Flat-head positioning increases cerebral blood flow in anterior circulation acute ischemic stroke. A cluster randomized phase IIb trial.
Background Whether lying-flat improves blood flow in patients with acute ischemic stroke is unknown. Our aim was to investigate if lying-flat "changes" cerebral blood flow velocities assessed by transcranial Doppler in acute ischemic stroke patients. Methods In a multicenter cluster clinical trial, we randomly assigned patients within 12 h from onset of a neurological deficit due to cerebral ischemia of the anterior circulation to lying-flat or upright head positioning. The primary outcome was a change of 8 cm/s or more in mean cerebral blood flow velocities on transcranial Doppler to the middle cerebral artery at 1 and 24 h post-randomization, adjusted for imbalance in baseline variables. Secondary outcomes included serious adverse events and physical functioning at 90 days. Results Ninety-four of 304 patients screened were recruited. The primary outcome occurred in 11 (26%) of 43 patients in the lying-flat group and in 6 (12%) of 51 in the upright group at 1 h (adjusted odds ratio, 3.81; 95% CI, 1.07 to 13.54), and in 23 (53%) and 18 (36%) patients in these respective groups at 24 h (adjusted odds ratio, 3.04; 95% CI, 1.08 to 8.53). There were no between-group differences in serious adverse events, including pneumonia, heart failure or mortality, nor in functional outcome at 3 months (adjusted common odds ratio, 1.38; 95% CI 0.64 to 3.00). Conclusion The lying-flat head position was associated with a significant increase in cerebral blood flow velocities at one and 24 h within the ipsilateral hemisphere of anterior circulation acute ischemic stroke, without serious safety concerns. Clinical trial registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT01706094.


Dual-polarization Dirac cones in a simple 2D square lattice photonic crystal.
We report on dual-polarization Dirac cones in a simple square lattice two-dimensional (2D) photonic crystal (PC) based on transmission at accidental degeneracies centered at the $k = {0}$k=0 symmetry ($ \Gamma $Γ) point. Finite difference time domain simulations are used to identify the material and geometric parameters for Dirac-like dispersion. A configuration that produces a Dirac-like point for both transverse electric and transverse magnetic polarizations at the same frequency is presented. The PC dispersion shows the expected threefold degenerate linear branch crossings at the Dirac-like point. Full-field electromagnetic wave simulations exhibit some common behaviors of devices based on Dirac-like dispersion, such as cloaking and waveguiding. The configuration works for a considerable range of the parameter space, and thus is experimentally realizable with a wide range of materials.


The medication advice-seeking network of staff in an Australian hospital renal ward.
Electronic medication systems may impact communication in hospital wards. To identify the ways in which communication patterns may be altered it is necessary to compare processes both before and after system introduction. This paper reports the use of a social network approach to examine the medication advice-seeking network of an Australian hospital renal ward before the introduction of an electronic medication management system. A social network questionnaire was completed by 96% of staff members (doctors, nurses, allied health professionals and administrative staff) on the ward (n=45). Survey data were analysed to produce a sociogram to display the medication advice-seeking network of the staff in the ward. The results showed that there was a relatively low level of advice-seeking about medication-related decisions and tasks. Most communication occurred within professional groups. Several key individuals were pivotal in providing advice both within and across professional groups.


Assistive technology: Understanding the needs and experiences of individuals with autism spectrum disorder and/or intellectual disability in Ireland and the UK.
Assistive technologies (ATs) aimed at improving the life quality of persons with Autism Spectrum Disorder and/or Intellectual Disability (ASD/ID) is an important research area. Few have examined how this population use and experience AT or their vision for future uses of AT. The present study aimed to update and extend previous research and provides insight from caregivers, and other stakeholders (n = 96), living in Ireland and the United Kingdom, on their experiences of assistive technology (AT) for ASD/ID. Caregiver and professional responses to an anonymous online survey showed that focus individuals were rated low in terms of independent and self-management skills, with scheduling and planning and communication identified as desirable future AT functions. Overall, positive experiences of AT were reported, with AT use more than doubling in recent years.


Cutting a fine figure: On the use of thin sections in electron microscopy to quantify autophagy.
Over the last few years, two guideline articles have been published with recommendations for assessing autophagy. These articles contained advice on quantification of autophagy by electron microscopy and proposed using thin slices for quantifying autophagic structures. Here, we expand on what can and cannot be quantified using single 2D slices and give some suggestions for efficient and minimally biased approaches for quantifying this fascinating and important process. We recommend that the journal Autophagy follow other journals in demanding stringent random sampling design and application of unbiased design-based quantification when reviewing submitted manuscripts.


