study was to evaluate the hypocoagulation effect of the following treatments during and after laparoscopic fundoplication: a) intermittent pneumatic compression (IPC) and b) combination of low-molecular-weight heparin (LMWH) and IPC. MATERIAL AND METHODS. The study was performed on 20 consecutive patients who were randomized into two groups. The first group received IPC during operation, the second group received IPC during operation and LMWH before operation. Plasma prothrombin fragment F1+2 (F1+2), thrombin-antithrombin complex (TAT) - markers of thrombogenesis - and plasma free tissue factor pathway inhibitor (fTFPI) - a marker of hypocoagulation effect - were measured 1 h before, during, and after the laparoscopic operation. RESULTS. In the IPC group, plasma F1+2 and TAT levels increased significantly during and after laparoscopic gastrofundoplication. In the IPC+LMWH group, F1+2 and plasma TAT levels did not change during or after the operation. fTFPI levels significantly increased during and after the operation in the IPC+LMWH group; however, fTFPI levels did not change during or after the laparoscopic operation in the IPC group. CONCLUSIONS. A combination of low-molecular-weight heparin and intermittent pneumatic compression during laparoscopic fundoplication caused hypocoagulation effect in the patients, which was not observed in the patients who were treated with intermittent pneumatic compression alone.


A DNA-templated silver nanocluster probe for label-free, turn-on fluorescence-based screening of homo-adenine binding molecules.
A novel, label-free, turn-on fluorescence strategy to detect molecules that bind to adenine-rich DNA sequences has been developed. The probe employs DNA-templated silver nanoclusters (DNA-AgNCs) as the key detection component. The new strategy relies on the formation of non-Watson-Crick homo-adenine DNA duplex, triggered by strong interactions with homo-adenine binding molecules, which brings a guanine-rich sequence in one strand close to DNA-AgNCs located on the opposite strand. This phenomenon transforms weakly fluorescent AgNCs into highly emissive species that display bright red fluorescence. Finally, we have shown that the new fluorescence turn-on strategy can be employed to detect coralyne, the most representative homo-adenine binding molecule that triggers formation of a non-Watson-Crick homo-adenine DNA duplex.


Antiinflammatory activities of lactoferrin.
Lactoferrin is a non-heme iron binding glycoprotein produced during lactation and by epithelial cells at mucosal surfaces. The protein is a prominent component of the first line of mammalian host defense and its expression is upregulated in response to inflammatory stimuli. In this paper, the antibacterial and immune modulatory properties of lactoferrin that contribute to host defense are reviewed. In addition, the results of recent preclinical and clinical studies demonstrating that lactoferrin acts as an inhibitor of dermal inflammatory cytokine production are summarized. The results indicate that lactoferrin may act as a potent anti-inflammatory protein at local sites of inflammation including the respiratory and gastrointestinal tracts.


Caffeine: A novel green precursor for synthesis of magnetic CoFe2O4 nanoparticles and pH-sensitive magnetic alginate beads for drug delivery.
Hydrogel beads are promising delivery systems for encapsulation and release of drugs due to the mild process of their fabrication from biopolymers. Magnetic CoFe2O4 nanoparticles (MCFO, 9.72nm in diameter) were synthesized via a co-precipitation method using caffeine as a new environmentally friendly material in order to alkalinize the medium. Drug-targeting Magnetic beads based on CoFe2O4 nanoparticles, sodium alginate and chlorpheniramine maleate (CPAM) were synthesized in the presence of Ca2+ ions to obtain ionic cross-linked magnetic hydrogel beads. Nanoparticles as well as produced magnetic beads were thoroughly characterized by FTIR, XRD, SEM, nanosizer and VSM techniques. The swelling ratio of beads indicated pH-dependent property with maximum water absorbing at pH7.4. The in vitro release of beads exhibited significant behavior on the subject of nanoparticles concentration and alginate content. Biocompatibility of the CFO nanoparticles and MCFO/Alg beads are demonstrated through cytotoxicity test via MTT assay on U87 cell lines.


Metaplastic breast carcinoma on fine-needle cytology samples: a report of three cases.
Metaplastic breast carcinoma (MBC) may have a varied presentation on fine-needle cytology samples. We herewith describe three cases of MBC found in our series. One of these cases showed a peculiar mixture of malignant ductal, apocrine type, and squamous epithelial cells with fascicles of spindle cells with variable degree of atypia and was diagnosed as metaplastic carcinoma of the carcino-sarcomatous type. The other two lesions were characterized by an abundant chondroid extracellular matrix to which were variably admixed carcinomatous and chondroid-type cells, with variable degree of atypia. Both these latter cases were defined as matrix-producing metaplastic carcinomas. Because of the various presentation of MBC on fine-needle cytology samples and the possible influence of needle "sampling" on the cytological specimen, the spectrum of differential diagnoses to be considered may encompass a number of benign and malignant entities, like keratinous subareolar cysts, malignant fibroepithelial lesions with myxo-chondroid stroma, and true sarcomas of the breast, with cartilaginous metaplasia. It is the Authors' feeling that, with optimal samples, the cytomorphological findings of this rare variant of breast carcinoma permit its accurate pre-operative diagnosis.


Construction of a portal implantable functional tissue-engineered liver using perfusion-decellularized matrix and hepatocytes in rats.
Innovative cell-based therapies, including hepatic tissue engineering following hepatocyte transplantation, are considered as theoretical alternatives to liver transplant or for partial replacement of liver function in patients. However, recent progress in hepatic tissue engineering has been hampered by low initial hepatocyte engraftment and insufficient blood supply in vivo. We developed an intact 3D scaffold of an extracellular matrix (ECM) derived from a decellularized liver lobe, with layer-by-layer (LbL) heparin deposition to avoid thrombosis, which we repopulated with hepatocytes and successfully implanted as a tissue-engineered liver (TEL) into the portal system. The TEL provided sufficient volume for transplantation of cell numbers representing up to 10% of whole-liver equivalents and was perfused by portal vein blood. Treatment of extended hepatectomized rats with a TEL improved liver function and prolonged survival; mean lifespan was extended from 16 to 72 h. At 72 h postoperation, the TEL sustained functional and viable hepatocytes. In conclusion, we propose the TEL as a state-of-the-art substitute for whole-liver transplantation and as a proof of concept for the technology that will eventually allow for the transplantation of a reconstituted liver.


[A rare case of gastric outlet syndrome: internal incarceration after removal of gastric banding].
The laparoscopically administrated adjustable gastric banding used to be widely practiced as treatment of extreme obesity. As lots of complaints and complications arose sooner or later after this procedure, they had to be removed quite often. Half year after such a removal we observed a 37-year-old female patient with complete gastric outlet obstruction. The patient was operated and cured completely. The cause of gastric obstruction was an internal incarceration of the pyloric region between the plication made at the time of the ring removal and the gastric body. We found no similar case of gastric outlet obstruction in the corresponding literature.


