Exercise, Skeletal Muscle and Circulating microRNAs.
Regular exercise stimulates numerous structural, metabolic, and morphological adaptations in skeletal muscle. These adaptations are vital to maintain human health over the life span. Exercise is therefore seen as a primary intervention to reduce the risk of chronic disease. Advances in molecular biology, biochemistry, and bioinformatics, combined with exercise physiology, have identified many key signaling pathways as well as transcriptional and translational processes responsible for exercise-induced adaptations. Noncoding RNAs, and specifically microRNAs (miRNAs), constitute a new regulatory component that may play a role in these adaptations. The short single-stranded miRNA sequences bind to the 3' untranslated region of specific messenger RNAs (mRNAs) on the basis of sequence homology. This results in the degradation of the target mRNA or the inhibition of protein translation causing repression of the corresponding protein. While tissue specificity or enrichment of certain miRNAs makes them ideal targets to manipulate and understand tissue development, function, health, and disease, other miRNAs are ubiquitously expressed; however, it is uncertain whether their mRNA/protein targets are conserved across different tissues. miRNAs are stable in plasma and serum and their altered circulating expression levels in disease conditions may provide important biomarker information. The emerging research into the role that miRNAs play in exercise-induced adaptations has predominantly focused on the miRNA species that are regulated in skeletal muscle or in circulation. This chapter provides an overview of these current research findings, highlights the strengths and weaknesses identified to date, and suggests where the exercise-miRNA field may move into the future.


New directions in pharmacological treatment of acromegaly.
The aim of treatment for acromegaly is to control tumour growth, relieve symptoms and ensure biochemical cure. With specific, well-tolerated medication, long-time primary or preoperative treatment should be discussed. A PubMed search for literature ('somatostatin' and 'pituitary') was performed to explore different medical treatment options in today's clinics, which often use a combination of modalities. Clinical trial databases (ClinicalTrials.gov) were also searched for current clinical studies on acromegaly in order to reassess new directions in medical treatment. The cornerstone for medical treatment is somatostatin analogues (SAs). SAs control tumour growth and hormone hypersecretion in most patients. There seems, however, to be dissociation between the antisecretory and antiproliferative effects. New analogues with high affinity for other somatostatin receptor (SSTR) subtypes are being investigated. Chimeric compounds, which bind the SSTR as well as the dopamine receptor, are new potential alternatives. Patients not controlled on SAs (or dopamine agonists, or a combination) will be evaluated for treatment with the highly effective growth hormone receptor antagonist, as monotherapy or in combination with SAs. With the variety of medications we have today and those expected to come into clinical use in coming years, acromegaly can be controlled in almost all patients. There has already been a drift towards medical treatment also as a primary option, and it is to be expected that this will continue. Treatment should be tailored for the individual case, also taking into account long-term effects, convenience for the patient and costs for society.


Insulin resistance in PCOS.
Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy affecting women of reproductive age, manifested with a variety of clinical signs, none of which is pathognomonic. The association of insulin resistance and reproductive abnormalities with clinical hyperandrogenism in a woman was first demonstrated by Achard and Thiers in the "diabetes of bearded woman." The link of PCOS with insulin resistance was subsequently established by clinical studies characterizing the profound insulin resistance in obese and lean PCOS patients. Insulin resistance, hyperinsulinemia, and beta-cell dysfunction are very common in PCOS, but are not required for the diagnosis. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS found a broad clinical application in the management of the syndrome, where the regulation of cycle abnormalities and the facilitation of pregnancy in obese PCOS patients was assisted by co-administration of agents such as the well-known insulin sensitizers. The documentation of the presence of insulin resistance contributed substantially to unravel several metabolic components present in the syndrome. Today our knowledge about PCOS appears to have broader health implications and to have profoundly altered our view of the gravity of this condition.


Effects of adalimumab treatment on endothelial cell activation markers in the skeletal muscle of patients with rheumatoid arthritis.
Patients with rheumatoid arthritis (RA), particularly those with severe disease, have increased risk of cardiovascular disease (CVD). Previous studies suggest that endothelial cell activation may contribute to this co-morbidity, and that treatment with tumour necrosis factor (TNF) inhibitors could reduce the risk of CVD in these patients. The aim of this study was to investigate endothelial cell activation markers in muscle tissue of patients after adalimumab treatment. Patients with active RA who started treatment with adalimumab 40 mg every two weeks were included. Muscle biopsies taken before and 3 months after start of treatment were available from 11 patients (9 females, mean age 54.2 years, median disease duration 6.5 years, 91% anti-CCP positive, 7 on methotrexate [median dose 20 mg/week]). None of the patients had clinical signs of myopathy. IL-1α and HLA-DQ were investigated by immunohistochemistry. Quantification was performed by computer assisted image analysis. Disease activity, measured by DAS28 decreased (mean 5.5 vs. 4.1; p=0018). A good or moderate EULAR response was seen in 6/11 patients. HLA-DQ was mainly expressed in endothelial cells in capillaries, whereas IL-1α was mainly seen in larger vessels. HLA-DQ expression decreased significantly after treatment (p=0.041). There was a similar trend for IL-1α, in particlar in EULAR good/moderate responders. Adalimumab treatment was associated with decreased expression of endothelial markers previously associated with severe systemic inflammation in RA. Our findings indicate a reduced endothelial activation in patients treated with anti-TNF drugs, which might contribute to a lower risk of cardiovascular co-morbidity.


Analysis of electroretinogram during systemic hypercapnia with intraretinal K(+)-microelectrodes in cats.
Systemic hypercapnia alters the intraretinal pH and metabolism and profoundly affects the vitreal electroretinogram (ERG). Using intraretinal K(+)-selective microelectrodes (ISMs), the authors examined the effects of systemic hypercapnia on ERG in the intact cat eye in vivo. Double-barreled K(+)-ISMs were used to record intraretinal, light-evoked [K+]o decrease, intraretinal ERG, vitreal ERG, and standing potential (SP) in the dark-adapted retina. Hypercapnia was induced by adding CO2 to the inhaled mixture of gas (without significant hypoxia). The standing potential was elevated, and the vitreal ERG c-wave increased in amplitude whereas the b-wave decreased during hypercapnia. Intraretinal recordings showed that the amplitudes of slow PIII and the transepithelial (TEP) c-wave decreased. The slow PIII decreased more than the TEP c-wave. The light-evoked [K+]o decrease also was reduced, but no change was noted in the subretinal [K+]o. The neural retina was more sensitive than the retinal pigment epithelium to the intraretinal acidification caused by systemic hypercapnia. However, the change in the SP and b-wave suggested complicated effects other than acidosis.


Structure and functional properties of Capto™ Core 700 core-shell particles.
Capto™ Core 700 is a core-shell chromatographic support with an adsorbing core contained within an inert shell layer designed to purify larger biomolecules and bioparticles in a flow-through mode. The present study aims to characterize the structure and functional properties of this resin using bovine serum albumin (BSA, Mr~65 kDa) and thyroglobulin (Tg, Mr~660 kDa) as model impurity proteins. The functionalized adsorbing core and the inert shell have the same fibrous structure typical of agarose-based beads. The resin average bead size is 90.7 μm with a range of 50-130 μm, the shell thickness is 4.18 µm with a range of 3-6 µm and a standard deviation of 0.55 µm, and the pore radius, obtained by inverse size exclusion chromatography, is 50.4 ± 1.3 nm. Both proteins present highly favorable binding isotherms with maximum binding capacities of 55 and 105 mg/mL of total bead volume for BSA and Tg, respectively. The addition of 500 mM NaCl reduces the binding capacity by less than 50%, showing the ability of the resin to operate at high salt conditions. For both proteins, the effective pore diffusivity in the core is smaller than in the shell due to additional hindrance by bound protein in the core area. Effective pore diffusivities values in the core are 1.6 × 10-7 and 0.16 × 10-7 cm2/s for BSA and Tg, respectively. The DBC10% at 2 min residence time are 24 and 2 mg/mL for BSA and Tg, respectively. This study provides qualitative and quantitative information about Capto™ Core 700 resin. This information could be used to predict and optimize the purification of large biomolecules and bioparticle in route to the establishment of more effective downstream processes.


Provider and Nonprovider Sources of Mental Health Help in the Military and the Effects of Stigma, Negative Attitudes, and Organizational Barriers to Care.
This study examined sources of help (providers or nonproviders) used by soldiers for mental health problems. Differences in perceived barriers to care by type of help used were also assessed. Active-duty soldiers from four brigade combat teams (N=3,380) were surveyed in 2008-2009. Items assessed posttraumatic stress disorder; depression; anxiety; help needed because of a stress, emotional, alcohol, or family problem; stigma; negative attitudes toward care; and organizational barriers. Participants reported receipt of help in the past three months from providers (mental health or medical professionals or an Army resource hotline) or nonproviders (fellow soldier, medic, chaplain, or chain of command). Nearly a third (31%) were identified as being in need of mental health care. Of those, 5% reported using nonprovider help exclusively, 14% used provider help exclusively, and 7% used both types. Stigma was rated significantly lower as a barrier among those who used help exclusively from providers than among those who did not use help from any source; however, no significant differences in stigma scores were found between those who used help from nonproviders and those who did not use help from any source. Soldiers who used help from nonproviders were more likely than those who used help from providers to perceive organizational barriers. Results show that soldiers may view nonproviders as alternative sources of mental health help, suggesting that the Army should ensure that such resources are adequately trained and integrated into the mental health community so that soldiers can receive the help they need.


Sequential transfection of RUNX2/SP7 and ATF4 coated onto dexamethasone-loaded nanospheresenhances osteogenesis.
The timing of gene transfection greatly influences stem cell differentiation. Sequential transfection is crucial for regulation of cell behavior. When transfected several days after differentiation initiation, genes expressed at the late stage of differentiation can regulate cell behaviors and functions. To determine the optimal timing of key gene delivery, we sequentially transfected human mesenchymal stem cells (hMSCs). This method can easily control osteogenesis of stem cells. hMSCs were first transfected with RUNX2 and SP7 using poly(lactic-co-glycolic acid) nanoparticles to induce osteogenesis, and then with ATF4 after 5, 7, and 14 days. Prior to transfecting hMSCs with all three genes, each gene was individually transfected and its expression was monitored. Transfection of these genes was confirmed by RT-PCR, Western blotting, and confocal microscopy. The pDNAs entered the nuclei of hMSCs, and RUNX2 and SP7 proteins were translated and triggered osteogenesis. Second, the ATF4 gene was delivered when cells were at the pre-osteoblasts stage. To induce the osteogenesis of hMSCs, the optimal timing of ATF4 gene delivery was 14 days after RUNX2/SP7 transfection. Experiments in 2- and 3-dimensional culture systems confirmed that transfection of ATF4 at 14 days after RUNX2/SP7 promoted osteogenic differentiation of hMSCs.