Delusions of infestation treated by pimozide: a double-blind crossover clinical study.
Eleven patients with delusions of infestation were treated with pimozide using a double-blind crossover technique. Ten out of 11 patients improved. The investigation showed significant relief of itch and delusions during pimozide treatment. Brief Psychiatric Rating Scale (BPRS) points decreased significantly. Adverse effects were few by 2 patients showed dose-related depressive reactions during treatment. Pimozide treatment of patients with delusions of infestation should be entrusted to dermatologists, because these patients with delusions differ from most patients attending psychiatric clinics in that they have a monosymptomatic hypochondriacal psychosis.


LncRNA CCAT1 promotes the progression of preeclampsia by regulating CDK4.
Preeclampsia is one of the leading causes of maternal and perinatal deaths. This study mainly explored the mechanism of long non-coding RNA (lncRNA) CCAT1 expression in the placenta of preeclampsia patients and its effect on the progression of preeclampsia. We used quantitative reverse transcription PCR (qRT‑PCR) to detect the lncRNA CCAT1 expression in 40 preeclampsia and 40 normal pregnancy placenta samples. CCAT1 expression and its relationship with the clinicopathological parameters of preeclampsia was statistically analyzed. The specific small interfering RNA (si-CCAT1) and plasmid (pcDNA-CCAT1) targeting lncRNA CCAT1 were synthesized and transfected into Bew and JEG-3 cells. The CCAT1 expression in Bew and JEG-3 cells was determined by qRT‑PCR. The effect of overexpression and interference of lncRNA CCAT1 on the proliferation of Bew and JEG-3 cells was observed. The effect of CCAT1 on cell cycle was examined by cell cycle assay. The protein expression was accessed by Western blot. Higher lncRNA CCAT1 expression was found in preeclampsia patients. The systolic blood pressure, diastolic blood pressure and urine protein in preeclampsia patients were significantly higher than those in normal pregnant women. The birth weight of fetus was significantly lower than that of normal pregnant women. However, there was no significant difference in weight and age of patients. According to the CCAT1 expression, preeclampsia patients were assigned into high expression group and low expression group. Higher systolic blood pressure, diastolic blood pressure, and urinary protein levels in CCAT1 high expression group were observed comparing to those in low expression group, while the birth weight in low expression group was significantly higher than the high expression group. In addition, we found that after interference with CCAT1, trophoblast proliferation was significantly increased and cell cycle was significantly accelerated, whereas overexpression of CCAT1 led to the contrary. Western blotting indicated that the expressions of E2F1, cyclin D, CDK2 and CDK4 in BeWo cells were increased after CCAT1 was knocked down. The expressions of E2F1, cyclin D, CDK2 and CDK4 in JEG3 cells were decreased after CCAT1 was overexpressed. LncRNA CCAT1 was highly expressed in preeclampsia and can promote the progression of preeclampsia by inhibiting the expression of CDK4.


Suprascapular nerve block for the treatment of hemiplegic shoulder pain in patients with long-term chronic stroke: a pilot study.
Hemiplegic shoulder pain is the most common pain condition after stroke. Suprascapular nerve block is an effective treatment for shoulder pain. The aim of this pilot study was to evaluate the effects of suprascapular nerve block on pain intensity, spasticity, shoulder passive range of motion, and quality of life in long-term chronic stroke patients with hemiplegic shoulder pain. Ten chronic stroke patients (over 2 years from onset) with hemiplegic shoulder pain graded ≥30 mm on the Visual Analogue Scale underwent suprascapular nerve block injection with 1 mL of 40 mg/mL methylprednisolone and 10 mL 0.5% bupivacaine hydrochloride. Main outcome was the Visual Analogue Scale evaluated before and after nerve block at 1 h, 1 week, and 1 month. Secondary outcomes were the modified Ashworth scale and the shoulder elevation, abduction, and external rotation passive range of motion evaluated before the nerve block and after 1 h as well as the American Chronic Pain Association Quality of Life Scale evaluated before and after nerve block at 1 month. The Visual Analogue Scale significantly improved after nerve block at 1 h (P = 0.005) and 1 week (P = 0.011). Significant improvements were found at 1 h after nerve block in the modified Ashworth scale (P = 0.014) and the passive range of motion of shoulder abduction (P = 0.026), flexion (P = 0.007), and external rotation (P = 0.017). The American Chronic Pain Association Quality of Life Scale significantly improved at 1 month after nerve block (P = 0.046). Our findings support the use of suprascapular nerve block for treating hemiplegic shoulder pain in long-term chronic stroke patients.