Supervising trauma life support by telemedicine.
The resuscitation room in a community hospital was linked with a main hospital accident and emergency department using telemedicine equipment working at 384 kbit/s. Fifteen simulated casualties replicated the 'moulage' scenarios in the Advanced Trauma Life Support Course Manual of the American College of Surgeons. Each of the 15 scenarios was broken down into three main parts: the primary survey, resuscitation and the secondary survey. While a physician in the community hospital undertook each task, a senior doctor in the accident and emergency department recorded his degree of confidence in the supervision of the task on a five-point scale. There were features of the management which the supervisor found difficult, mainly related to the camera view and the use of a proxy examiner. However, supervising major trauma management by telemedicine was feasible. The average scores were mostly above 3 and often above 4 in the assessment of the primary survey and the resuscitation. The average scores were mostly above 3 for the secondary survey but were less often above 4 than for the primary survey and the resuscitation. Trials of remote trauma management with real patients appear to be justified.


Melting-profile analysis of thermal stability of thermolysin. A formulation of temperature-scanning kinetics.
The melting-profile method consists of a continuous observation of a structural parameter while the temperature of the sample is raised at a constant rate [Fugita, S. C., & Imahori, K. (1974) IN Peptides, Polypeptides and Proteins (Blout, E. R., Bovey, F. A., Goodman, M., & Lotan, N., Eds.) p 217, Wiley, New York, N.Y.]. An analytical solution to the melting profile was formulated for the two-state irreversible process and called temperature-scanning kinetics. The theory was tested with thermolysin with consistent results, and the thermodynamic parameters of thermal denaturation were calculated: deltaH identical to = 80.3 kcal/mol, deltaS identical to = 153 eu. These values agreed with the corresponding values obtained from the classical constant-temperature relaxation kinetics. The possibilities of temperature-scanning kinetics are discussed.


Salsolinol, an antagonist of prolactoliberine, induces an increase in plasma catecholamine levels in the rat.
It has been recently observed that salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a putative endogenous prolactin-releasing factor is a potent inhibitor of stress-induced release of epinephrine and norepinephrine. The prolactin release caused by salsolinol was inhibited by 1-methyl-3,4-dihydroisoquinoline (1MeDIQ). Therefore, the aim of our present studies was to investigate the effect of 1MeDIQ on plasma catecholamine levels. It has been found that 1MeDIQ is able to induce a massive increase in plasma catecholamine levels. Pretreatment of the animals with a ganglionic blocker, chlorisondamine, could completely abolish the effect of 1MeDIQ on plasma norepinephrine, and plasma epinephrine levels were only significantly attenuated. Spinal cord transection between cervical and thoracic segments eliminated 1MeDIQ induced increase in epinephrine, whereas increase in plasma norepinephrine was not affected. Hence, this effect of 1MeDIQ on sympathoadrenal system activity is most probably mediated through the level of sympathetic ganglia or partially at more centrally located sites of the nervous system. These results suggest that elevation of plasma catecholamines is involved in the mechanism of action of 1MeDIQ inhibiting the biological effect of salsolinol.


Relationship between cell kinetics and apoptotic effects in TNF-alpha and IFN-gamma-treated human tumour cell lines.
TNF-alpha is a potent inducer of apoptosis and also affects the transit of cells through the phases of the cell cycle. It is thought that the proliferation signalling pathway is related to the apoptosis pathway, the details of this cross-talk are not yet fully understood. In this report, the effects of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human tumour cell lines with respect to proliferation and apoptosis are examined. The TNF-alpha-sensitive cell lines Me-180 and MCF-7, the resistant cell line TCC-Sup, and the intermediate line 5637 were used. After a one day treatment, the transit through all phases of the cell cycle slowed down and after 3 days stopped completely, as measured with the BrdU-assay and flow cytometry. During the same time however, the levels of c-Myc and Ki-67 expression and the number of cells becoming apoptotic increased. Combined treatment with TNF-alpha and IFN-gamma augmented both the effects on the cell cycle and on apoptosis in the sensitive lines, and had only a minor additional effect on the resistant cell line as compared to single TNF-alpha treatment. The cells becoming apoptotic detached from the culture flask bottom and floated in the medium. Several apoptosis assays were used to prove that the floating cells were indeed apoptotic. As a subsidiary result of receptor measurement, we observed complexes of TNF-alpha receptors I with TNF-alpha receptors II using the related blocking antibodies and I125-TNF-alpha as ligand. The association of proliferative parameters and apoptosis became obvious by plotting the levels of c-Myc expression versus remaining live cells after apoptotic cells were detached. Our data revealed a good linear correlation indicating that high levels of c-Myc render cells sensitive to apoptosis, independent of the treatment, TNF-alpha alone or TNF-alpha in combination with IFN-gamma. The quantitative linear correlation may point to a threshold mechanism.


Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles.
A new nanoparticulate delivery system for amphotericin B (AmB) has been developed by means of the polyelectrolyte complexation technique. Two opposite charged polymers were used to form nanoparticles through electrostatic interaction, chitosan (CH) as a positively charged polymer and dextran sulfate (DS) as a polymer with a negative charge, together with zinc sulfate as a crosslinking and hardening agent. The AmB nanoparticles obtained possessed a mean particle size of 600-800 nm with a polydispersity index of 0.2, indicating a narrow size distribution. The measured zeta potential of the nanoparticle surface was approximately -32 mV indicating a strong negative charge at the particle's surface. Scanning electron microscopy revealed spherical particles with a smooth surface. Drug association efficacy of up to 65% was achieved. Dissolution studies demonstrated a fast release behavior suggesting that AmB exhibits only moderate interaction with the weakly crosslinked polymers of the nanoparticles. Although, electronic absorbance spectra showed that the aggregation state of AmB was modified within the nanoparticles, a reduction of nephrotoxicity was observed in an in vivo renal toxicity study.


The link between intravenous multiple pump flow errors and infusion system mechanical compliance.
IV drug delivery in intensive care often takes the form of simultaneous multiple infusions from separate infusion devices via either shared or individual fluid pathways. Because of the potency of the drugs administered and the acuity of the patients, accurate drug delivery is required. Instances of unexpected and unacceptable accuracy degradation have been reported when the equilibrium of the infusion system is disturbed. We describe a mathematical model of a simple infusion system used to investigate and verify results reported from a simple experimental multiple pump fault scenario. The results suggest that flow degradation is attributable to small changes in infusion system extracorporeal volume, referred to as "compliance." The model may, by expansion, be used to determine the nature of fluid flow within other multiple pump systems, be applied to the design of future IV systems, and explain the need for small-volume infusion systems with small mechanical compliance.


Ascending aorta, aortic arch and supra-aortic vessels rupture in blunt thoracic trauma.
Surgical strategy and long-term outcomes of patients with rupture of the ascending aorta, aortic arch and supra-aortic vessels following blunt thoracic trauma have been rarely reported. We reviewed our institutional experience between 1995 and 2016. We identified 2 patients with an innominate artery ruptures, 2 with an aortic arch ruptures and 1 with an ascending aorta rupture; all were induced by the posterior displacement of the anterior chest wall. All patients underwent open surgical repair. Cardiopulmonary bypass with antegrade cerebral perfusion was required in 2 cases. All patients were alive at the end of the follow-up (median 18 months; from 3 to 180 months) including 1 patient with cortical blindness.