The Year in Cardiology 2013: arrhythmias.
The Year in Cardiology 'arrhythmias' presents an update on the latest studies and innovations published in the field within the last 12 months. Recent advances in the management of atrial fibrillation and novel treatment strategies and technologies are presented. New consensus documents to improve the diagnosis and treatment of patients with inherited cardiac arrhythmias and for paediatric patients with cardiac arrhythmias are summarized. Great progress has also been made in the field of cardiac implantable electronic devices: improvements in implantation techniques and novel technologies have been introduced and successfully applied. In addition, novel data on prevention of implantable cardioverter defibrillator-shocks and cardiac resynchronization therapy will certainly help to improve the quality of care for patients with cardiac arrhythmias and heart failure.


[Computerized tomography in the evaluation of the state of the retroperitoneal lymph nodes].
The authors consider the potentialities of computerized tomography (CT) in the diagnosis of lesions of the retroperitoneal lymph nodes in their metastatic involvement and hemoblastoses. CT data on 142 patients with hemoblastoses and tumors of different sites are discussed. This type of examination made it possible to reveal the involvement of the retroperitoneal lymph nodes in 59 patients resulting in the diagnosis of the generalization of the underlying disease in 41.5% of the cases. CT makes it possible to correctly interpret the state of practically all groups of the retroperitoneal lymph nodes. Besides, CT gives an opportunity to detect lymph node enlargement in the negative results of lymphography or to reveal lesions of some groups of the lymph nodes which are inaccessible to contrast examination, all of these being of great importance for the planning of radiation or surgical treatment. CT provides an opportunity for a dynamic control over therapeutic results both in hospitals and in polyclinics. The results of the examination were of importance in each case for the choice of the tactics and method of specific therapy as well as for prognosis of a subsequent source of the underlying disease.


Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis.
Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively evaluated. The authors conducted a nested case-control study to assess the association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors, and hospitalization for acute renal failure. They identified 121,722 new NSAID users older than age 65 years from the administrative health care databases of Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on age and follow-up time were analyzed by using conditional logistic regression, adjusted for sex, age, health status, health care utilization measures, exposure to contrast agents, and nephrotoxic medications. The risk of acute renal failure for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and receded thereafter. The association with acute renal failure within 30 days of therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08), naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54, 95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p = 0.057). There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.


Failure of Helicobacter pylori eradication: is poor compliance the main cause?
The aim of the study was to evaluate whether poor compliance can be considered as the main cause of the low Helicobacter pylori (H. pylori) eradication rate observed in an ambulatory population. Seventy-eight patients with non-ulcer dyspepsia or gastroduodenal ulcer in whom H. pylori infection was confirmed by urease Clo-test and histology or bacterial culture, received a 1-week triple therapy comprising lansoprazole 30 mg b.d., amoxicillin 1000 mg b.d. and clarithromycin 500 mg b.d. Compliance was assessed using MEMS(R) containers (Medication Event Monitoring System) which recorded time of medicines consumption. The overall H. pylori eradication rate was 65.4% (95% CI: 54.8-76.0%) (intention to treat). Sixty-nine subjects (88.5%) consumed greater than 85% of doses and were considered as "good compliers". The major reason listed by the nine remaining patients for stopping treatment prematurely was side effects. In the population categorised as "good compliers", H. pylori eradication rate was 69.6% (95% CI: 58.7-80.5%) (per protocol) indicating that compliance could not be considered as the sole reason for treatment failure. Bacterial culture in a subset of 30 patients further showed a H. pylori eradication rate of 73.9% (95% CI: 55.7-92.1%) in "good compliers" with a clarithromycin-sensitive H. pylori strain. On multivariate analysis, H. pylori eradication was inversely associated with poor compliance (P=0.029). Presence of a gastroduodenal ulcer, age, gender and smoking habit did not differ significantly between the eradicated and noneradicated groups. Although poor compliance and bacterial resistance were important factors in determining treatment success in our population, they could only explain 40% of failures suggesting that other factors must be involved.


Graphene-Based Analog of Single-Slit Electron Diffraction.
This work reports the experimental demonstration of single-slit diffraction exhibited by electrons propagating in encapsulated graphene with an effective de Broglie wavelength corresponding to their attributes as massless Dirac fermions. Nanometer-scale device designs were implemented to fabricate a single-slit followed by five detector paths. Predictive calculations were also utilized to readily understand the observations reported. These calculations required the modeling of wave propagation in ideal case scenarios of the reported device designs to more accurately describe the observed single-slit phenomenon. This experiment was performed at room temperature and 190 K, where data from the latter highlighted the exaggerated asymmetry between electrons and holes, recently ascribed to slightly different Fermi velocities near the K point. This observation and device concept may be used for building diffraction switches with versatile applicability.


A uremic solute, P-cresol, inhibits the proliferation of endothelial progenitor cells via the p38 pathway.
Endothelial dysfunction is a consistent finding in uremic patients. Whether the uremic solutes, p-cresol and indoxyl sulfate, affect the cellular function of endothelial progenitor cells (EPCs) was tested. EPCs were isolated from healthy adults and treated with p-cresol (10-80 μg/ml) or indoxyl sulfate (25-200 μg/ml) with ranges of concentration similar to those found in uremic patients. The effect of p-cresol or indoxyl sulfate on the viability of EPCs was examined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro angiogenesis of EPCs was tested by a matrigel assay. Signal pathways activated by these solutes were also studied. The viability of EPCs was dose- and time- dependently inhibited by p-cresol and indoxyl sulfate, respectively (both P < 0.05). The angiogenesis capacity of EPCs was suppressed significantly by p-cresol but not by indoxyl sulfate. Phosphorylated p38 and Erk1/2 was increased by p-cresol, while P38 inhibitor SB203580 reversed the effect of p-cresol in the MTT assay. Notably, a dose of 80 μg/ml p-cresol decreased the Notch1 intracellular domain level in EPCs. This study has demonstrated that p-cresol inhibits proliferation of EPCs via activation of p38 MAPK pathways. P-cresol also attenuates angiogenesis function of EPCs and interferes with the Notch1 path-way.


Actinobacillus actinomycetemcomitans prosthetic valve endocarditis.
Actinobacillus actinomycetemcomitans, a fastidious gram-negative bacillus, has been reported as the cause of prosthetic valve endocarditis in 11 patients. Two additional patients are reported and the literature is reviewed. All cases occurred greater than 1 year after implantation of the prosthesis. Six of the 13 patients had had recent dental work or had poor dentition. Three patients had received endocarditis prophylaxis. Ten of 13 were cured with antibiotics alone. Only one patient suffered from congestive heart failure, and only one had documented evidence of major systemic emboli during antimicrobial therapy. Valve replacement was necessary in only two during antimicrobial therapy. A actinomycetemcomitans should be considered as a possible etiologic agent in late prosthetic valve endocarditis, particularly when blood cultures are initially negative. A regimen of a beta-lactam antibiotic in combination with an aminoglycoside is recommended for 4-6 weeks. The excellent in vitro activity of the third-generation cephalosporins and rifampin promise new therapeutic options.


Flunarizine suppresses endothelial Angiopoietin-2 in a calcium - dependent fashion in sepsis.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection leading to systemic inflammation and endothelial barrier breakdown. The vascular-destabilizing factor Angiopoietin-2 (Angpt-2) has been implicated in these processes in humans. Here we screened in an unbiased approach FDA-approved compounds with respect to Angpt-2 suppression in endothelial cells (ECs) in vitro. We identified Flunarizine - a well-known anti-migraine calcium channel (CC) blocker - being able to diminish intracellular Angpt-2 protein in a time- and dose-dependent fashion thereby indirectly reducing the released protein. Moreover, Flunarizine protected ECs from TNFα-induced increase in Angpt-2 transcription and vascular barrier breakdown. Mechanistically, we could exclude canonical Tie2 signalling being responsible but found that three structurally distinct T-type - but not L-type - CC blockers can suppress Angpt-2. Most importantly, experimental increase in intracellular calcium abolished Flunarizine's effect. Flunarizine was also able to block the injurious increase of Angpt-2 in murine endotoxemia in vivo. This resulted in reduced pulmonary adhesion molecule expression (intercellular adhesion molecule-1) and tissue infiltration of inflammatory cells (Gr-1). Our finding could have therapeutic implications as side effects of Flunarizine are low and specific sepsis therapeutics that target the dysregulated host response are highly desirable.


Turn-on, fluorescent nuclear stains with live cell compatibility.
DNA-binding, green and yellow fluorescent probes with excellent brightness and high on/off ratios are reported. The probes are membrane permeable, live-cell compatible, and optimally matched to 405 nm and 514 nm laser lines, making them attractive alternatives to UV-excited and blue emissive Hoechst 33342 and DAPI nuclear stains. Their electronic structure was investigated by optical spectroscopy supported by TD-DFT calculations. DNA binding is accompanied by 27- to 75-fold emission enhancements, and linear dichroism demonstrates that one dye is a groove binder while the other intercalates into DNA.


The significance of high-density lipoproteins (HDL) in the clearance of intravenously administered bacterial lipopolysaccharides (LPS) in mice.
The direct immunofluorescence technique was used to study the presence of high-density lipoproteins (HDL) in the liver, spleen and kidney of mice before and after intravenous administration of purified lipopolysaccharides (LPS) from Escherichia coli O 75, Salmonella abortus equi and Salmonella minnesota R 595, as well as free lipid A. Untreated mice had small granules of HDL in the hepatocellular cytoplasm, which appeared more pronounced after oral administration of fat. After intravenous administration of LPS, hepatocellular HDL decreased continuously and was no longer visible 1 hour after injection of LPS or lipid A. Five to ten minutes after administration, smooth-form LPS were located in sinusoidal cells, and rough form LPS and lipid A were found in both parenchymal and nonparenchymal liver cells. All toxins were demonstrated in both cell populations 1-4 hours after injection. The spleen was free of HDL, while there was a strong uptake of LPS into the cells of the reticulo-endothelial system. The kidney of experimental mice had small HDL granules in the epithelial cells of the proximal tubules, with a tendency to move to the lumen 1 hour after LPS injection, while there was a transient granular deposition of LPS in the glomeruli. The results suggest that the early uptake of circulating LPS by cells of the reticulo-histiocytic system in liver and spleen, as well as by hepatocytes, is not mediated by HDL. However, HDL located in hepatocytes or present in the circulation of experimental mice seem to be eliminated through the bile and the urine, induced by LPS.