3.0 T relaxation time measurements of human lymph nodes in adults with and without lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging.
The purpose of this work was to quantify 3.0 T (i) T1 and T2 relaxation times of in vivo human lymph nodes (LNs) and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment-related lymphedema (BCRL). MR relaxometry was performed over bilateral axillary regions at 3.0 T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T1 maps were calculated using a multi-flip-angle (20, 40, 60°) method with B1 correction (dual-TR method, TR1 /TR2 = 30/130 ms), and T2 maps using a multi-echo (TE = 9-189 ms; 12 ms intervals) method. T1 and T2 were quantified in the LN cortex and hilum. A Mann-Whitney U-test was applied to compare LN relaxometry values between patients and controls (significance, two sided, p < 0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean ± standard deviation) in healthy controls were T1 cortex, 1435 ± 391 ms; T1 hilum, 714 ± 123 ms; T2 cortex, 102 ± 12 ms, and T2 hilum, 119 ± 21 ms. T1 of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p < 0.001) and compared with bilateral control values (p < 0.01). The LN cortex T1 asymmetry discriminated cases from controls (p = 0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0 T T1 and T2 relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.


Concanavalin A, but not glycated albumin, increases subendothelial deposition of von Willebrand factor in vitro.
Diabetes is associated with augmentation of prothrombogenic von Willebrand factor (vWF) content in plasma. Earlier, the author and colleagues have shown that high glucose and insulin do not appreciably influence deposition of vWF into the subendothelial extracellular matrix (SECM) produced by cultured human umbilical vein endothelial cells (HUVECs). In the present work, the author used this model to test the effects of nonenzymatically glycated albumin (Glyc-HSA) and two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on vWF deposition into the SECM. First-passage HUVECs were seeded into gelatin-coated 96-well plates and cultured for 6 to 7 days. HSA or Glyc-HSA (at concentrations 25, 50, and 100 microg/mL), and WGA or ConA (4, 8, and 16 microg/mL) were added 3 h after seeding. Cell viability was tested by the MTT method. To determine vWF contents in the SECM, HUVECs were detached by treatment with NH4OH and the residual material was used as a solid phase in an enzyme-linked immunosorbent assay (ELISA)-like assay with primary (anti-vWF) and secondary (peroxidase-conjugated) antibodies. Addition of Glyc-HSA did not essentially influence VWF contents in the SECM (A490 was 0.226 versus 0.268 at 0 and 100 microg/mL, respectively; p > .05, n = 16). Cultivation in the presence of WGA led to the deterioration of cell viability, which was accompanied by a significant decrease of vWF in the SECM (0.248 versus 0.128 at 0 and 16 microg/mL, respectively; p < .001, n = 16). ConA did not influence viability of HUVECs, but this lectin at all concentrations consistently increased the deposition of vWF (up to 164% relative to control, p <.001; n = 16). These data indicate that endothelial carbohydrate determinants and corresponding ligands (namely, mannose-specific lectins) may be involved in the regulation of production and deposition of vWF.


A New Ensemble Classification System For Fracture Zone Prediction Using Imbalanced Micro-CT Bone Morphometrical Data.
Trabecular bone fractures constitute a major health issue for the modern societies, with the currently established prediction methods of fracture risk, such as bone mineral density (BMD), resulting in errors up to 40%. Fracture-zone prediction based on bone's microstructure has been recently proposed as an alternative prediction method of fracture risk. In this paper, a classification system (CS) for the automatic fracture-zone prediction based on an Ensemble of Imbalanced Learning methods is proposed, following the observation that the percentage of the actual fractured bone area is significantly smaller than the intact bone in the case of a fracture event. The sample is divided into Volumes of Interest (VOIs) of specific size and 29 morphometrical parameters are calculated from each VOI, which serve as input features for the CS in order for it to separate the input patterns in to two classes: fractured and nonfractured. To this end, two well-established Imbalanced Learning methods, namely Random Undersampling and Synthetic Minority Oversampling, and two popular classification algorithms, namely Multilayer Perceptrons and Support Vector Machines, are tested and combined accordingly, to provide the best possible performance on a dataset that contains 45 specimens' pre- and postfailure scans. The best combination is then compared with three well-established Ensembles of Imbalanced Learning methods, namely RUSBoost, UnderBagging and SMOTEBagging. The experimental results clearly show that the proposed CS outperforms the competition, scoring in some occasions more than 90% in G-Mean and Area under Curve metrics. Finally, an investigation on the significance of the various trabecular bone's biomechanical parameters is made using the sequential forward floating selection technique, in order to identify possible biomarkers for fracture-zone prediction.