[Evaluation of vaccination coverage rapid monitoring in the West Minas Gerais Extended Health Region, Brazil, 2012].
to evaluate the results of the Rapid Monitoring of the Coverage (RMC) of the childhood vaccination schedule in West Minas Gerais Extended Health Region, Brazil, in 2012. this was a descriptive study of RMC data available on the Unified Health System Information Department website; coverage of the childhood vaccination schedule was examined in 6 Health Micro-Regions. RMC involved 7,728 children aged between 6 months and 4 years and 11 months old; all micro-regions had at least one immunobiologic product with vaccination coverage below that recommended by the Ministry of Health; the most cited reason for non-vaccination was lack of time (21.2%); shortcomings were found in RMC records. in addition to low coverage, inconsistencies were found in RMC information. This points to the need to review RMC implementation and supervision, as well as RMC staff preparation and mobilization.


The impact of metabolic parameters on the change of pulmonary function in obese patients.
Ethnic differences exist in the function and distribution of adipose tissue, which influences whole body metabolism, including pulmonary function. The object of this study was to examine the relationships between serum metabolic parameters and pulmonary function in a morbidly obese Asia-Pacific population. One-hundred thirty-seven morbidly obese Chinese patients, aged≥18 years with a body mass index (BMI)>32 kg/m(2) who were being evaluated for bariatric surgery between July 2007 and December 2008, were studied. Cross-sectional associations between serum metabolic parameters, including lipids, glucose, insulin, leptin, and adiponectin levels with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁) assessed by spirometry, were analyzed. Multiple regression analyses also were conducted, with age, gender, smoking history, and various anthropometric measurements of obesity as confounders. Serum adiponectin and HDL cholesterol had a positive correlation with FVC and FEV1. In addition, insulin resistance, determined by the homeostatic model assessment method (HOMA), was negatively correlated with FVC. In the multiple linear regression analysis, only serum adiponectin was significantly correlated with FVC and FEV₁, independent of obesity level. Serum adiponectin level was positively and independently associated with pulmonary function in morbidly obese Chinese adults.


Effect of Kampo extracts on urinary stone formation: an experimental investigation.
To examine the effects of Kampo extracts on the process of urinary stone formation. A total of 14 Kampo extracts (10 μg/mL) were examined in vitro by assessing whether they could inhibit two critical steps in the early process of calcium oxalate stone formation, namely crystal aggregation and crystal adhesion to the renal tubular epithelium of Madin-Darby canine kidney cells. The inhibitory effect of the extracts on stone formation was examined by using a rat model. Sanshishi and Takusha showed a strong inhibitory effect on the calcium oxalate monohydrate crystal aggregation (84.5% and 64.2%, respectively) and on the crystal adhesion to Madin-Darby canine kidney cells (88.2% and 54.6%, respectively). As pretreatment of Madin-Darby canine kidney cells with these two Kampo extracts did not show any inhibitory effect on crystal adhesion, they were considered to mainly affect the crystal surface to block crystal adhesion to Madin-Darby canine kidney cells. Gorin-san, containing both Sanshishi and Takusha, showed significantly stronger inhibitory activities at lower concentrations compared with Chorei-to, which contains Takusha. Finally, Sanshishi showed a prophylactic effect on calcium oxalate crystal deposition in the rat model. These findings suggest that Gorin-san, which contains Sanshishi and Takusha, might be used for the prophylaxis of urolithiasis in humans.


[Contamination of the Czechoslovak section of the Danube by bacteria of the Salmonella group (author's transl)].
120 water samples taken during 1972 and 1973 from 8 profilen of the Danube as well as 15 samples taken from the Morava and the Váh rivers have been examined for salmonella contamination. Salmonellas were present in 60-93.3% of examined water samples taken along the whole Czechoslovak section of the Danube. The results point on the longterm survival of salmonellas and consequently their long-distance contribution by the Danube. We recovered altogether 769 salmonellas belonging to 11 serological groups and to 55 serotypes and lysotypes. The most frequent serotypes were S. enteritidis, typhimurium, agona, derby and panama.


c-Fos degradation by the proteasome. An early, Bcl-2-regulated step in apoptosis.
c-Fos is a transcription factor that promotes cell growth, differentiation, and transformation. We found that c-Fos was degraded when WEHI7.2 mouse lymphoma cells were induced to undergo apoptosis with the calcium ATPase inhibitor, thapsigargin, or the glucocorticoid hormone, dexamethasone. The degradation of c-Fos preceded caspase-3 activation and apoptotic nuclear chromatin condensation and was inhibited by the proteasome inhibitors MG132, N-acetyl-leucyl-leucyl-norleucinal, and lactacystin. Stable transfection of WEHI7.2 cells with a mutant form of c-Fos that was not degraded by the proteasome inhibited apoptosis. Also, overexpression of Bcl-2 in WEHI7.2 cells blocked c-Fos degradation and inhibited apoptosis. The results indicate that proteasome-mediated degradation of c-Fos is an early, Bcl-2-regulated step in apoptosis induction by thapsigargin and dexamethasone. These findings suggest that c-Fos may have a protective action that is eliminated by proteasome-mediated degradation and preserved by Bcl-2.


Asthma and tobacco: double trouble for Wisconsin adolescents.
Environmental tobacco smoke (ETS) exposure has been identified as a cause of asthma and a trigger of asthma attacks in children. We examined the relation of demographic and tobacco-related risk factors to both lifetime asthma diagnosis and the asthma attack rate among Wisconsin adolescents. The impact of asthma on adolescent school absenteeism was also examined. Data used were from the 2004 Wisconsin Youth Tobacco Survey (n=3125), which was administered in a sample of Wisconsin public middle and high schools. Multivariable logistic regression was used to examine risk factors simultaneously. Self-reported lifetime asthma prevalence was 19% among Wisconsin adolescents. Thirty-five percent of adolescents with asthma reported having an asthma attack in the past 12 months. Living with a smoker was a significant predictor of lifetime asthma diagnosis and, among adolescents with asthma, daily ETS exposure was associated with a 2-fold increased risk of having an asthma attack. Being diagnosed with asthma did not deter adolescents from smoking and was a significant predictor of school absenteeism. Asthma is an important health problem for Wisconsin adolescents. Tobacco-related risk factors contribute to the burden of the disease. Interventions to reduce smoking and ETS exposure targeted to adolescents and their guardians are needed. Better asthma control among adolescents could reduce school absenteeism.