Intravaginal practices among young HIV-infected women in Lusaka, Zambia.
Intravaginal practices (IVP) are linked to bacterial vaginosis (BV), obstetric/gynecological complications, and HIV. Late adolescent and young adult (LAYA) women in Zambia have high rates of HIV. Adult and mature (AM) HIV-infected women in Zambia engage in IVP for hygiene, health, and sexuality reasons; however, to our knowledge, IVP use among LAYA women has not been examined. This study compares IVP use between LAYA and AM women to identify age-specific factors to target when developing IVP reduction interventions for LAYA women. LAYA (≤25 years; n = 24) and AM (>25 years; n=124) HIV-infected women completed self-administered demographic, HIV history, sexual risk factor, and IVP measures. LAYA and AM women were then compared. Number of sexual partners, sexual activity, or condom use did not differ between groups. Rates of IVP in the prior month with different products were similar, though LAYA women used soap more frequently (96% versus 74.2%, p = 0.034). LAYA women were more likely to use products for hygiene reasons (soap 83% versus 43%; cloth, paper, or wipes 50% versus 17%, p < 0.05); and AM women to use products to please sexual partners (cloth 20% versus 56%, p = 0.074). Interventions tailored to LAYA women may be needed to reduce IVP and subsequent BV as LAYA women may have different reasons for engaging in IVP, in comparison with AM women. Reduced IVP among LAYA women may decrease the risk for HIV transmission to sexual partners and newborns and is urgently needed in settings with high prevalence of IVP, BV, and HIV infections, such as Zambia.


Application Value of Serum Multi-Antibody Combined Detection in Differential Diagnosis and Typing of Lung Cancer.
One of the most prevalent malignant tumours is lung cancer. Circulating microRNAs (miRNAs) have shown to have significant promise for lung cancer diagnosis and prognosis, according to a growing body of research. The researchers wanted to explore if serum exosomal miR-1246 has any treatment significance in patients with non-small-cell lung cancer (NON-SCLC). Real-time PCR was used to determine the stage of exosomal miR-1246 serum expression in NON-SCLC patients. The researchers next looked into the link regarding exosomal miR-1246 serum stages and NON-SCLC prognosis. In NON-SCLC patients, exosomal miR-1246 serum appearance was considerably higher. According to a receiver operating characteristic (ROC) research, serum exosomal miR-1246 was effective in discriminating NON-SCLC patients from normal controls and non-malignant respiratory illness patients. Following treatment, the amount of serum exosomal miR-1246 reduced but increased in cases of recurrence. Furthermore, the level of serum exosomal miR-1246 was connected to distant metastases and TNM stages in a significant way. According to a survival analysis, cases with severe levels of exosomal miR-1246 serum had reduced overall or disease-free survival. The level of exosomal miR-1246 serum was found to be an autonomous predictive issue for NON-SCLC in multi-variate analysis. Finally, exosomal miR-1246 serum may be a useful prognosis biomarker for non-small-cell lung cancer.


A case of dobutamine-induced coronary arterial spasm with ST-segment elevation.
A 55-year-old Japanese woman demonstrated ST-segment elevation in leads I, aVL, and V3-V6 with chest pain both in an ergometer exercise test and on dobutamine stress echocardiography. Although the baseline coronary arteriogram revealed no organic stenosis, total occlusion of the distal portion of the posterolateral branch of the left circumflex artery was observed during dobutamine infusion with ST-segment elevation and chest pain. This is a rare case of documented dobutamine-induced coronary arterial spasm.


Evaluation of T2 values and apparent diffusion coefficient of the masseter muscle by clenching.
The aim of this study was to evaluate the changes in T2 values and apparent diffusion coefficient (ADC) in the masseter muscle by clenching in healthy volunteers. 37 volunteers were enrolled in the study. We measured bite force using pressure-sensitive paper and a T2 map. The ADC map was obtained at rest, during clenching, immediately after and 5 min after clenching. The spin-echo sequence was used to calculate T2, and single-shot spin-echo echo planar imaging was used to calculate the ADC. The motion-probing gradients (MPGs) were applied separately along the posterior-to-anterior (PA), right-to-left (RL) and superior-to-inferior (SI) directions, with b values of 0, 300 and 600 s mm(-2) in each direction. ADC-PA, ADC-RL, and ADC-SI values were obtained, and we calculated the ADC-iso for the mean diffusivity. There were no significant differences between the stronger and weaker sides of bite force before, during or 5 min after clenching for T2 and ADC. The bite force had little effect on these parameters; thus, we used the average of the two sides for the following analyses. Time course analysis of ADC-iso, ADC-PA, ADC-RL and ADC-SI demonstrated a marked increase after clenching and a rapid decrease immediately after clenching, although they did not completely return to the initial values; however, the change in ADC-RL was significantly greater than those in ADC-PA or ADC-SI (P<0.001 each). The changes in T2 were similar to those of ADC, although not as marked. ADC (especially ADC-RL) was altered by contraction of the masseter muscle.


Dressing with epigallocatechin gallate nanoparticles for wound regeneration.
Several reagents have been studied to overcome the problems encountered with antiseptic use, such as moderate cutaneous wound cytotoxicity and skin thinning. We successfully prepared a gelatin/chitosan/epigallocatechin gallate nanoparticle incorporated in a poly(γ-glutamic acid)/gelatin hydrogel, which comprised activated carbon fibers with gentamicin, to fabricate a sandwiched dressing to enhance wound regeneration. The inner layer of activated carbon fibers with gentamicin was designed to prevent bacterial infection, and the outer layer of gelatin/chitosan/epigallocatechin gallate nanoparticles incorporated in a poly(γ-glutamic acid)/gelatin hydrogel was designed to prevent inflammation and facilitate reepithelialization. An in vitro study demonstrated that the dressing effectively inhibited target microorganisms, and scanning electron microscope and confocal laser scanning microscope indicated that the nanoparticles were homogeneously dispersed and migrated into the hydrogel. The in vivo study reported that the sandwiched dressing, comprising the poly(γ-glutamic acid)/gelatin hydrogel, was easy to remove from the wound and facilitated wound tissue regeneration and accelerated healing process.


Molecular alterations in chronic ulcerative colitis-associated and sporadic hyperplastic polyps: a comparative analysis.
There is growing interest in the biological and molecular features and neoplastic potential of colonic hyperplastic polyps because of the recent finding of K-ras mutations in many of these lesions. Hyperplastic polyps may also develop in chronic ulcerative colitis (CUC), but it is unclear if these are biologically similar to the sporadic type. The aim of this study was to evaluate and compare the molecular profile of CUC-associated hyperplastic polyps with sporadic hyperplastic polyps of the colon. Thirty-nine hyperplastic polyps from 26 CUC patients, 39 sporadic hyperplastic polyps from 29 age- and sex-matched patients without CUC, and 26 colonic mucosal biopsies from 22 patients with CUC but without hyperplastic polyps were analyzed by polymerase chain reaction for loss of heterozygosity of APC, 3p, p53, and p16 and for mutations in codons 12, 13, and 61 of the K-ras gene. Immunohistochemical evaluations for the proliferation-associated nuclear peptide Ki67 (MIB-1) and p27 were also performed on a subset of hyperplastic polyps. CUC-associated hyperplastic polyps showed a proportion of genetic alterations (47%) similar to that of sporadic hyperplastic polyps (33%) (p > 0.05), and neither significantly differed from chronically inflamed mucosae in CUC patients without hyperplastic polyps. Furthermore, in a small group of CUC patients in which informative tissue was available from both their hyperplastic polyps and adjacent flat colitic mucosae, the polyps contained mutations that were not present in the underlying mucosa. Loss of heterozygosity of APC, 3p, p53, p16, and K-ras mutations were present in 21%, 40%, 27%, 20%, and 19% of CUC patients with hyperplastic polyps, respectively, and in 0%, 11%, 20%, 13%, and 13% of non-CUC patients with sporadic polyps, respectively. Both CUC-associated and sporadic hyperplastic polyps showed a substantial number of cases (46% and 64% of cases, respectively) with loss of p27 expression, and both types of lesions showed similar MIB-1 proliferation indices. These data suggest that CUC-associated hyperplastic polyps are genotypically similar to the sporadic type. This study adds to the expanding list of molecular alterations that have been discovered in hyperplastic polyps, and lends further support to the controversial theory that these lesions may have neoplastic potential.


Using X-mode L, R and O-mode reflectometry cutoffs to measure scrape-off-layer density profiles for upgraded ORNL reflectometer on NSTX-U.
The pre-existing ORNL scrape-off-layer (SOL) reflectometer that operated with the X-mode R-cutoff at 6-27 GHz to measure SOL density profiles on NSTX is being upgraded to be functional at the increased magnetic fields on NSTX-U spherical tokamak. Rather than increasing the operating frequencies to measure the higher X-mode R-cutoff frequencies on NSTX-U, it will be shown that the combined use of the X-mode R, L and O-mode cutoffs at 6-27 GHz can obtain the desired SOL density profiles. The potential capabilities and obstacles of this technique to measure SOL density profiles and possibly SOL magnetic field profiles on NSTX-U will be discussed.


Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi.
Lyme disease is a tick-borne illness caused by the spirochete Borrelia burgdorferi. Although antibiotic therapy is usually effective early in the disease, relapse may occur when administration of antibiotics is discontinued. Studies have suggested that resistance and recurrence of Lyme disease might be due to formation of different morphological forms of B. burgdorferi, namely round bodies (cysts) and biofilm-like colonies. Better understanding of the effect of antibiotics on all morphological forms of B. burgdorferi is therefore crucial to provide effective therapy for Lyme disease. Three morphological forms of B. burgdorferi (spirochetes, round bodies, and biofilm-like colonies) were generated using novel culture methods. Minimum inhibitory concentration and minimum bactericidal concentration of five antimicrobial agents (doxycycline, amoxicillin, tigecycline, metronidazole, and tinidazole) against spirochetal forms of B. burgdorferi were evaluated using the standard published microdilution technique. The susceptibility of spirochetal and round body forms to the antibiotics was then tested using fluorescent microscopy (BacLight™ viability staining) and dark field microscopy (direct cell counting), and these results were compared with the microdilution technique. Qualitative and quantitative effects of the antibiotics against biofilm-like colonies were assessed using fluorescent microscopy and dark field microscopy, respectively. Doxycycline reduced spirochetal structures ∼90% but increased the number of round body forms about twofold. Amoxicillin reduced spirochetal forms by ∼85%-90% and round body forms by ∼68%, while treatment with metronidazole led to reduction of spirochetal structures by ∼90% and round body forms by ∼80%. Tigecycline and tinidazole treatment reduced both spirochetal and round body forms by ∼80%-90%. When quantitative effects on biofilm-like colonies were evaluated, the five antibiotics reduced formation of these colonies by only 30%-55%. In terms of qualitative effects, only tinidazole reduced viable organisms by ∼90%. Following treatment with the other antibiotics, viable organisms were detected in 70%-85% of the biofilm-like colonies. Antibiotics have varying effects on the different morphological forms of B. burgdorferi. Persistence of viable organisms in round body forms and biofilm-like colonies may explain treatment failure and persistent symptoms following antibiotic therapy of Lyme disease.


Uterine leiomyosarcoma and endometrial stromal sarcoma: lymph node metastases and sites of recurrence.
This study was undertaken to examine the incidence and conditions under which lymph node metastases are present and patterns of recurrence in women with uterine leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS), excluding malignant mixed mesodermal tumors. From 1981 through 1991, 21 women with LMS and 10 women with ESS were treated. Retroperitoneal lymph node dissections were performed in 15 women with LMS and 7 women with ESS. In the women with LMS, 4/15 (26.7%) had lymph node metastases; in each there was disseminated intra-abdominal disease. In the 7 women with ESS, there were no lymph node metastases present. Ten women (47%) with LMS developed recurrences, and 3 (14%) had persistent disease. In the 10 women with ESS, 3 (30%) had recurrences, and 1 (10%) had persistent disease. In total, recurrences involved the lung in 84% of cases. Of the 13 women with recurrences, 7 had undergone lymph node sampling, and all were negative; 4 additional women had no evidence of adenopathy on abdominal-pelvic CT scan. Lymph node metastases were found only with extrauterine disease, and in all of these cases there was rapid progression of the sarcoma. Women without extrauterine disease did not have lymph node metastases detected; however, there was still a high rate (40%) of distant failure. Knowledge of lymph node status had minimal impact on the clinical management of women with uterine LMS and ESS.


Role of interferon in natural kill of HSV-1-infected fibroblasts.
The production of interferon during natural killer (NK) assays against HSV-1-infected fibroblasts (NK(HSV-1)) was studied to determine whether this interferon was responsible for inducing the preferential lysis of herpes-virus-infected target cells over uninfected target cells. The interferon produced during NK(HSV-1) assays was analyzed and found to have the properties of HU-IFN-alpha. Little or no IFN was produced during NK assays against uninfected fibroblasts (NK(FS)) or K562 (NK(K562)) cells. Although the appearance of interferon in the culture supernatants seemed to parallel the development of cytotoxicity during NK(HSV-1) assays, the levels of cytotoxicity and IFN generated did not correlate, arguing against a strict quantitative dependence of cytotoxicity upon IFN production. NK(K562) and NK(FS) cytotoxicity developed with little or no production of IFN. When IFN-pretreated effector cells were used, there was still a preferential lysis of infected over uninfected target cells. This preferential lysis by IFN-treated effector cells of infected over uninfected targets was seen as early as 2 hr into the assay. Anti-IFN antibodies added to the NK assays, although neutralizing all the IFN produced during the assays, had no effect on NK(FS) or NK(K562) cytotoxic activity and caused a slightly reduction of NK(HSV-1) activity only in one of three experiments. We conclude that although IFN is generated during NK(HSV-1) assays, this IFN cannot solely account for the increased lysis of infected over uninfected cells and that NK(HSV-1) activity is in some other way dependent on the virus infection.


One-dimensional and multichannels multi-imaging x-ray streak camera for imploded core plasma of shell-cone target.
Recently one-dimensional and multichannels multi-imaging x-ray streak camera (1D+McMIXS) has been proposed as an ultrafast diagnostic tool for imploded core plasma of shell-cone target. This diagnostic system can provide much more information of core plasma dynamics, such as the shell trajectory before the maximum compression, two dimensional (2D) x-ray images, and 2D map of electron temperature. The 1D+McMIXS was used in an implosion experiment of a shell target with a cone for fast ignition at Gekko XII laser facility. The interaction between the core plasma and the tip of the cone was observed and revealed some detailed structures. A series of time-resolved 2D x-ray images were reconstructed and a nominal temperature evolution was also mapped.


Minimally invasive injection laryngoplasty in the management of unilateral vocal cord paralysis after video-assisted mediastinal lymph adenectomy.
Video-assisted mediastinal lymphadenectomy (VAMLA) is a valuable tool for invasive staging of the mediastinum. Unilateral vocal cord paralysis (UVCP) may occur in patients following VAMLA and may result in secretion retention within the lungs, atelectasis and associated infectious situations such as pneumonia. Minimally invasive injection laryngoplasty (ILP) is the treatment of choice in UVCP. To evaluate the efficacy and success of acute minimally invasive injection laryngoplasty for patients with UVCP following VAMLA. Patients with the symptom of dysphonia following VAMLA were reviewed. All of the patients had UVCP according to the video laryngoscopy examination and had symptoms of aspiration and ineffective coughing. The Voice Handicap Index (VHI) questionnaire and maximum phonation time (MPT) were measured. Minimally invasive ILP was performed under general anesthesia with 1 cm of hyaluronic acid. There were 525 consecutive non-small cell lung cancer (NSCLC) patients who underwent VAMLA. Five (0.95%) of the patients had UVCP and were suffering from aspiration during oral intake and ineffective coughing reflex. Maximum phonation time (MFT) was measured before and after ILP, and the results were 7.1 ±1.6 and 11.1 ±2.3 s, respectively (p < 001). The Voice Handicap Index-10 (VHI-10) score was 30.4 ±4.7 and 13.4 ±3.5 (p < 0.01), respectively. Patients underwent surgical lung resection. There was no morbidity or mortality. Unilateral vocal cord paralysis may occur as a complication of VAMLA. ILP may be an active tool for treating UVCP before anatomical lung resection to avoid potential morbidities. Successful management of this complication with multidisciplinary team work may encourage the use of VAMLA more frequently.


Recovery of circadian melatonin rhythm after a melatonin holiday in daytime haemodialysis patients on long-term exogenous melatonin.
The effects of exogenous melatonin on sleep diminish after its long-term use in haemodialysis patients. Our aim was to determine whether melatonin levels accumulate after chronic (at least three months) use of exogenous melatonin, 5 mg daily, and whether discontinuation of this treatment improves endogenous melatonin production and improves the circadian sleep-wake rhythm. In this case series, stable haemodialysis patients discontinued their chronic exogenous melatonin usage for seven days and melatonin concentrations in saliva were analysed. The primary endpoint was recovery of a normal circadian melatonin rhythm. Secondary endpoints were the effects on melatonin pharmacokinetics and sleep parameters. At day three after discontinuation the normal circadian melatonin rhythm recovered in the two patients who discontinued the treatment for the full week. They also had an effective maximum trough level of melatonin. Discontinuing melatonin seems to result in recovery of the circadian rhythm, based on achievement of effective melatonin thresholds. Further research is necessary to investigate whether sleep parameters improve after a drug holiday.most appropriate treatment.


High-performance gas-phase adsorption of benzene and toluene on activated carbon: response surface optimization, reusability, equilibrium, kinetic, and competitive adsorption studies.
In recent years, volatile organic compounds (VOCs) have become a group of major pollutants that endanger human health and the ecological environment. The main purpose of this study was to investigate the gas-phase adsorption processes of benzene and toluene, which are important VOCs, on the activated carbon (AC) produced from Elaeagnus angustifolia seeds by physical activation method. In this context, the central composite design (CCD) approach-based response surface methodology (RSM) was applied to examine and optimize the effects of process parameters on the adsorption of benzene and toluene by AC adsorbent. The characterization of the produced AC was performed by the Brunauer-Emmett-Teller surface area, scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. The optimum process parameters were achieved (adsorption time of 74.98 min, initial benzene concentration of 16.68 ppm, and temperature of 26.97 °C, and adsorption time of 73.26 min, initial toluene concentration of 18.46 ppm and temperature of 29.80 °C) for benzene and toluene, respectively. The maximum adsorption capacities of benzene and toluene on AC were determined to be 437.36 and 512.03 mg/g, respectively, under optimum parameters. The adsorption process kinetics and equilibrium isotherms were also evaluated. Besides, AC reusability studies were performed five times for the gas-phase adsorption and desorption of benzene and toluene. After five cycles, it was observed that the benzene and toluene adsorption capacity of the AC decreased slightly by 8.10% and 7.42%, respectively. The results revealed that the produced AC could be utilized successfully for the removal of benzene and toluene in the gas-phase adsorption systems because of its high surface area, high adsorption capacity, and high reusability performance. Furthermore, the adsorption processes of benzene and toluene were investigated, both sole components and in a binary mixture. It was concluded that the adsorption behaviors of benzene and toluene against AC were quite different when they were in the competition (in a binary mixture) and without competition (sole components). Graphical abstract.