Scanning electron microscopical observation of the intramitochondrial body in the bovine corpus luteum during pregnancy and after parturition.
Large luteal cells of the bovine pregnant luteum can be characterized as steroid-producing cells. Mitochondria of these cells contained intramitochondrial bodies (IMB). The three-dimensional structure of the IMB and the degenerative process of luteal cells were as follows: 1) The IMBs were globular or oval, 0.1 to 1.5 microns in diameter. Their outer surfaces were coarse but their cut surfaces were uniform. Their outer surfaces changed from rough to smooth during pregnancy. 2) At the late stage of pregnancy, the large luteal cells lost their cytoplasmic processes, showing the first sign of degeneration at the cell level in such a way that their mitochondrial cristae transformed from tubular to laminar, and that they contained accumulated lipid droplets. 3) After parturition, the IMBs came out from degenerating large luteal cells, and were conveyed by lymphatic capillaries.


Comparisons of Two Bioelectrical Impedance Devices and Manual versus Sensor-Based Short Physical Performance Batteries for Assessment of Muscle Mass and Physical Performance.
The assessment of muscle mass and physical performance is essential for the diagnosis of sarcopenia. This study examined the validity of bioimpedance analysis (BIA) and a sensor-based short physical performance battery (SPPB) device for analyzing appendicular skeletal muscle mass (ASM) and physical performance. Forty-one older adults were measured for ASM and physical performance with two BIA devices (InBody770 vs. T-SCAN PLUS III) and two SPPB devices (manual mSPPB vs. sensor-based sSPPB). Validity statistics included the intraclass correlation coefficient (ICC) and Bland-Altman plots to examine the agreement of data from the BIA (InBody770 vs. T-SCAN PLUS III) and the SPPBs (mSPPB vs. sSPPB). There was a significant ICC for skeletal muscle mass between the T-SCAN PLUS III and InBody770 devices (ICC = 0.8822; p < 0.0001). The mSPPB and sSPPB values showed agreement across all components: 0.8654 for the total scores, 0.8879 for the walking speed, 0.8889 for the chair stand, and 0.6863 for the standing balance. No systemic bias was observed between the two methods for the BIA and SPPB devices. Measurements using the T-SCAN PLUS III and sSPPB seem to be highly correlated with the InBody770 and mSPPB devices in older adults and may be valid for assessing muscle mass and physical performance.


Size-Dependent Catalytic Activity of Palladium Nanoparticles Fabricated in Porous Organic Polymers for Alkene Hydrogenation at Room Temperature.
Ultrafine palladium nanoparticles (Pd NPs) with 8 and 3 nm sizes were effectively fabricated in triazine functionalized porous organic polymer (POP) TRIA that was developed by nonaqueous polymerization of 2,4,6-triallyoxy-1,3,5-triazine. The Pd NPs encapsulated POP (Pd-POP) was fully characterized using several techniques. Further studies revealed an excellent capability of Pd-POP for catalytic transfer hydrogenation of alkenes at room temperature with superior catalytic performance and high selectivity of desired products. Highly flammable H2 gas balloon at high pressure and temperature used in conventional hydrogenation reactions was not needed in the present synthetic system. Catalytic activity is strongly dependent on the size of encapsulated Pd NPs in the POP. The Pd-POP catalyst with Pd NPs of 8 nm in diameter exhibited higher catalytic activity for alkene hydrogenation as compared with the Pd-POP catalyst encapsulating 3 nm Pd NPs. Computational studies were undertaken to gain insights into different catalytic activities of these two Pd-POP catalysts. High reusability and stability as well as no Pd leaching of these Pd-POP catalysts make them highly applicable for hydrogenation reactions at room temperature.


Subcellular localization of angiotensin-converting enzyme in the human alveolar macrophage.
The present investigation was performed in order to elucidate the subcellular localization of angiotensin-converting enzyme (ACE) in human alveolar macrophages. A pure population of alveolar macrophages was obtained by centrifugal elutriation of bronchoalveolar lavage (BAL) fluid from seven sarcoid patients. The cells were homogenized by sonication and the postnuclear supernatant was fractionated on a discontinuous sucrose gradient. Fractions of particulate material were collected and characterized by marker enzymes. The distribution pattern of ACE closely resembled that of NADPH-cytochrome-c-reductase and sialyltransferase, markers of the endoplasmic reticulum and the Golgi complex, respectively, indicating a common localization. This localization is compatible with synthesis taking place in the alveolar macrophage.


Phenotypic changes induced by IL-12 priming regulate effector and memory CD8 T cell differentiation.
In addition to TCR and co-stimulatory signals, inflammatory cytokines such as IL-12 provide important signals for differentiation and survival of activated CD8 T cells. In the present study, to investigate the mechanisms by which IL-12 priming contributes to activation and enhanced survival of CD8 T cells, we searched the differentially regulated genes and markers by IL-12 during antigenic stimulation. Here, we show that IL-12 priming results in the increased subpopulation of CD127(hi) cells, which differentiates into long-lived memory cells. We also found that IL-12 priming induces IL-10 expression from activated CD8 T cells, which is distinct from CD127 up-regulation. Direct IL-10 priming of CD8 T cells results in the significant increase of effector and memory CD8 T cell population after adoptive transfer, and this priming effect is closely associated with less susceptibility to apoptosis. Although IL-10 is known as a cytokine with anti-inflammatory and immunosuppressive properties, our results have shown that IL-10 has a direct and positive effect on the survival of CD8 T cells. Together, we suggest that IL-10-dependent and independent effects of IL-12 play important roles in regulating differentiation and survival of activated CD8 T cells into effector and memory cells.