Transfer Free Energies and Partitioning of Small Molecules in Collapsed PNIPAM Polymers.
A central quantity in the design of functional hydrogels used as nanocarrier systems, for instance, for drug delivery or adaptive nanocatalysis, is the partition ratio, which quantifies the uptake of a molecular substance by the polymer matrix. By employing all-atom molecular dynamics simulations, we study the solvation and partitioning (with respect to bulk water) of small subnanometer-sized solutes in a dense matrix of collapsed poly( N-isopropylacrylamide) (PNIPAM) polymers above the lower critical solution temperature in aqueous solution. We examine the roles of the solute's polarity and its size on the solubility properties in the thermoresponsive polymer. We show that the transfer free energies of nonpolar solutes from bulk water into the polymer are favorable and scale in a good approximation with the solute's surface area. Even for small solute size variation, partitioning can vary over orders of magnitude. A polar nature of the solute, on the other hand, generally opposes the transfer, at least for alkyl solutes. Finally, we find a strong correlation between the transfer free energies in the gel and the adsorption free energies on a single extended polymer chain, which enables us to relate the partition ratios in the swollen and collapsed state of a PNIPAM gel.


[Conflict of interests and scientific publications].
The potential relationships of interest between authors, reviewers, editors and financial management of the journals can lead to a conflict of interest in their performances. It analyzes the potential conflicts of interest in the papers, with extreme examples, assessing the need for careful statement of the relations, especially economic. Potential conflicts of interest should be transparent and the knowledge and values should be an objective of the magazines. The declaration of relationships should be required in the communication of research, but their existence should not prejudge misconduct.


[Hereditary hemorrhagic telangiectasia associated with von Willebrand's disease; literature review].
A 23-year-old female was admitted to our hospital in July 1987, because of cutaneous macular telangiectasia on her extremities and hypermenorrhea. In 1983, she began to notice small red spots on her palms. During next several years, these telangiectasia increased in number and spread all over her body. In 1986, she had a history of melena and prolonged bleeding after dental extraction. Her lower legs have turned red purple during the gait for a long time. Her older brother and two paternal cousins have experienced frequent epistaxis. The hemostatic laboratory data revealed prolonged IVY bleeding time and APTT, impaired capillary fragility, decreased vWf:Ag and VIII:C levels, depressed Rcof and severe decreased platelet adhesiveness, vWf mobility on two-dimensional crossed immunoelectrophoresis was normal. Platelet aggregation was reduced after addition of ristocetin and collagen. This case was diagnosed Osler-Weber-Rendu disease (Osler disease) associated with von Willebrand's disease (vW disease) type I. Previously, 28 Cases (8 families) with these two disease association have been reported. These disease seems to coexist as an inevitable consequence, because the disorder of vascular endothelial cells where von Willebrand factors are synthesized is a common pathogenetic factor in Osler disease. It is considered that such a case is secondary vW disease. Moreover, previous reports of Osler disease associated with various hemostatic defects are reviewed.


Extended locoregional use of intercostal artery perforator propeller flaps.
Besides conventional flaps, intercostal artery perforator flaps have been reported to cover trunk defects. In this report the use of anterior intercostal artery perforator (AICAP) flap, lateral intercostal artery perforator (LICAP) flap and dorsal intercostal artery perforator (DICAP) flap for thoracic, abdominal, cervical, lumbar and sacral defects with larger dimensions and extended indications beyond the reported literature were reevaluated. Thirty-nine patients underwent surgery between August 2012 and August 2014. The age of the patients ranged between 16 and 79 with a mean of 49 years. The distribution of defects were as follows; 12 thoracic, 8 parascapular, 3 cervical, 8 abdominal, 4 sacral and 4 lumbar. AICAP, LICAP and DICAP flaps were used for reconstruction. Fifty-two ICAP flaps were performed on 39 patients. Flap dimensions ranged between 6 × 9 cm and 14 × 35 cm. Twenty-six patients had single flap coverage and 13 patients had double flap coverage. Forty-six flaps have been transferred as propeller flaps and 6 flaps have been transferred as perforator plus flap. Forty flaps (75%) went through transient venous congestion. In one DICAP flap, 30% of flap was lost. No infection, hematoma or seroma were observed in any patient. Follow-up period ranged between 3 and 32 months with a mean of 9 months. The ICAP flaps provide reliable and versatile options in reconstructive surgery and can be used for challenging defects in trunk.


In Vitro Drug Metabolism Using Liver Microsomes.
Knowledge of the metabolic stability of newly discovered drug candidates eliminated by metabolism is essential for predicting the pharmacokinetic (PK) parameters that underpin dosing and dosage frequency. Further, characterization of the enzyme(s) responsible for metabolism (reaction phenotyping) allows prediction, at least at the qualitative level, of factors (including metabolic drug-drug interactions) likely to alter the clearance of both new chemical entities (NCEs) and established drugs. Microsomes are typically used as the enzyme source for the measurement of metabolic stability and for reaction phenotyping because they express the major drug-metabolizing enzymes cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT), along with others that contribute to drug metabolism. Described in this unit are methods for microsome isolation, as well as for the determination of metabolic stability and metabolite formation (including kinetics). © 2016 by John Wiley & Sons, Inc.


Acremonium sclerotigenum-Acremonium egyptiacum: a multi-resistant fungal pathogen complicating the course of aplastic anaemia.
A patient with aplastic anaemia, successively treated with caspofungin then liposomal amphotericin, developed a disseminated infection due to Acremonium, further confirmed as resistant in vitro to these drugs. Successful treatment was achieved with voriconazole. Multiple antifungal treatments may expose to the risk of breakthrough of multi-resistant pathogens in haematology patients.


Subjective magnitude of auditory impairment. A pilot study.
A study of two samples (one in London, the other in Cairo) of patients who were suffering from an impairment of hearing showed that the subjective magnitude of auditory handicap was significantly correlated to the average hearing level at 2 000 Hz for the two ears. For both samples, the subjective magnitude of the auditory handicap was shown to be a power function of the hearing loss expressed in terms of the sound pressure corresponding to the threshold of hearing. The exponents in the power function applying to the two samples were similar. Age, sex and pain threshold did not influence the estimation of the subjective magnitude of auditory handicap in this study.


PPARγ agonist rosiglitazone alters the temporal and spatial distribution of inflammation during abdominal aortic aneurysm formation.
Research into inflammation during abdominal aortic aneurysm (AAA) formation remains inconclusive. The present study aimed to demonstrate the temporal and spatial distribution of inflammatory cytokines, and to confirm the effect of peroxisome proliferator‑activated receptor γ (PPARγ) on the incidence of AAA formation and the distribution of inflammation in the disease process. Male apolipoprotein E‑/‑ mice were randomly divided into eight groups: Angiotensin II (Ang‑II)‑only 7, 14, 21, 28 and 42 days groups, Ang‑II with rosiglitazone (RGZ) 28 and 42 days groups, and the saline control 42 days group. The early stage was defined as between 7 and 21 days, and the late stage as between 28 and 42 days. Incidences of early rupture and late rupture, aneurysm formation and the maximum diameters of the aorta were recorded. Suprarenal abdominal aortic tissues were collected for histological analysis, and western blotting was performed to reveal the distribution of inflammation. Treatment with Ang‑II caused a significant dilation of the aorta in the late stage; however, this was not observed in the early stage. RGZ reduced the maximum diameters in the late stage. With the pathological process alterations, the inflammatory type shifted. Regarding temporal distribution, the tumor necrosis factor (TNF)‑α expression level was increased over time, and the interleukin (IL)‑10 expression level significantly decreased. When considering the spatial distribution, TNF‑α was expressed dominantly in the aneurysmal body and IL‑10 was dominant in the aneurysmal neck in the late stage. The PPARγ agonist RGZ may reduce the expression of TNF‑α in the late stage and increase the expression level of IL‑10, maintaining the TNF‑α or IL‑10 expression levels at the same levels as in the early stage. Aortic inflammation during AAA formation is dynamic. Protective anti‑inflammatory cytokines are upregulated in the early 'compensatory stage'; however, pro‑inflammatory cytokines are dominant in the late 'decompensatory stage'. PPARγ is likely to continue to upregulate the expression of anti‑inflammatory cytokines, extend the 'compensatory stage', and decelerate the process of AAA development and rupture.