[Implementation of a psychological support program for children with cancer in Poland. Preliminary report].
Intensive chemotherapy programme in children with cancer may result in psychological mal adjustment. Treatment facilities as well as psychological support are of great importance to minimize these side effects. In 1998 the programme of psychological support was introduced in 7 Polish paediatric haematology / oncology centres. Psychological adjustment of patients treated in each centre was examined 5 yrs after the termination of therapy. At the same time children with new diagnosis of cancer were monitored psychologically along with the psychological support programme. Psychological status of each patient was examined with the following tests: Cattell's questionnaires (CPQ, HSPQ), Manifest Anxiety Scale, Spielberger's inventories (STAI, STAIC), Wechsler Intelligence Scale. The programme of psychological support was based on guidelines of SIOP Psychosocial Committee and included such elements as informing about diagnosis and treatment, explaining any doubt, maintaining an open communication, educational care in the periods of treatment, encouraging to activity even during periods of discomfort. The analysis showed that most of the participating centres could only provide some elements of the support programme. The main problem was to convince medical staff to inform children on diagnosis and treatment plans. Preliminary results of the study indicate that full psychological support for children with cancer and their families from the beginning of therapy can result in improvement in psychological adjustment. During the ensuing period, patients and their parents appreciate the possibilities to contact a psychologist.


Preoperative risk factors for mortality after biventricular assist device implantation.
A right ventricular assist device is a treatment option for patients with severe right ventricular failure after left ventricular assist device (LVAD) implantation. Recognition of risk factors for mortality after biventricular assist device (BiVAD) implantation is important for patient selection and optimal outcomes. We reviewed our experiences between 1991 and 2005 in 44 patients who were supported by both an LVAD and a right ventricular assist device. Thirteen patients (30%) survived until heart transplantation, and 31 patients (70%) died while on support. The multivariate analysis shows that post-LVAD extracorporeal membrane oxygenation and worsening renal function are associated with the highest postoperative mortality. The univariate analysis also included previous thoracic surgery and ischemic cardiomyopathy as potential preoperative indicators for poor outcome after BiVAD implants. No differences were observed in the rates for the need of preoperative support with a ventilator, an intra-aortic balloon pump, or extracorporeal membrane oxygenation, or in the rates of postoperative complications between survivors and nonsurvivors. BiVAD implantation remains one of the challenges in treating severe heart failure. Previous cardiac surgery, elevated creatinine, and post-LVAD extracorporeal membrane oxygenation were risk factors for mortality after BiVAD implantation. Dialated Cardiomyopathy on the other hand was associated with a more favorable outcome.


[The evolution of the Hippocratic oath].
The oath was the result of the new course of the Greek philosophy, following the thought of Anaxagoras of Clazomenes, who joined physis and techne in a rational sequence of observations. Thus, the oath lay the foundation for medical schools (relationship teacher-pupils) and for medicine (relationship physician-patient); the rules (including prohibitions) of the oath have been the rules of medicine for centuries, present in other rules, like the Constitutiones melphitanae of Frederich 2nd or the prayer of Maimonides (which is a forged manuscript, made in the XVIII century, important for the contents because it is a more modern version of an oath). Finally in recent years the World Health Organization and National Medical Councils with public declarations or deontological codes have revised the principles of medical ethics twenty-five centuries after the Hippocratic oath.


Safety and efficacy of the potassium-titanyl-phosphate laser and photoselective vaporization of the prostate for benign prostatic hyperplasia.
The currently commercially available 80-W potassium-titanyl-phosphate laser used for photoselective vaporization of the prostate in men with lower urinary tract symptoms and benign prostatic hyperplasia (BPH) is a safe and effective therapeutic alternative for a wide spectrum of prostate sizes and configurations. Efficacy data from multicenter prospective studies, comparative studies against other interventions, and single-center long-term outcomes suggest the efficacy to be at least equivalent to that of transurethral resection of the prostate, with a very good safety profile. New technological developments promise to further enhance the utility of this laser for application in BPH and urology.


Comparative evaluation of laser-microtextured implant versus machined collar implant for soft and hard tissue attachment: A clinical and radiological study.
Various mechanical modifications in the collar region of endosseous implants is a challenge for better performance and osseointegration. Here is a comparative evaluation being carried out to find out the effect of the machined collar (MC) and Laser-Lok (LL)-modified titanium implants on the success of implants being commonly advocated in partially edentulous among serving personnel and their families. Twenty-four patients with appropriate inclusion and exclusion criteria were selected for placement of Biohorizons MC and LL implants in 12 cases each. Aseptic surgical procedure was followed for implant surgery, and clinical parameters such as clinical attachment loss, pocket depth (PD), bleeding on probing, and plaque index (PI), mobility parameters estimated by Periotest value, and radiographic assessment of crestal bone loss (CBL) at interval of 6 months and 1 year were recorded and compared by statistical analysis. Intragroup comparison at 6 and 12 months period for all the parameters were nonsignificant except CBL in Group A (CBL-MC) with 12 cases shows a mean of 0.917 and 1.500, respectively, standard deviation difference = 0.477 (significant) with P < 0.05. Similar significant difference in CBL was observed with superior result in LL implants. The presence of LASER textured with microgrooves on the collar of the implants did not increase the PI and sulcular bleeding index. The probing PD was much less as observed in the group of LASER-treated implants in comparison with that of MC group. LL implant had an edge over MC proving success of the laser treatment on collars of implants.


Subchronic exposure to chlorpyrifos affects energy expenditure and detoxification capacity in juvenile Japanese quails.
Effects of pesticides on non-target organisms have been studied in several taxa at different levels of biological organization, from enzymatic to behavioral responses. Although the physiological responses may be associated with higher energy costs, little is known about metabolic costs of pesticide detoxification in birds. To fill this gap, we exposed orally (diet) 15-d old Coturnix coturnix japonica individuals to sublethal doses of chlorpyrifos (10 and 20 mg active ingredient/kg dry food) for four weeks. Carboxylesterase (CbE), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) activities were periodically measured in multiple tissues along with measurements of resting (RMR) and maximum metabolic rates (M(sum)). Furthermore, glucuronic acid in bird excreta was also assessed at the end of the trial. While CbE and BChE activities were inhibited by chlorpyrifos in all tissues during the third and fourth weeks following pesticide treatment, AChE activity was unaffected. At this sampling times, both M(sum) and RMR expansibility decreased. These results suggest that the exposure to chlorpyrifos caused a negative effect on aerobic performance. Additionally, excretion rate of glucuronic acid was up to 2-fold higher in the 20-mg/kg group than in the control and 10-mg/kg chlorpyrifos groups. The inhibition of CbE and BChE activities corroborated that these enzymes are fulfilling their role as bioscavengers for organophosphate pesticides, decreasing its concentration and thus protecting AChE activity against inhibition by chlorpyrifos.


Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy.
As the application of core needle biopsy (CNB) in evaluating thyroid nodules rises in clinical practice, the 2023 Korean Thyroid Association Management Guidelines for Patients with Thyroid Nodules have officially recognized its value for the first time. CNB procures tissue samples preserving both histologic structure and cytologic detail, thereby supplying substantial material for an accurate diagnosis and reducing the necessity for repeated biopsies or subsequent surgical interventions. The current review introduces the risk of malignancy within distinct diagnostic categories, emphasizing the implications of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on these malignancy risks. Prior research has indicated diagnostic challenges associated with follicular-patterned lesions, resulting in notable variation within indeterminate diagnostic categories. The utilization of mutation-specific immunostaining in CNB enhances the accuracy of lesion classification. This review underlines the essential role of a multidisciplinary approach in diagnosing follicular-patterned lesions and the potential of mutation-specific immunostaining to strengthen diagnostic consensus and inform patient management decisions.


Double-blind evaluation of naftidrofuryl in treating elderly confused hospitalised patients.
In a double-blind comparison between naftidrofuryl and placebo, naftidrofuryl-treated patients improved significantly on scales completed by the nurse, occupational therapist and physician. No improvement was found for placbo-treated patients. When the response to each treatment was compared, naftidrofuryl was found to be significantly better than placebo on both nurse and physician assessment. There was considerable variation between assessors which suggests that they were measuring different aspects of the patients' condition. There was also considerable variation in patient response, some improved on naftidrofuryl and some deteriorated; some improved on placebo and some deteriorated. However, overall it would seem that patients admitted to hospital with confusional states benefit from treatment with naftidrofuryl.


Role of Interleukin 28B Polymorphisms in Response to Interferon Based Therapy for Hepatitis C Virus Clearance.
Interleukin-28B (IL28B) locus on a human chromosomal region mapped to 19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV) infection the IL28B has a promising role in deciding the consequence of infection for spontaneous clearance of viruses or causing chronic liver infection. Treatment of chronic hepatitis C includes use of direct acting antivirals, Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. Also, interferon free regimens are suggested to be useful in resistant patients. Numerous reports including Genome-Wide Association Studies (GWAS), comprehensive meta-analysis and independent case-control studies in different population have revealed the association between certain Il-28B polymorphisms and response to the PEGIFN- RBV therapy in patients infected with HCV. We searched all peer-reviewed relevant and recent literature manually for the present review. The GWAS studies have revealed an important role of IL28B in HCV infection, which was supported by many independent studies and meta-analysis by different groups in different ethnicities. IL28B genotyping may be use as predictors of response for IFN-based therapy and personalized treatment of hepatitis C patient.


Crassulacean acid metabolism guard cell anion channel activity follows transcript abundance and is suppressed by apoplastic malate.
Plants utilising crassulacean acid metabolism (CAM) concentrate CO2 around RuBisCO while reducing transpirational water loss associated with photosynthesis. Unlike stomata of C3 and C4 species, CAM stomata open at night for the mesophyll to fix CO2 into malate (Mal) and store it in the vacuole. CAM plants decarboxylate Mal in the light, generating high CO2 concentrations within the leaf behind closed stomata for refixation by RuBisCO. CO2 may contribute to stomatal closure but additional mechanisms, plausibly including Mal activation of anion channels, ensure closure in the light. In the CAM species Kalanchoë fedtschenkoi, we found that guard cell anion channel activity, recorded under voltage clamp, follows KfSLAC1 and KfALMT12 transcript abundance, declining to near zero by the end of the light period. Unexpectedly, however, we found that extracellular Mal inhibited the anion current of Kalanchoë guard cells, both in wild-type and RNAi mutants with impaired Mal metabolism. We conclude that the diurnal cycle of anion channel gene transcription, rather than the physiological signal of Mal release, is a key factor in the inverted CAM stomatal cycle.