A modular design of low-background bioassays based on a high-affinity molecular pair barstar:barnase.
High-affinity molecular pairs provide a convenient and flexible modular base for the design of molecular probes and protein/antigen assays. Specificity and sensitivity performance indicators of a bioassay critically depend on the dissociation constant (K(D)) of the molecular pair, with avidin:biotin being the state-of-the-art molecular pair (K(D) ∼ 1 fM) used almost universally for applications in the fields of nanotechnology and proteomics. In this paper, we present an alternative high-affinity protein pair, barstar:barnase (K(D) ∼ 10 fM), which addresses several shortfalls of the avidin:biotin system, including non-negligible background due to the non-specific binding. A quantitative assessment of the non-specific binding carried out using a model assay revealed inherent irreproducibility of the [strept]avidin:biotin-based assays, attributed to the avidin binding to solid phases, endogenous biotin molecules and serum proteins. On the other hand, the model assays assembled via a barstar:barnase protein linker proved to be immune to such non-specific binding, showing good prospects for high-sensitivity rare biomolecular event nanoproteomic assays.


Myofascial pain: the great mimicker and potentiator of other diseases in the performing artist.
The performing artist often sustains a variety of neuromusculoskeletal problems that interfere with the ability to play or perform. Although many of these conditions occur as a result of overuse or misuse; other causes should be kept in mind--particularly when pain problems persist, recur, or do not respond to usual therapeutic measures. Chief among these are myofascial pain syndromes. These are quite common but are often overlooked, despite the fact that they can cause, potentiate the dysfunction of, and mimic other conditions. This article presents an overview of myofascial pain and dysfunction--particularly as it pertains to neuromusculoskeletal pain and disability in musicians and performing artists.


APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration.
The safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial. This phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy. Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet. At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy. 157 patients were enrolled. Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis. The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001). There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively. X-82 oral therapy in combination with pro re nata anti-VEGF injections showed non-inferiority in visual acuity outcomes while achieving a dose-dependent decrease in the number of anti-VEGF injections compared with placebo. Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.


P2X receptor-dependent erythrocyte damage by α-hemolysin from Escherichia coli triggers phagocytosis by THP-1 cells.
The pore-forming exotoxin α-hemolysin from E. coli causes a significant volume reduction of human erythrocytes that precedes the ultimate swelling and lysis. This shrinkage results from activation of Ca2+-sensitive K+ (KCa3.1) and Cl- channels (TMEM16A) and reduced functions of either of these channels potentiate the HlyA-induced hemolysis. This means that Ca2+-dependent activation of KCa3.1 and TMEM16A protects the cells against early hemolysis. Simultaneous to the HlyA-induced shrinkage, the erythrocytes show increased exposure of phosphatidylserine (PS) in the outer plasma membrane leaflet, which is known to be a keen trigger for phagocytosis. We hypothesize that exposure to HlyA elicits removal of the damaged erythrocytes by phagocytic cells. Cultured THP-1 cells as a model for erythrocytal phagocytosis was verified by a variety of methods, including live cell imaging. We consistently found the HlyA to very potently trigger phagocytosis of erythrocytes by THP-1 cells. The HlyA-induced phagocytosis was prevented by inhibition of KCa3.1, which is known to reduce PS-exposure in human erythrocytes subjected to both ionomycin and HlyA. Moreover, we show that P2X receptor inhibition, which prevents the cell damages caused by HlyA, also reduced that HlyA-induced PS-exposure and phagocytosis. Based on these results, we propose that erythrocytes, damaged by HlyA-insertion, are effectively cleared from the blood stream. This mechanism will potentially reduce the risk of intravascular hemolysis.