Autonomic dysfunction in ischemic stroke with carotid stenosis.
Impaired autonomic function is common in acute ischemic stroke. Previous limited studies have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the cardiovascular autonomic function. This study sought to investigate cardiovascular autonomic function in patients with ischemic stroke with carotid stenosis. Eighty-five patients with ischemic stroke (58 ones without carotid stenosis and 27 ones with carotid stenosis, average 6 months after stroke onset) and 37 elderly controls were recruited. All performed Ewing's battery autonomic function tests. From Ewing's battery of autonomic function tests, atypical, definite, or severe autonomic dysfunction was identified in 69.0% patients without carotid stenosis and 88.9% with carotid stenosis, with significant difference between the two groups, and the prevalence of autonomic dysfunction in both groups was higher than that in controls (21.6%). Patients with carotid stenosis showed impairment of all parasympathetic tests (all P < 0.05) and one of the sympathetic tests [Mean fall in systolic blood pressure (BP) on standing: P = 0.051], and those without carotid stenosis only showed impairment in two parasympathetic tests (Valsalva ratio: P = 0.014; heart rate response to deep breathing: P < 0.001) in comparison with controls. Patients with carotid stenosis had significantly more impairment than those without carotid stenosis in some autonomic parameters (Valsalva ratio: P < 0.05; mean fall in systolic BP on standing: P < 0.05). Cardiovascular autonomic function is impaired in patients with ischemic stroke, but patients with carotid stenosis show more severely impaired parasympathetic and sympathetic functions.


[Temporal trends of preterm birth and its determinants over a decade].
This study sought to analyze the frequency of preterm births and identify the respective risk factors and their evolution over a decade (2001-2005-2010) in a city in São Paulo state. It is a time-series study using data from the Live Birth Information System. Univariate and multiple logistic regression were used to identify factors associated with preterm births, and linear regression was used to evaluate the time-series tendency of such factors in the period. To avoid underestimation, a correction factor was applied to the preterm frequencies obtained. A discrete increase in preterm birth was observed: 12.5%, 12% and 13.2%. After adjusting for confounding factors, maternal age equal to or higher than 35 years and cesarean sections were associated with higher chances for preterm births and increased over the decade. The number of births in high-risk hospitals and of women with fewer than seven prenatal consultations decreased during the period, while multiple pregnancies remained stable. Compared to vaginal births, cesarean sections doubled the chance of preterm birth. Among the five factors associated with preterm birth, three (cesarean sections, births in high-risk hospitals and fewer than seven prenatal consultations) can be modified by actions taken by health care services.


Integrating ultrasonic tips into the endodontic treatment armamentarium.
The integration of ultrasonic tips in conventional and surgical endodontic treatment can be useful for the clinician. An ultrasonic tip is used in conventional endodontic treatment to remove or bypass a separated instrument or a post within a canal, and can replace a slow-speed handpiece and round bur to detect or provide better access to a canal. In endodontic surgery, the replacement of the slow-speed or miniature handpiece with an ultrasonic tip will allow for better instrument ergonomics and depth of a root-end preparation. When used in conjunction with magnification and illumination, visualization for the clinician is markedly improved. In addition, advancements in polymer science have allowed for the development of plastic ultrasonic tips.


[Ivory Coast uprising and returning Burkinabe immigrants: evaluation of the risk for reemergence of sleeping sickness in Burkina Faso].
Following the sociopolitical unrest that occurred in Ivory Coast in 2002, 360,000 Burkinabe immigrants returned to Burkina Faso that was the epicenter of sleeping sickness last century and is now thought to be free of autochthonous transmission. The purpose of this study was to determine if the massive return of immigrants from human African trypanosomiasis (HAT) endemic areas of Ivory Coast to areas in Burkina Faso where the vector (tsetse fly) is currently present could lead to re-emergence of the disease. Risk areas for re-emergence were identified taking into account the number of returning immigrants, history of the disease, and presence of tsetse flies. Based on these criteria, study was focused on two villages, i.e., Folonzo and Gbalara, located in southern Burkina Faso near the Ivory Coast border. Study in these two villages consisted of characterization of the population (repatriates or not, origin, ...) and medical surveys to assess the presence/absence of the disease. Departure of some returning immigrants from areas including sleeping sickness foci in Ivory Coast (e.g. center west) confirmed the potential risk of re-emergence of the disease. Although no case of sleeping sickness was diagnosed, several serologically positive people were identified and will be followed up. This study failed to demonstrate a clear-cut correlation between massive population movements due to war and reemergence of sleeping sickness. However, this study may have been timed too soon after the return of immigrants to detect reemergence of HAT that could require several years.


Postsynaptic mGluR mediated excitation of neurons in midbrain periaqueductal grey.
Metabotropic glutamate (mGlu) receptors modulate pain from within the midbrain periaqueductal grey (PAG). In the present study, the postsynaptic mGlu receptor mediated effects on rat PAG neurons were examined using whole-cell patch-clamp recordings in brain slices. The selective group I agonist DHPG (10 μM) produced an inward current in all PAG neurons tested which was associated with a near parallel shift in the current-voltage relationship. By contrast, the group II and III mGlu receptor agonists DCG-IV (1 μM) and l-AP4 (3 μM) produced an outward current in only 10-20% of PAG neurons tested. The DHPG induced current was concentration dependent (EC(50) = 1.4 μM), was reduced by the mGlu1 antagonist CPCCOEt (100 μM), and was further reduced by CPCCOEt in combination with the mGlu5 antagonist MPEP (10 μM). The glutamate transport blocker TBOA (30 μM) also produced an inward current, however, this was largely abolished by CNQX (10 μM) plus AP5 (25 μM). Slow EPSCs were evoked following train, but not single shock stimulation, which were enhanced by TBOA (30 μM). The TBOA enhancement of slow EPSCs was abolished by MPEP plus CPCCOEt. These findings indicate that endogenously released glutamate, under conditions in which neurotransmitter spill-over is enhanced, activates group I mGlu receptors to produce excitatory currents within PAG. Thus, postsynaptic group I mGlu receptors have the potential to directly modulate the analgesic, behavioural and autonomic functions of the PAG. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.