Arginase inhibitor in the pharmacological correction of endothelial dysfunction.
THIS PAPER IS ABOUT A WAY OF CORRECTION OF ENDOTHELIAL DYSFUNCTION WITH THE INHIBITOR OF ARGINASE: L-norvaline. There is an imbalance between vasoconstriction and vasodilatation factors of endothelium on the basis of endothelial dysfunction. Among vasodilatation agents, nitrogen oxide plays the basic role. Amino acid L-arginine serves as a source of molecules of nitrogen oxide in an organism. Because of the high activity of arginase enzyme which catalyzes the hydrolysis of L-arginine into ornithine and urea, the bioavailability of nitrogen oxide decreases. The inhibitors of arginase suppress the activity of the given enzyme, raising and production of nitrogen oxide, preventing the development of endothelial dysfunction.


Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis.
To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients. In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score >10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score >10; additional visits and treatment acceleration were at the discretion of usual care providers and patients. Coprimary end points were feasibility, assessed by rate of treatment acceleration conditional on CDAI score >10, and achievement of low disease activity (LDA; CDAI score ≤10) by an intent-to-treat analysis. A total of 14 practice sites per study arm were included (246 patients receiving treat-to-target and 286 receiving usual care). The groups had similar baseline demographic and clinical characteristics. Rates of treatment acceleration (treat-to-target 47% versus usual care 50%; odds ratio [OR] 0.92 [95% confidence interval (95% CI) 0.64, 1.34]) and achievement of LDA (treat-to-target 57% versus usual care 55%; OR 1.05 [95% CI 0.60, 1.84]) were similar between groups. Treat-to-target providers reported patient reluctance and medication lag time as common barriers to treatment acceleration. This study is the first to examine the feasibility and efficacy of a treat-to-target approach in typical US rheumatology practice. Treat-to-target care was not associated with increased likelihood of treatment acceleration or achievement of LDA, and barriers to treatment acceleration were identified.


Effects of monoclonal antibody directed to LeY on implantation in the mouse.
The role of carbohydrates in embryo implantation in the mouse was investigated using an embryo transfer model and a blastocyst-uterine epithelial cell co-culture system. The monoclonal antibody (mAb) AH6 directed to LeY oligosaccharide (Fuc alpha1-2 Gal beta 1-4 [Fuc alpha1-3] GlcNAc) and other three mAbs directed to carbohydrates whose structures are closely related to LeY were used to show the effect of carbohydrate specificity on implantation. In the embryo transfer model, donor blastocysts (4 days post-coitus) were pretreated with mAb AH6 (experimental) or other mAbs (control) and transferred into one uterine horn of a recipient. The implantation rate was checked after 5 days. Implantation was significantly inhibited by mAb AH6 pretreatment, and inhibition was not observed in control groups. In the co-culture system, the attachment and outgrowth rate of blastocysts on the surface of uterine epithelial cells was significantly inhibited when monolayer epithelial cells or blastocysts were pretreated with mAb AH6. The most obvious effect of mAb AH6 was obtained during 2-4 h co-incubation. No inhibition was observed in the control groups. It was, therefore, concluded that oligosaccharide LeY recognized by mAb AH6 plays an essential role at the initial stage of implantation. It may act as a mediator molecule for adhesion between the surface of blastocyst and epithelial cell, and its function is carbohydrate-specific.


Septic syndrome and septic shock in the wounded treated at the Split Clinical Hospital Intensive Care Unit.
A retrospective study on the occurrence of septic syndrome and septic shock, as well as multiorgan failure, in the wounded at the Split Clinical Hospital Intensive Care Unit (ICU). From 1991 to 1995, 257 wounded persons were treated at the Split Clinical Hospital ICU. Criteria for septic syndrome included evident infection, body temperature > 38 degrees C or < 30.5 degrees C, leukocytosis or leukopenia, thrombocytopenia, as well as dysfunction of one organ. The criterion for septic shock was septic syndrome with hypotonia. Fifteen patients with septic syndrome and 9 patients with septic shock were admitted and treated at the ICU. Septic syndrome developed in 17 patients and septic shock in 16 patients at the ICU. Acute respiratory distress syndrome developed in 16, renal insufficiency in 26, gastrointestinal disorders in 6, hepatic disorders in 4, hematologic disorders in 13, and central nervous system dysfunction in 17 patients. Twenty-eight percent of patients died in septic syndrome, and 74% died in septic shock. Septic syndrome and septic shock were the most common causes of death in wounded persons treated at Split Clinical Hospital ICU. At the earliest phase the main cause of death was refractory hypotension, and at the later stage the main cause of death was multiorgan failure.


Photoinduced Palladium-Catalyzed Intermolecular Radical Cascade Cyclization of N-Arylacrylamides with Unactivated Alkyl Bromides.
A mild visible-light-induced Pd-catalyzed intermolecular radical cascade reaction of N-arylacrylamides with unactivated alkyl bromides is disclosed. Photoexcited Pd complexes transfer a single electron in this protocol, and hybrid alkyl Pd-radical species are involved as the key reaction intermediates. Sophisticated bioactive oxindole derivatives bearing various substituents and substitution patterns can be efficiently afforded through this approach.


Collective neurodynamic optimization for economic emission dispatch problem considering valve point effect in microgrid.
The economic emission dispatch (EED) problem aims to control generation cost and reduce the impact of waste gas on the environment. It has multiple constraints and nonconvex objectives. To solve it, the collective neurodynamic optimization (CNO) method, which combines heuristic approach and projection neural network (PNN), is attempted to optimize scheduling of an electrical microgrid with ten thermal generators and minimize the plus of generation and emission cost. As the objective function has non-derivative points considering valve point effect (VPE), differential inclusion approach is employed in the PNN model introduced to deal with them. Under certain conditions, the local optimality and convergence of the dynamic model for the optimization problem is analyzed. The capability of the algorithm is verified in a complicated situation, where transmission loss and prohibited operating zones are considered. In addition, the dynamic variation of load power at demand side is considered and the optimal scheduling of generators within 24 h is described.


Nivolumab for the treatment of urothelial cancers.
Advanced urothelial cancer patients had limited therapeutic options following failure of platinum-based chemotherapy. The recognition that anti-PD1/PDL1 immune checkpoint inhibitors lead to dramatic and durable responses in a subset of patients has transformed the therapeutic landscape of these cancers. Since May 2016, five agents targeting this pathway have been approved by the US FDA, including the PD-1 inhibitor nivolumab. Areas covered: The purpose of this paper was to review the safety, activity and efficacy of nivolumab, an anti-PD1 checkpoint inhibitor for the treatment of locally-advanced or metastatic urothelial cancers. Future therapeutic perspectives were also discussed. Expert commentary: Nivolumab is one of five anti-PD1/PDL1 checkpoint inhibitors approved for treatment of advanced urothelial cancers. While durable responses can be observed, only 15 - 24% of patients are likely to respond. To date, there are no validated biomarkers, including PDL1 expression, which might accurately identify patients who are likely to respond. Many different biomarkers are currently under active investigation. Future direction for therapeutic development is likely to involve combination therapies with PD1/PDL1 agent as the therapeutic backbone.


Optimization of accessible catalase activity in polyacrylamide gel-immobilized Saccharomyces cerevisiae.
The permeabilization of Saccharomyces cerevisiae (baker's yeast), either before or after immobilization in polyacrylamide gel (PAG), has been examined as a means to increase the catalase activity of PAG-immobilized yeast cells. Prior permeabilization of the cells resulted in large losses of catalase activity during immobilization, but permeabilization after immobilization produced increases in the catalase activity of yeast/PAG particles. A dependence of the accessible catalase activity on the concentration of polyacrylamide in permeabilized yeast/PAG particles, and on the method of permeabilization of the immobilized cells, was observed. Optimal levels of stable catalase activity (1000-2000 IU/g PAG particles; ca. 5%-10% of total available activity) were obtained by immobilizing yeast cells (0.5 g wet cells/mL gel) in 10% (w/v) PAG, followed by permeabilization of the entrapped cells with either cetyltrimethylammonium bromide, Triton X-100 and one freeze-thaw, or five freeze-thaw cycles.


Favorable Outcomes in Blunt Chest Injury with Noninvasive Bi-Level Positive Airway Pressure Ventilation.
Recent clinical research in patients with blunt chest injury has focused on the benefits of surgical fixation of rib fractures. Noninvasive ventilation (NIV) has been demonstrated to prevent the need for intubation and ventilation in posttraumatic respiratory failure. The preemptive use of NIV in patients with rib fractures has not been extensively studied. Our study evaluated the outcomes of patients with ≥3 rib fractures and hospitalized for ≥ 4 days. Seventy-one patients treated with NIV were compared with 270 patients without NIV. NIV patients were older (65.8 vs 56.5 years) had more rib fractures (6.25 vs 5.32) and a higher body mass index (31 vs 27.8) than the comparison group, P < 0.05, but did not have an increased mortality or incidence of respiratory failure. NIV patients did have a statistically significant increase in length of stay compared to control (12.8 vs 8.8, P < 0.05). In the total sample, worse clinical outcomes were associated with older age, increased number of and bilateral rib fractures, higher Injury Severity Score, lower Glasgow Coma Scale, and higher body mass index. Outcomes in the most severely injured group of patients treated with NIV were comparable to other studies using surgical fixation of rib fractures and epidural pain control.


Assessing the failing systemic right ventricle.
The purpose of this article is to address main clinical issues and the way to assess right ventricular (RV) function of adult patients with transposition complexes and systemic RV failure. Echo, cardiopulmonary exercise test, radionuclide ventriculography, cardiac magnetic resonance imaging, multislice computed tomography, and cardiac catheterization may be performed in adult patients with transposition complexes to evaluate clinical status and RV function. Echo is an everyday clinical tool that can give valuable information on RV function, tricuspid regurgitation, concomitant lesions, or postoperative complications. Cardiac magnetic resonance is the gold standard in the estimation of RV volumes and function. Cardiopulmonary exercise test can provide objective evaluation of patients' clinical status. Other imaging modalities are useful when appropriate. In conclusion, for all transposition complexes adult patients should undergo a regular follow-up to recognize early signs of systemic RV failure.