Albuminuria and Glomerular Filtration Rate in Individuals with Type 1 Diabetes Mellitus: Contribution of Metabolic Syndrome.
The development of metabolic syndrome has been described in patients with type 1 diabetes mellitus as the disease progresses over time. The purpose of this study is to assess the relationship between metabolic syndrome, albuminuria, and glomerular filtration rate, as well as to determine the prevalence of metabolic syndrome, in a group of Mexican patients with type 1 diabetes mellitus. We conducted a cross-sectional study that included patients with type 1 diabetes mellitus who were diagnosed over 10 years ago and who are seen at the Diabetes Intensive Control Clinic of the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran in Mexico City. The presence of metabolic syndrome was determined by using the National Cholesterol Education Program-Adult Treatment Panel III (ATP III) criteria. A total of 81 individuals were studied. The prevalence of metabolic syndrome was 18.5% (n = 15). A higher albuminuria was found in subjects with metabolic syndrome (34.9 mg/24 hours; 8.3-169.3) than in those without metabolic syndrome (9.0 mg/24 hours; 5.0-27.0; p = 0.02). Glomerular filtration rate was lower in patients with metabolic syndrome (95.3 ml/minute; [64.9-107.2] vs. 110.2 ml/minute [88.1-120.3]; p = 0.04). After classifying the population according to the number of metabolic syndrome criteria, a progressive increase in albuminuria and a progressive decrease in glomerular filtration rate were found with each additional metabolic syndrome criterion (p = 0.008 and p = 0.032, respectively). After adjusting for age, time from diagnosis, systolic blood pressure, triglycerides, HDL-cholesterol, and treatment with angiotensin receptor blockers or angiotensin converting enzyme inhibitors, we found that age, time from diagnosis, triglycerides, and HDL-cholesterol were independent factors associated with glomerular filtration rate (R2 = 0.286; p < 0.001). Metabolic syndrome was associated with a higher albuminuria and a reduction in glomerular filtration rate in patients with type 1 diabetes mellitus. Metabolic syndrome was present in 18.5% of this group of Mexican individuals with type 1 diabetes mellitus.


Burnout among urologists linked to status and hierarchy.
This article includes partial excerpts from Dr. Robert Pearl's upcoming book, "Uncaring: How The Culture Of Medicine Kills Doctors And Patients." This book contains specific and detailed solutions for reforming both the system and culture of healthcare. See online sellers for preorder information. All profits from the book will be donated to Doctors Without Borders.


[CMV infections].
Infections with cytomegalovirus are widespread among populations. The frequency of anti-CMV bodies occurrence in healthy adults is from 40% in Europe to 100% in the Third World countries. The research carried out in Poland on two thousand healthy women at productive age showed in more than half of them the presence of anti-CMV bodies before pregnancy. It is especially significant in the context of the possibility of primary CMV infection in gravidas and the transmission into the fetus. Confirmation of the primary CMV infection in women at an early stage of pregnancy requires further prenatal diagnosis. CMV is asymptomatic in 99% of cases. It is especially dangerous for neonates, in whom heavy cytomegalovirus disease is connected with immaturity of the immunological system, and for people with immunological system disorders (after transplantations or HIV infections). Clinical forms of CMV infections have been presented here, with some of them being illustrated with descriptions of cases observed at the Clinic; methods of CMV infection treatment in various groups of patients, as well as the state of knowledge about anti-CMV vaccine are also presented.


Assessment of Noise Levels of Equipment Used in the Practical Dental Teaching Activities.
Practical activities in dentistry are characterized by a high noise level that can have adverse effects on the hearing health of professors, students, and teaching staff. The objective of our study was to make an assessment of the noise level during the practical fixed prosthodontics activities in the Faculty of Dentistry of Casablanca. We conducted a descriptive cross-sectional study to measure the noise level in the practical room of fixed prosthodontics. The measurements were obtained during 4 sessions over a duration of 2 hours and 30 minutes, each with the use of a SdB + sound level meter at 4 different locations. The results showed the following: an average value of 69.35 dB (A) for the first practical session (south), an average value of 71.07 dB (A) for the 2nd practical session (east), an average value of 70.36 dB (A) for the 3rd practical session (west), and an average value of 72.06 dB (A) for the 4th practical session (center of the room). Discussion and Conclusion. The results obtained are similar to the results found in previous studies in other countries. These results are below the thresholds of the legislation and international standards. However, we have recorded punctual peaks that exceed the recommended level, requiring the introduction of the means of prevention and the measures of safety against the noise as well at the level of the practical activity classroom and the realization of more in-depth studies concerning the evaluation of the daily exposure of the professors, students, and teaching staff to noise.