Clinical considerations for aesthetic laboratory-fabricated inlay/onlay restorations: a review.
The continued evolution of adhesive technology and materials has increased the application of composite materials for the direct and indirect restoration of posterior dentition. While these innovations cannot address every restorative challenge, such developments do allow clinicians to use conservative preparation designs and varying surface treatments in their efforts to achieve functional and aesthetic results. This discussion details the comprehensive clinical protocol required to use laboratory-fabricated resin systems for inlay/onlay restorations.


The role of hardiness in adjustment to an ostomy.
The purpose of this descriptive study was to explore the effects of the personality characteristic hardiness on adjustment to an ostomy in the elderly ostomy patient. The Health Related Hardiness Scale (HRHS) was used to measure hardiness and the Ostomy Adjustment Scale (OAS) was used to determine adaptation to the ostomy. Results included a modest but significant inverse relationship (-0.3978) (p < 0.05) between the control aspect of hardiness and adjustment to an ostomy. The relationship between hardiness and selected demographic variables was not significant.


Microbiology and prevalence of E2SKAPE-resistant strains in catheter-related bloodstream infections in patients with cancer.
Central venous catheters (CVCs) are essential for treating cancer patients, but infection is a risk associated with their use, particularly by multidrug-resistant (MDR) bacteria. The aim of this study was to describe the microbiology of catheter-related bloodstream infections (CRBSIs) in cancer patients and to compare the prevalence of MDR ESKAPE microorganisms (Enterococcus faecium, Staphylococcus spp, Klebsiella spp, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp) plus Escherichia coli (E2SKAPE). Based on data from 2013 to 2015 from a prospective survey of CRBSIs by the intravenous therapy team, we describe the microbiology and compare the prevalence of MDR E2SKAPE strains between hospitalized patients and outpatients. A total of 469 episodes of CRBSI were diagnosed: 261 (62%) were in women; 87 (18.6%) occurred in hospitalized patients, and 382 (81.4%) in ambulatory patients; 27.5% of patients had a hematologic malignancy and 72.5% a solid tumor. The median time between CVC insertion and CRBSI was 116 days (interquartile range [IQR], 48-207). The most common bacteria isolated were Staphylococcus epidermidis (18.1%), S aureus (10.9%), E coli (7.7%), and Klebsiella spp (8.6%). E2SKAPE accounted for 35.6%. Methicillin-resistant Staphylococcus aureus (MRSA) (odds ratio [OR], 16.4; 95% confidence interval [CI], 1.6-114; P = .01), extended-spectrum beta-lactamase (ESBL) Klebsiella spp (OR, 26; 95% CI, 2-286; P = .007), and ESBL E coli (OR, 26; 95% CI, 2-286; P = .007) were significantly more frequently isolated from hospitalized vs ambulatory patients. MRSA, ESBL E. coli and ESBL Klebsiella spp were significantly more frequently isolated from hospitalized patients with CRBSI.


Cancer incidence of workers in the Finnish pulp and paper industry.
The cancer incidence of 3,545 workers in the Finnish pulp and paper industry was assessed in a retrospective cohort study. The cohort included workers with continuous employment of at least one year between 1 January 1945 and 31 December 1961 and was followed until 31 December 1980. Six subcohorts were formed (sulfite mill, sulfate mill, paper mill, board mill, maintenance department, and power plant). Separate analyses were made for the 2,597 workers hired after 1 January 1945. The smoking habits were surveyed. Among the men, 196 cases of primary cancer were detected versus 203.8 expected [standardized incidence ratio (SIR) 96, 95% confidence interval (95% CI) 82-114], and there were 47 cancer cases among the women versus 57.9 expected (SIR 91, 95% CI 60-108). Lung cancer occurred in 78 men (62.6 expected, SIR 125, 95% CI 98-155), and the excess was the most prominent for the male board mill workers (40 observed, 81.1 expected, SIR 222, 95% CI 158-302), particularly after 20 year's latency (25 observed, 7.8 expected, SIR 323, 95% CI 209-476). Analogous excesses of lung cancer occurred among the men (especially the male board mill workers) who began work after 1 January 1945. The findings were not explained by smoking habits.


Short-term morbidities and neurodevelopmental outcomes in preterm infants exposed to magnesium sulphate treatment.
The aim of the study is to examine whether baseline serum Mg concentration has an impact on short-term and long-term outcomes in preterm infants exposed antenatally to MgSO4. Participants included all infants admitted to the neonatal intensive care unit at <32 weeks of gestational age. Infant serum Mg concentration (iMgC) was examined immediately after birth in those exposed to maternal MgSO4. Data for short-term outcomes were collected from the infants' computerised charts. Neurodevelopmental outcomes at 6-12 months corrected age were assessed using the Griffiths Mental Developmental Scales. Of 197 eligible infants, 145 were exposed to MgSO4. Baseline iMgC was available for 88 infants. Mean iMgC was 3.5 ± 0.88 mg/dL (1.6-5.7 mg/dL). Baseline iMgC was not associated with an increased risk for neither early morbidities nor adverse long-term outcome. However, iMgC above the mean (>3.5 mg/dL) was associated with significantly lower scores on locomotor (P = 0.016) and personal-social (0.041) scales in the first year of life. In a cohort of preterm infants antenatally exposed to MgSO4, elevated baseline iMgC (>3.5 mg/dL) was associated with lower locomotor scores. Further research is needed in order to study the relationship between supra-physiologic iMgC and its effect on the developing brain.


Bottleneck limitations for microRNA-based therapeutics from bench to the bedside.
MicroRNAs are endogenous non-coding small RNAs that repress expression of a broad array of target genes. Research into the role and underlying molecular events of microRNAs in disease processes and the potential of microRNAs as drug targets has expanded rapidly. Significant advances have been made in identifying the associations of microRNAs with cancers, viral infections, immune diseases, cardiovascular diseases, wound healing, biological development and other areas of medicine. However, because of intense competition and financial risks, there is a series of stringent criteria and conditions that must be met before microRNA-based therapeutics could be pursued as new drug candidates. In this review, we specifically emphasized the obstacles for bench-based microRNA to the bedside, including common barriers in basic research, application limitations while moving to the clinic at the aspects of vector delivery, off-target effects, toxicity mediation, immunological activation and dosage determination, which should be overcome before microRNA-based therapeutics take their place in the clinic.


Nanoparticle approaches to combating drug resistance.
Multidrug resistance (MDR) among cancer cells is a serious impediment to the success of conventional chemotherapy. The emergence of nanomedicine demonstrates great promise in overcoming MDR through multiple mechanisms. Nanoparticles have been shown to overcome the MDR at the tissue level through increased intratumoral accumulation resulting from enhanced permeation and retention, neovascular cell targeting, and externally triggered local drug release. Nanoparticles have also demonstrated the ability to overcome the MDR at the cellular/subcellular level by enhancing intracellular drug accumulation, improving drug-target accessibility, or even interfering with existing MDR mechanisms.


Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. First communication: plasma concentration, distribution, metabolism and excretion of the new monoclonal antibody, regavirumab after intravenous administration in rats and rabbits.
TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was investigated in rats and rabbits. Plasma concentrations of radioactivity were shown to increase dose-dependently after 2, 10 or 50 mg/kg of 125I-labeled TI-23 was administered intravenously to rats. Their elimination of half-lives from plasma were 11-13 days. The radioactivity in plasma corresponded with the idiotype activity (antigenicity against idiotype antibody) of the monoclonal antibody. No significant difference was detected in plasma concentration and half-lives between male and female rats. Quantitative and qualitative distribution studies demonstrated that high radioactivity was distributed predominantly to the blood and blood-rich organs. The idiotype activity which remained in those tissues was attributable to the blood in the tissues. The radioactivity was mainly excreted in the urine as free iodine, and about 40% of the dose remained in the body. After the rabbits received 2 mg/kg of 125I-TI-23, the initial radioactivity in plasma was higher than in rats, and a larger distribution volume and shorter elimination half-lives of radioactivity in plasma were observed.


Real-time shimming to compensate for respiration-induced B0 fluctuations.
In MRI of human brain, the respiratory cycle can induce B0-field fluctuations through motion of the chest and fluctuations in local oxygen concentration. The associated NMR frequency changes can affect the MRI data in various ways and lead to temporal signal fluctuations, and image artifacts such as ghosting and blurring. Since the size of the effect scales with magnetic field strength, artifacts become particularly problematic at fields above 3.0T. Furthermore, the spatial dependence of the B0-field fluctuations complicates their correction. In this work, a new method is presented that allows compensation of field fluctuations by modulating the B0 shims in real time. In this method, a reference scan is acquired to measure the spatial distribution of the B0 effect related to chest motion. During the actual scan, this information is then used, together with chest motion data, to apply compensating B0 shims in real time. The method can be combined with any type of scan without modifications to the pulse sequence. Real-time B0 shimming is demonstrated to substantially improve the phase stability of EPI data and the image quality of multishot gradient-echo (GRE) MRI at 7T.


Failure to detect human papillomavirus in focal cortical dysplasia type IIb.
Recent studies have reported evidence of human papillomavirus 16 (HPV-16) in a very high proportion of pathological specimens of focal cortical dysplasia type IIb, but not in control specimens, motivating the proposal that viral infection during fetal development may play a causal role in the pathogenesis of focal cortical dysplasias. However, the significance of the association between HPV infection and focal cortical dysplasia type IIb, and its reproducibility across surgical centers, remain unclear. Here we sought evidence for HPV-16 in an independent cohort of surgical specimens. We identified 14 specimens of focal cortical dysplasia type IIb from a single surgical center between 1995 and 2013. Multiple methods were used to establish presence or absence of HPV, including DNA polymerase chain reaction, conventional in situ hybridization, chromogenic in situ hybridization, and immunohistochemistry for p16. We found no conclusive evidence of HPV in any of the specimens. All but 1 of the cases were negative by >1 method. These results raise questions about the prevalence of HPV infection in focal cortical dysplasias and about its potential importance as a causative agent.


Pharmacologic treatment of desmoid tumors in familial adenomatous polyposis: results of an in vitro study.
Desmoid tumors (DTs), the result of an abnormal proliferation of connective tissue, occur frequently in familial adenomatous polyposis. Treatment of DT is difficult because of the high rate of recurrence after operation. Recently, antiestrogens and nonsteroidal antiinflammatory drugs have been used with good results as inhibitors of DT cell proliferation. In this report we performed in vitro studies on cultured desmoid cells and skin fibroblasts of four patients who underwent surgical resection of DT and normal skin biopsy. We evaluated the expression of estrogen receptors and the mitogenic effect of 17 beta-estradiol and sulindac, a nonsteroidal antiinflammatory compound, on cell proliferation and collagen synthesis of desmoid cells. Proliferation and collagen synthesis of desmoid cells were stimulated by 17 beta-estradiol, and tamoxifen, an antiestrogenic compound, inhibited this effect. Desmoid cells also expressed estrogen receptors. Moreover, growth of desmoid cells from one of the patients was inhibited by sulindac. The in vitro evaluation of drug responsiveness in patients operated on for DT could be used as both a prognostic tool in the natural history of DT and in addressing pharmacologic therapy in this disorder.


Scalp distribution of early (0 to 10 msec) auditory evoked responses.
Auditory nerve and brain stem evoked responses were summated from multiple scalp and earlobe electrodes from five subjects with normal hearing to determine the spatial voltage relationships along the coronal and/or sagital planes that make up the electrode array. All recordings maintained their positive polarity, and polarity inversions were not observed at any cephalic sites; thus, a null potential line was not identified for these short-latency potentials at the scalp. Less distinct potentials were derived from the earlobes when referenced to the chin. Linked earlobes generated some potentials of negative polarity. These observations lend additional support to the concept that early auditory scalp potentials are most likely generated from far field neural aggregates located caudally to the auditory cortex.


Comparative effects of Rauwolfia vomitoria and chlorpromazine on locomotor behaviour and anxiety in mice.
Since remedies for mental disorders have been sought through both orthodox and traditional medicine this study compared the effects of the antipsychotic, chlorpromazine (Cpz), the herb Rauwolfia vomitoria (RV) and its alkaloid reserpine (Res) in mice. Ninety male CD-1 strain of mice (75-80 days old; 30-34 g body weight) were divided into 3 major groups and each consisting 5 subgroups (n=6). Cpz (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.), was administered 30 min before testing. RV (0.0, 0.25, 1.0, 2.0 and 4.0 mg/kg, i.p.) and Res (0.0, 0.1, 0.4, 0.8, 1.6 mg/kg, i.p.) were administered 24 h before testing. The open field test was used to assess locomotor and exploratory behaviour, acceleratory rotarod for motor coordination, light/dark box for anxiety. CPZ dose-dependently decreased locomotor and exploration behaviour and impaired motor coordination (p<0.01). RV also decreased locomotor behaviour at 4.0 mg/kg (p<0.5) but did not alter exploration and motor coordination. Res however, decreased locomotion and exploration and impaired motor coordination 0.8 and 1.6 mg/kg (p<0.05). In the light/dark box, CPZ increased anxiety related behaviour at 1.0, 2.0 mg/kg (p<0.05) whereas RV dose-dependently decreased anxiety from 1.0 to 4.0 mg/kg (p<0.01). Res, unlike RV, dose-dependently increased anxiety related behaviour from 0.4 to 1.6 mg/kg. Root bark extract from Rauwolfia vomitoria produced better behavioural effects with less distortion in motor coordination when compared to chlorpromazine and so has a great potential as an alternative antipsychotic agent compared to chlorpromazine. Since Res did not produce same effects as RV, the effect of RV may not be due solely to Res as claimed.


Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the human fetal and adult male reproductive tracts.
The first rate-limiting step in the conversion of arachidonic acid to PGs is catalyzed by cyclooxygenase (Cox). Two isoforms of Cox have been identified, Cox-1 (constitutively expressed) and Cox-2 (inducible form), which are the products of two different genes. In this study we describe the immunohistochemical localization of Cox-1 and -2 in the human male fetal and adult reproductive tracts. There was no Cox-1 expression in fetal samples (prostate, seminal vesicles, or ejaculatory ducts), and only minimal expression in adult tissues. There was no expression of Cox-2 in the fetal prostate. In a prepubertal prostate there was some Cox-2 expression that localized exclusively to the smooth muscle cells of the transition zone. In adult hyperplastic prostates, Cox-2 was strongly expressed in smooth muscle cells, with no expression in the luminal epithelial cells. Cox-2 was strongly expressed in epithelial cells of both fetal and adult seminal vesicles and ejaculatory ducts. The Cox-2 staining intensity in the fetal ejaculatory ducts during various times of gestation correlated with previously reported testosterone production rates by the fetal testis. These data indicate that Cox-2 is the predominant isoform expressed in the fetal male reproductive tract, and its expression may be regulated by androgens. The distinct cell type-specific expression patterns of Cox-2 in the prostate (smooth muscle) vs. the seminal vesicles and ejaculatory ducts (epithelium) may reflect the different roles of PGs in these tissues.


Disordered nuclear pasta, magnetic field decay, and crust cooling in neutron stars.
Nuclear pasta, with nonspherical shapes, is expected near the base of the crust in neutron stars. Large-scale molecular dynamics simulations of pasta show long lived topological defects that could increase electron scattering and reduce both the thermal and electrical conductivities. We model a possible low-conductivity pasta layer by increasing an impurity parameter Q_{imp}. Predictions of light curves for the low-mass x-ray binary MXB 1659-29, assuming a large Q_{imp}, find continued late time cooling that is consistent with Chandra observations. The electrical and thermal conductivities are likely related. Therefore, observations of late time crust cooling can provide insight on the electrical conductivity and the possible decay of neutron star magnetic fields (assuming these are supported by currents in the crust).


One program's experience of OSCE vs. written board certification results: a pilot study.
The objective structured clinical examination (OSCE) has been the focus of a lot debate with respect to reliability and validity. Much of the controversy surrounding these components lies in a lack of comparison with a "gold standard." Further work is needed to improve the evaluation of clinical skills to the point that a gold standard can truly be said to exist.


Molecular Characterization of a Rare Dedifferentiated Liposarcoma With Rhabdomyosarcomatous Differentiation in a 24 Year Old.
Aims. The aim of this study was to identify potential driver genetic alterations in a dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. Methods and Results. A 24-year-old female underwent resection of an abdominal mass, which on a previous biopsy demonstrated rhabdomyosarcomatous differentiation concerning for embryonal rhabdomyosarcoma. Histologically the resected tumor displayed a high-grade sarcoma with rhabdomyosarcomatous differentiation in the background of well-differentiated liposarcoma consistent with DDLPS. Fluorescence in situ hybridization confirmed MDM2 amplification, as did array-based copy number profiling. Whole-exome sequencing revealed a somatic FGFR1 hotspot mutation and RNA sequencing an LMNB2-MAP2K6 fusion only within the dedifferentiated component. Conclusions. This study represents an in-depth examination of a rare DDLPS with rhabdomyosarcomatous differentiation in a young individual. Additionally, it is also instructive of a potential pitfall when assessing for MDM2 amplification in small biopsies. Despite exhaustive analysis, mutation and gene copy number analysis did not identify any molecular events that would underlie the rhabdomyoblastic differentiation. Our understanding of what causes some tumors to dedifferentiate as well as undergo divergent differentiation is limited, and larger studies are needed.


Bacillus cereus biofilm formation on central venous catheters of hospitalised cardiac patients.
Formation of bacterial biofilms is a risk with many in situ medical devices. Biofilm-forming Bacillus species are associated with potentially life-threatening catheter-related blood stream infections in immunocompromised patients. Here, bacteria were isolated from biofilm-like structures within the lumen of central venous catheters (CVCs) from two patients admitted to cardiac hospital wards. Isolates belonged to the Bacillus cereus group, exhibited strong biofilm formation propensity, and mapped phylogenetically close to the B. cereus emetic cluster. Together, whole genome sequencing and quantitative PCR confirmed that the isolates constituted the same strain and possessed a range of genes important for and up-regulated during biofilm formation. Antimicrobial susceptibility testing demonstrated resistance to trimethoprim-sulphamethoxazole, clindamycin, penicillin and ampicillin. Inspection of the genome revealed several chromosomal β-lactamase genes and a sulphonamide resistant variant of folP. This study clearly shows that B. cereus persisting in hospital ward environments may constitute a risk factor from repeated contamination of CVCs.


Cis-regulated alternative splicing divergence and its potential contribution to environmental responses in Arabidopsis.
Alternative splicing (AS) plays key roles in plant development and the responses of plants to environmental changes. However, the mechanisms underlying AS divergence (differential expression of transcript isoforms resulting from AS) in plant accessions and its contribution to responses to environmental stimuli remain unclear. In this study, we investigated genome-wide variation of AS in Arabidopsis thaliana accessions Col-0, Bur-0, C24, Kro-0 and Ler-1, as well as their F1 hybrids, and characterized the regulatory mechanisms for AS divergence by RNA sequencing. We found that most of the divergent AS events in Arabidopsis accessions were cis-regulated by sequence variation, including those in core splice site and splicing motifs. Many genes that differed in AS between Col-0 and Bur-0 were involved in stimulus responses. Further genome-wide association analyses of 22 environmental variables showed that single nucleotide polymorphisms influencing known splice site strength were also associated with environmental stress responses. These results demonstrate that cis-variation in genomic sequences among Arabidopsis accessions was the dominant contributor to AS divergence, and it may contribute to differences in environmental responses among Arabidopsis accessions.


Functionalization of medical cotton by direct incorporation of silver nanoparticles.
Medical cotton is usually used to clean skin, pack wounds and in other surgical tasks. Such important usages make imparting the antibacterial property to medical cotton is so essential research. The current research focuses on functionalization of medical cotton by direct incorporation of silver nanoparticles (AgNPs) in two-step process namely, pre-alkalization followed by sorption. Decorative color and antibacterial action were accomplished for medical cotton after in situ incorporation of AgNPs without using any other external reducing agent. AgNPs were produced due to the reduction action of alcoholic and aldehydic groups of cotton's skeletal blocks. Cotton fibers were acquired a decorative color attributed to surface plasmon resonance of AgNPs. The treated cotton was characterized by using electron microscope. Results showed that Ag(0) with size distribution of 0-160 nm was formed in the cotton fibers and their size majority (70%) was less than 80 nm. The reduction of Ag(+) to Ag(0) was confirmed by measuring the carboxylic and aldehydic contents. The treated cotton exhibited excellent antibacterial action at low silver contents. The absorbency of cotton was not affected by treatment. The produced medical cotton could be used to safe cleaning of wounds without getting any microbial infections.