Stability of hydroperoxide lyase activity from Amaranthus tricolor (Amaranthus mangostanus L.) leaves: influence of selected additives.
Hydroperoxide lyase (HPL) has potential value for the flavour additive industry. Currently, the production and application of HPL suffer from stability problems. The objective of this study was to investigate the stabilisation of HPL preparation from Amaranthus tricolor leaves by the addition of selected chemical additives. Amaranthus tricolor leaves were identified as a particularly rich source of 13-HPL activity. The addition of 100 g L(-1) sucrose and trehalose to microsomal HPL prior to lyophilisation could retain nearly 100% enzymatic activity, compared to only 20% for the lyophilised control. The lyophilised microsomal HPL containing sucrose maintained full activity for even 40 days storage at -20 degrees C. For HPL solution, glycerol was effective for long-term stability at -20 degrees C. Moreover, poyols (sucrose and trehalose) and amino acid (glycine) enhanced the thermostability of HPL, while KCl and polyol mannitol decreased the thermostability of HPL. The flavour-producing enzyme HPL, found in the leaves of Amaranthus tricolor, was stabilised by the addition of chemical additives.


[Correlation between the circulation of the hemispheres and brain stem regions, the peripheral circulation and bioelectrical activity of the brain in the dynamics of the acute period of cranio-cerebral injury].
Polygraphic recording of rheoencephalography, rheovasography and EEG was used for a dynamic examination of 45 patients with severe (28 cases) and moderate (17 cases) craniocerebral injuries. In 13 patients, of the former group intracranial haematomas were noted, in 15--contusion foci. A method of rheoencephalography recording from the brain stem with the aid of a basal electrode was developed, and it permitted to obtain valuable information on the degree of the haemodynamic shifts in the brain stem. A persistent reduction of the CBF was observed in the basalocciptal lead found to be proportional to the severity of the craniocerebral injury. The results of mathematical processing of the obtained data demonstrated a clear correlation of the clinical state of the patient, the bioelectrical activity of the brain and the indices of the tonicity and blood filling of the cerebral vessels: along with re-establishment of the normal alpha-rhythm and reduction of a slow pathological activity of the EEG, a clear increase in the cerebral blood flow value was observed.


Extracellular and membrane-bound proteases from Bacillus subtilis.
Bacillus subtilis YY88 synthesizes increased amounts of extracellular and membrane-bound proteases. More than 99% of the extracellular protease activity is accounted for by an alkaline serine protease and a neutral metalloprotease. An esterase having low protease activity accounts for less than 1% of the secreted protease. These enzymes were purified to homogeneity. Molecular weights of approximately 28,500 and 39,500 were determined for the alkaline and neutral proteases, respectively. The esterase had a molecular weight of approximately 35,000. Amino-terminal amino acid sequences were determined, and the actions of a number of inhibitors were examined. Membrane vesicles contained bound forms of alkaline and neutral proteases and a group of previously undetected proteases (M proteases). Membrane-bound proteases were extracted with Triton X-100. Membrane-bound alkaline and neutral proteases were indistinguishable from the extracellular enzymes by the criteria of molecular weight, immunoprecipitation, and sensitivity to inhibitors. The M protease fraction accounted for approximately 7% of the total activity in Triton X-100 extracts of membrane vesicles. The M protease fraction was partially fractionated into four species (M1 through M4) by ion-exchange chromatography. Immunoprecipitation and sensitivity to inhibitors distinguished membrane-bound alkaline and neutral proteases from M proteases. In contrast to alkaline and neutral proteases, proteases M2 and M3 exhibited exopeptidase activity.


Genome Sequence of Flavobacterium akiainvivens IK-1T, Isolated from Decaying Wikstroemia oahuensis, an Endemic Hawaiian Shrub.
Flavobacterium spp. have been cultivated from diverse aquatic and terrestrial habitats. F. akiainvivens IK-1(T) was cultivated from decaying wood of Wikstroemia oahuensis, an endemic Hawaiian shrub. The strain's genome sequence may provide insights into niche adaptation and evolution of the genus in a mid-ocean archipelago.


The association between whole body sagittal balance and risk of falls among elderly patients seeking treatment for back pain.
The objective of this study was to assess the association between whole body sagittal balance and risk of falls in elderly patients who have sought treatment for back pain. Balanced spinal sagittal alignment is known to be important for the prevention of falls. However, spinal sagittal imbalance can be markedly compensated by the lower extremities, and whole body sagittal balance including the lower extremities should be assessed to evaluate actual imbalances related to falls. Patients over 70 years old who visited an outpatient clinic for back pain treatment and underwent a standing whole-body radiograph were enrolled. Falls were prospectively assessed for 12 months using a monthly fall diary, and patients were divided into fallers and non-fallers according to the history of falls. Radiological parameters from whole-body radiographs and clinical data were compared between the two groups. A total of 144 patients (120 female patients and 24 male patients) completed a 12-month follow-up for assessing falls. A total of 31 patients (21.5%) reported at least one fall within the 12-month follow-up. In univariate logistic regression analysis, the risk of falls was significantly increased in older patients and those with more medical comorbidities, decreased lumbar lordosis, increased sagittal vertical axis, and increased horizontal distance between the C7 plumb line and the centre of the ankle (C7A). Increased C7A was significantly associated with increased risk of falls even after multivariate adjustment. Whole body sagittal balance, measured by the horizontal distance between the C7 plumb line and the centre of the ankle, was significantly associated with risk of falls among elderly patients with back pain.Cite this article: J. Kim, J. Y. Hwang, J. K. Oh, M. S. Park, S. W. Kim, H. Chang, T-H. Kim. The association between whole body sagittal balance and risk of falls among elderly patients seeking treatment for back pain. Bone Joint Res 2017;6:-344. DOI: 10.1302/2046-3758.65.BJR-2016-0271.R2.


Palliative radiotherapy: current status and future directions.
For nearly 100 years, palliative radiotherapy has been a time-efficient, effective treatment for patients with metastatic or advanced cancer in any area where local tumors are causing symptoms. Short courses including a single fraction of radiotherapy may be effective for symptom relief with minimal side effects and maximization of convenience for patient and family. With recent advances in imaging, surgery, and other local therapies as well as systemic cancer therapies, palliative radiotherapy has been used frequently in patients who may not yet have symptoms of advanced or metastatic cancer. In this setting, more prolonged radiotherapy courses and advanced radiotherapy techniques including intensity-modulated radiotherapy (IMRT) or stereotactic radiotherapy (SRT) may be useful in obtaining local control and durable palliative responses. This review will explore the use of radiotherapy across the spectrum of patients with advanced and metastatic cancer and delineate an updated, rational approach for the use of palliative radiotherapy that incorporates symptoms, prognosis, and other factors into the delivery of palliative radiotherapy.


Bias in visual attention behavior in a normal school-aged population.
Hemi-field visual-spatial attention was studied on a timed letter cancellation task in proficient readers from 7th to 9th grades. Participants maintained greater accuracy in identifying targets in the left quadrants (top/bottom) when compared with the right quadrants (top/bottom), revealing a leftward bias in their responses. Effects of gender and age were evident on performance; females scored significantly higher than males, and 9th graders scored significantly higher than 7th and 8th graders. Thus, a substantial shift in brain maturation may take place from 8th to 9th grades or from the ages of 13.0 to 14.11. Discriminative characteristics of the task are analyzed by assigning greater value to targets located in the top left quadrant. The 9th graders, as compared to the younger students, and the girls, as compared to the boys, evidenced a reading-direction-related bias toward systematic preference for the upper-left to lower-right quadrants.


Genetic and pharmacologic blockade of central melanocortin signaling attenuates cardiac cachexia in rodent models of heart failure.
The central melanocortin system plays a key role in the regulation of food intake and energy homeostasis. We investigated whether genetic or pharmacologic blockade of central melanocortin signaling attenuates cardiac cachexia in mice and rats with heart failure. Permanent ligation of the left coronary artery (myocardial infarction (MI)) or sham operation was performed in wild-type (WT) or melanocortin-4 receptor (MC4R) knockout mice. Eight weeks after surgery, WT-Sham mice had significant increases in lean body mass (LBM; P<0.05) and fat mass (P<0.05), whereas WT-MI did not gain significant amounts of LBM or fat mass. Resting basal metabolic rate (BMR) was significantly lower in WT-Sham mice compared to WT-MI mice (P<0.001). In contrast, both MC4-Sham and MC4-MI mice gained significant amounts of LBM (P<0.05) and fat mass (P<0.05) over the study period. There was no significant difference in the BMR between MC4-Sham and MC4-MI mice. In the second experiment, rats received aortic bands or sham operations, and after recovery received i.c.v. injections of either artificial cerebrospinal fluid (aCSF) or the melanocortin antagonist agouti-related protein (AGRP) for 2 weeks. Banded rats receiving AGRP gained significant amount of LBM (P<0.05) and fat mass (P<0.05) over the treatment period, whereas banded rats receiving aCSF did not gain significant amounts of LBM or fat mass. These results demonstrated that genetic and pharmacologic blockade of melanocortin signaling attenuated the metabolic manifestations of cardiac cachexia in murine and rat models of heart failure.


Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1 and 1.8 A resolution.
The crystal structure of rat transthyretin (rTTR) complex with 3,5,3',5'-tetraiodothyroacetic acid (T4Ac) was determined at 1.8 A resolution with low temperature synchrotron data collected at CHESS. The structure was refined to R = 0.207 and Rfree = 0.24 with the use of 8-1.8 A data. The additional 8000 reflections from the incomplete 2.1-1.8 data shell, included in the refinement, reduced the Rfree index by 1.3%. Structure comparison with the model refined against the complete 8-2.1 A data revealed no differences in the ligand orientation and the conformation of the polypeptide chain in the core regions. However, the high-resolution data included in the refinement improved the model in the flexible regions poorly defined with the lower resolution data. Also additional sixteen water molecules were found in the difference map calculated with the extended data. The structure revealed both forward and reverse binding of tetraiodothyroacetic acid in one binding site and two modes of forward ligand binding in the second site, with the phenolic iodine atoms occupying different sets of the halogen binding pockets.


Clinical Case of Respiratory Eucoleosis in a Dog from Bosnia and Herzegovina.
This case report describes a clinical case of patent and natural infection with trichuroid Eucoleus aerophilus in a 5-month-old, mixed-breed female dog in Bosnia and Herzegovina. A detailed history was taken from the owner. Physical exam and thoracic radiography were performed. Faecal sample was processed by the passive flotation tube test with saturated zinc sulphate solution. After the final diagnosis, a dose of 0.4 mg /kg ivermectin was applied subcutaneously to the diseased dog. The history revealed intermittent, non-productive cough after physical exercise. During the physical exam, mild signs of general distress, moderate cachexia with bad body condition, increased heart and respiratory rates, mild dyspnoea and increased bronchovesicular respirations were observed. Thoracic radiography showed mixed bronchial-alveolar lung pattern compatible with chronic bronchopneumonia. Trichuroid eggs of Eucoleus aerophilus were detected in faecal samples from the affected dog. Ivermectin administration at a dose of 0.4 mg/kg was sufficient to eliminate parasitic infection with Eucoleus aerophilus. This is the first report of respiratory eucoleosis in a dog from Bosnia and Herzegovina.