Primary, secondary and tertiary effects of eco-climatic change: the medical response.
Climatic and ecological change threaten human health globally. Manifestations include lost species, vanishing glaciers and more frequent heavy rain. In the second half of this century, accelerating sea level rise is likely to cause crop loss, and population dislocation. These problems may be magnified by dysfunctional human responses, including conflict. The population health consequences of these events can be classified as primary, secondary and tertiary. Primary signs include the acute and chronic stress of heat waves, and trauma from increased bush fires and flooding. Secondary signs are indirect, such as an altered distribution of arthropod vectors, intermediate hosts and pathogens that will produce changes in the epidemiology of many infectious diseases. More severe future health consequences of climate change are classified here as tertiary effects. If moderate or severe climate change scenarios prove accurate then these manifestations will occur over large areas, and could include famine, war and significant population displacement. Such effects would threaten governance and health. The health professions must respond to these challenges, especially the task of recognising and seeking to minimise tertiary health consequences. The gap between what we know and what we need to know concerning these issues can be narrowed by a new field of medical practice. The framework for this emerging discipline includes climate change, ecology and global health. Combined, these dimensions may be called ecomedicine. Actions to reduce individual emissions, to promote active transport (with its 'co-benefit' of preventing chronic disease), and involvement in group action to protect the environment and to prevent war, informed by understanding of the health of individual patients and populations, will be central to the practice of ecomedicine.


Long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses in children: An ultrasound biomicroscopy study.
To evaluate the long-term outcomes of ciliary sulcus versus capsular bag fixation of intraocular lenses (IOLs) in children after pediatric cataract surgery. IOL was implanted in the ciliary sulcus in 21 eyes of 14 children, and in the capsular bag in 19 eyes of 12 children for the treatment of pediatric cataract in an institutional setting. Ultrasound biomicroscopy (UBM) was performed. Main outcome measures included IOL decentration, IOL tilt, anterior chamber depth (ACD), angle-opening distance at 500 μm (AOD500), trabecular-iris angle (TIA), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and incidence of postoperative complications. The mean follow-up period was 6.81 ± 1.82 years. Comparing to the capsular bag fixation group, the ciliary sulcus fixation group had higher vertical IOL decentration, horizontal IOL tilt, and vertical IOL tilt (p = 0.02, 0.01,0.01, respectively), higher incidence of iris-IOL contact and peripheral anterior synechia (p = 0.001, 0.03, respectively), smaller ACD, AOD500, and TIA (p = 0.02, 0.03, 0.04, respectively), higher mean IOP (17.10 ±6.06 mmHg vs.14.15± 4.74 mmHg, p = 0.01), and higher incidence of secondary glaucoma (28.57% vs. 10.53%, p = 0.007).There was no significant difference between the two groups with regard to the BCVA, refractive errors, incidence of myopic shift, nystagmus, strabismus, and visual axis opacity. Ciliary sulcus fixation of IOLs in pediatric eyes may increase IOL malposition and crowding of the anterior segment, and may associate with a higher risk of secondary glaucoma compared to capsular bag fixation of IOLs.


[Treatment of portal hypertension by portosystemic shunts].
The use of shunts for the treatment of portal hypertension has been revived after the introduction of the transjugular intrahepatic portosystemic shunt (TIPS) into clinical practice. This interventional procedure has mainly been used as rescue treatment for variceal bleeding resistant to endoscopic therapy and for ascites refractory to diuretic treatment and paracentesis. With respect to variceal bleeding TIPS has a low rate of "operative" mortality of < 1% and variceal rebleeding of 6 to 18%. In patients with refractory ascites the response to treatment is 50 to 92%. The major problems of the TIPS procedure are the increased incidence of hepatic encephalopathy and the high rate of shunt insufficiency of about 50%. Therefore, control of shunt function by duplex-sonography is essential to detect malfunction of the shunt. Radiological revision is then indicated if the clinical symptoms of portal hypertension (varices, ascites) reappear. The TIPS treatment has partially replaced the surgical shunting procedures. This decision is based on the potentially higher mortality of the surgical procedure. However, this has not been proven by randomized studies and, therefore, surgical shunts may also be indicated in selected patients with low operative mortality.


A case of severe vestibular root angulation.
In this article, we describe the appearance and management of an impacted permanent tooth with severe vestibular root angulation. In addition, the possible origin of this type of root malformation as well as some of their epidemiologic aspects are discussed.


Inference of functional divergence among proteins when the evolutionary process is non-stationary.
Functional shifts during protein evolution are expected to yield shifts in substitution rate, and statistical methods can test for this at both codon and amino acid levels. Although methods based on models of sequence evolution serve as powerful tools for studying evolutionary processes, violating underlying assumptions can lead to false biological conclusions. It is not unusual for functional shifts to be accompanied by changes in other aspects of the evolutionary process, such as codon or amino acid frequencies. However, models used to test for functional divergence assume these frequencies remain constant over time. We employed simulation to investigate the impact of non-stationary evolution on functional divergence inference. We investigated three likelihood ratio tests based on codon models and found varying degrees of sensitivity. Joint effects of shifts in frequencies and selection pressures can be large, leading to false signals for positive selection. Amino acid-based tests (FunDi and Bivar) were also compromised when several aspects of the substitution process were not adequately modeled. We applied the same tests to a core genome "scan" for functional divergence between light-adapted ecotypes of the cyanobacteria Prochlorococcus, and carried out gene-specific simulations for ten genes. Results of those simulations illustrated how the inference of functional divergence at the genomic level can be seriously impacted by model misspecification. Although computationally costly, simulations motivated by data in hand are warranted when several aspects of the substitution process are either misspecified or not included in the models upon which the statistical tests were built.