Microfluidic fabrication of monodisperse biocompatible and biodegradable polymersomes with controlled permeability.
We describe a versatile technique for fabricating monodisperse polymersomes with biocompatible and biodegradable diblock copolymers for efficient encapsulation of actives. We use double emulsion as a template for the assembly of amphiphilic diblock copolymers into vesicle structures. These polymersomes can be used to encapsulate small hydrophilic solutes. When triggered by an osmotic shock, the polymersomes break and release the solutes, providing a simple and effective release mechanism. The technique can also be applied to diblock copolymers with different hydrophilic-to-hydrophobic block ratios, or mixtures of diblock copolymers and hydrophobic homopolymers. The ability to make polymer vesicles with copolymers of different block ratios and to incorporate different homopolymers into the polymersomes will allow the tuning of polymersome properties for specific technological applications.


Cardiac efficiency.
Efficiency is defined as the ratio of the energy delivered by a system to the energy supplied to it. Depending on the particular question being addressed, there exist a plethora of definitions of efficiency in medical texts, thus hampering their comparison. If only the ventricular work seen by the arterial system is under investigation, pressure-volume work will serve as a useful numerator. If, on the other hand, external and internal work together, i.e. the total mechanical work, is of interest, the pressure-volume area might be employed. Total myocardial oxygen consumption (MVO2) will be a useful denominator in the case of aerobic energy production. The MVO2 for the unloaded contraction must be assessed if, as in other energy transfer systems, net efficiency is to be addressed. If even smaller steps in the chain of energy transfer are to be investigated MVO2 for the arrested heart must be assessed. With an appropriate therapy, hemodynamic determinants can be varied, to improve cardiac efficiency. Nonetheless, measurement of all variables necessary for the calculation of efficiency remains a challenge, in particular in the clinical setting. Separation of the direct effects of drugs on efficiency is even more difficult, since hemodynamic conditions can hardly be controlled throughout the observation period, and changes in efficiency might be secondary to changes in hemodynamics. Whether the heart by itself employs mechanisms to improve its efficiency is still a matter of discussion: there is evidence that when oxygen supply decreases, the heart can switch from one substrate to a less costly one, or possibly can improve efficiency through better use of oxygen. Moreover, the heart seems to "sense" an even more decreased oxygen supply and reduce function in response. Myocardial stunning could be regarded as a protective mechanism as well, with function remaining depressed and the oxygen supply being normal or close to normal. One may conclude from the decreased efficiency that the excess oxygen consumption is used up for repair processes. The improved efficiency found in hypertrophied hearts represents another adaptive process. The underlying mechanism is unclear: a shift towards isomyosin V3 or some undefined shift in metabolic pathway is discussed. It is also still a moot question towards which objective the efficiency of the heart is adjusted. It has been described that under physiologic conditions, the efficiency of both the left and the right ventricle ought to be maximized.(ABSTRACT TRUNCATED AT 400 WORDS)


Graphene Nanoribbons with Atomically Sharp Edges Produced by AFM Induced Self-Folding.
The ability to create graphene nanoribbons with atomically sharp edges is important for various graphene applications because these edges significantly influence the overall electronic properties and support unique magnetic edge states. The discovery of graphene self-folding induced by traveling wave excitation through atomic force microscope scanning under a normal force of less than 15 nN is reported. Most remarkably, the crystallographic direction of self-folding may be either along a chosen direction defined by the scan line or along the zigzag or armchair direction in the presence of a pre-existing crack in the vicinity. The crystalline direction of the atomically sharp edge is confirmed via careful lateral force microscopy measurements. Multilayer nanoribbons with lateral dimensions of a few tens of nanometers are realized on the same graphene sheet with different folding types (e.g., z-type or double parallel). Molecular dynamics simulations reveal the folding dynamics and suggest a monotonic increase of the folded area with the applied normal force. This method may be extended to other 2D van der Waals materials and lead to nanostructures that exhibit novel edge properties without the chemical instability that typically hinders applications of etched or patterned graphene nanostructures.


A six nuclear gene phylogeny of Citrus (Rutaceae) taking into account hybridization and lineage sorting.
Genus Citrus (Rutaceae) comprises many important cultivated species that generally hybridize easily. Phylogenetic study of a group showing extensive hybridization is challenging. Since the genus Citrus has diverged recently (4-12 Ma), incomplete lineage sorting of ancestral polymorphisms is also likely to cause discrepancies among genes in phylogenetic inferences. Incongruence of gene trees is observed and it is essential to unravel the processes that cause inconsistencies in order to understand the phylogenetic relationships among the species. (1) We generated phylogenetic trees using haplotype sequences of six low copy nuclear genes. (2) Published simple sequence repeat data were re-analyzed to study population structure and the results were compared with the phylogenetic trees constructed using sequence data and coalescence simulations. (3) To distinguish between hybridization and incomplete lineage sorting, we developed and utilized a coalescence simulation approach. In other studies, species trees have been inferred despite the possibility of hybridization having occurred and used to generate null distributions of the effect of lineage sorting alone (by coalescent simulation). Since this is problematic, we instead generate these distributions directly from observed gene trees. Of the six trees generated, we used the most resolved three to detect hybrids. We found that 11 of 33 samples appear to be affected by historical hybridization. Analysis of the remaining three genes supported the conclusions from the hybrid detection test. We have identified or confirmed probable hybrid origins for several Citrus cultivars using three different approaches-gene phylogenies, population structure analysis and coalescence simulation. Hybridization and incomplete lineage sorting were identified primarily based on differences among gene phylogenies with reference to null expectations via coalescence simulations. We conclude that identifying hybridization as a frequent cause of incongruence among gene trees is critical to correctly infer the phylogeny among species of Citrus.


The Acute Effects of External Compression With Blood Flow Restriction on Maximal Strength and Strength-Endurance Performance of the Upper Limbs.
The main goal of the present study was to evaluate the acute effects external compression with blood flow restriction (BFR) at 100 and 150% of full arterial occlusion pressure (AOP) on maximal strength and strength-endurance performance during the bench press (BP) exercise. The study included 12 strength-trained male subjects (age = 23.2 ± 2.66 years; body mass = 75.3 ± 6.33 kg; height = 179.1 ± 3.82 cm), experienced in resistance training (5.7 ± 2.93 years). During the experimental sessions in a randomized crossover design, the subjects performed a 1 repetition maximum (1RM) test and three sets of the BP using 60% 1RM to failure with three different conditions: without BFR (NO-BFR); BFR with a pressure of 100% AOP (BFR100); and BFR with a pressure of 150% AOP (BFR150). The differences between the NO-BFR, BFR100, and BFR150 conditions were examined using repeated measures ANOVA. The ANOVA indicated significant main effect for condition in 1RM, number of performed repetitions (REP), and time under tension (TUT) (p < 0.01). Post hoc analyses for the main effect indicated significant increases in 1RM (p < 0.01; 95.00 ± 15.37 vs 91.87 ± 15.99), REP (p < 0.01; 17.56 ± 3.36 vs 15.67 ± 5.24), and TUT (p < 0.01; 32.89 ± 6.40 vs 28.72 ± 6.18) for the BFR150 condition compared to NO-BFR. Furthermore, significant increases in REP (p = 0.03; 17.56 ± 3.36 vs 16.47 ± 4.01) and TUT (p = 0.03; 32.89 ± 6.40 vs 30.00 ± 6.45) were observed for the BFR150 condition compared to the BFR100. The results of the present study indicate that high external compression increases maximal strength evaluated by the 1RM test, as well as endurance performance during three sets of the BP exercise.


Successful Procedure in Conservative Management of Interstitial (Cornual) Ectopic Pregnancy.
A 35-year-old woman presented with spotting and lower abdominal pain. Follow-up sonography was suggestive of interstitial ectopic pregnancy. Laparoscopic cornuostomy was carried out. Before incision, diluted vasopressin was injected around the site of interstitial pregnancy. Removal of the conceptual tissues was conducted smoothly through a 1.5 cm incision. The overall blood loss was 50 mL. The operative time was 50 min, and there were no intraoperative complications. We successfully performed laparoscopic cornuostomy, which was followed by an unremarkable postoperative course. Laparoscopic surgery is a safe and effective minimally invasive surgical intervention for interstitial ectopic pregnancy if performed by the experienced surgeon. Local vasopressin injection is a good alternative for bleeding control in conservative laparoscopic surgery.


Nodal Epstein-Barr virus-positive T-cell/NK-cell lymphoma associated with immunodeficiency: a rare condition looking for recognition.
The authors describe a peculiar form of Epstein-Barr virus (EBV)-associated T-cell lymphoma in an HIV-positive patient presenting an aggressive clinical course. Unlike most other EBV-positive T-cell/natural-killer (NK)-cell lymphomas, the disease was characterized by predominant nodal involvement at presentation. T-cell lineage was confirmed by T-cell receptor-rearrangement, and neoplastic cells exhibited strong and diffuse CD56 expression. A marked intravascular component was detected in the skin, the liver, and the lung parenchyma. This entity was not predicted in the WHO 2008 classification, but has been recently identified in immunocompromised patients. This case report refers to a middle-aged man with AIDS, who presented a 4-month history of weight loss, fever, hepatosplenomegaly, peripheral and deep-chain lymphadenopathy. A blood smear showed lymphocytosis with a marked presence of atypia. The outcome was unfavorable and the patient could not be treated. The autopsy revealed multivisceral involvement, including lymph nodes, spleen, bone marrow, liver, lungs, skin, and kidneys.


[Prostaglandin E1--the pharmacologic prosthesis].
The treatment of erectile failure has developed rapidly over the last decade with the introduction of intracavernosal self injection therapy, first with phenoxybenzamine, then with papaverine and paraverine-phentolamine. These drugs are now progressively replaced by prostaglandin E1 mainly because of its efficacy and fewer side effects. Prostaglandin E1 can induce a rigid erection even in case of severe arteriopathy and offers an excellent alternative to a prosthetic implant.