IL-7 uniquely maintains FoxP3(+) adaptive Treg cells that reverse diabetes in NOD mice via integrin-β7-dependent localization.
Type 1 diabetes (T1D) develops as a consequence of a progressive autoimmune response that destroys insulin-producing β-cells in pancreatic islets. Because of their role(s) in controlling immune responses, considerable effort has been directed toward resolving whether regulatory T cells (Tregs) offer a clinical treatment to restore tolerance in T1D. We previously reported that in vitro-induced adaptive Treg cells (aTregs) can reverse T1D and persist as protective memory cells in the NOD mouse model. In the current study, we investigated mechanisms that regulate aTregs. We found that these FoxP3(+) aTregs expressed high levels of the IL-7 receptor, IL-7Rα, without the high affinity receptor for IL-2, CD25, which is found on natural Treg cells (nTregs). IL-7Rα expression was mirrored by the dependency of aTregs on IL-7 for persistence. IL-10 and TGF-β, effector cytokines of aTregs, were not essential for their maintenance at the level of systemic antibody blocking. Nevertheless, IL-10 modulated cytokine production by aTregs and TGF-β was critical for protection. aTregs were found to infiltrate islets and the expression of integrin-β7 was required for their localization in the pancreas. Furthermore, blocking aTreg entry into the pancreas prevented their control of diabetogenic effector T cells, implying the need for local control of the autoimmune response. The distinct homeostatic regulation of aTregs independently of a response to IL-2, which is defective in T1D patients, suggests that these cells represent a translatable candidate to control the autoimmune response.


Negligible fronto-parietal BOLD activity accompanying unreportable switches in bistable perception.
The human brain's executive systems have a vital role in deciding and selecting among actions. Selection among alternatives also occurs in the perceptual domain; for instance, when perception switches between interpretations during perceptual bistability. Whether executive systems also underlie this functionality remains debated, with known fronto-parietal concomitants of perceptual switches being variously interpreted as reflecting the switches' cause or as reflecting their consequences. We developed a procedure in which the two eyes receive different inputs and perception demonstrably switches between these inputs, yet the switches themselves are so inconspicuous as to become unreportable, minimizing their executive consequences. Fronto-parietal fMRI BOLD responses that accompanied perceptual switches were similarly minimized in this procedure, indicating that these reflect the switches' consequences rather than their cause. We conclude that perceptual switches do not always rely on executive brain areas and that processes responsible for selection among alternatives may operate outside the brain's executive systems.


What's unique about acute pancreatitis in children: risk factors, diagnosis and management.
Pancreatitis in children is an appreciable problem that has become increasingly prevalent. This Review covers the principles related to the definitions, epidemiology, risk factors, diagnosis and management of acute pancreatitis in children and identifies features that are unique among children. Additionally, knowledge gaps related to management principles are identified.


A virtual educational strategy on telemedicine and medical simulation.
Medical services in Columbia are scarce in many regions, not only because of accessibility problems and costs, but also because of difficulties in access to medical knowledge. We envision a long-term strategy for virtual education programs, based upon communication technologies that could be developed by private and government institutions. The diffusion of telemedicine concepts, applications, and technologies are critical for propagating medical knowledge. This paper describes the virtual education experiences at the Pontificia Universidad Javeriana.


[Enhancement of growth promoting activity of human blood on keratinocytes after its irradiation in vivo (transcutaneously) and in vitro with visible and infrared polarized light].
To stimulate wound healing, current medicine uses various methods of phototherapy. The induced activation of proliferative processes in the wound occurs due to development of not only local, but also systemic processes, whose nature remains largely uninvestigated. The present work provides evidences that as early as 30 min after irradiation of a small area of the volunteer's body surface with polychromatic visible light + infrared polarized light (400-3400 nm, 95% of polarization) at a therapeutic dose (12 J/cm2), soluble factors appear in the circulating blood, which are able to stimulate proliferation of human keratinocytes in primary culture. A similar effect was also revealed after a direct blood irradiation. A proof is provided in favor of a hypothesis that a rapid rise of growth promoting activity of the entire circulating blood may be a consequence of transcutaneous photomodification of the small amount of light-modified blood in superficial skin vessels, and of the effect of such blood on its entire circulating volume. A possibility of a release into plasma of growth factors from blood cells and complexes with alpha 2-macroglobulin is discussed.


Enhancing the tissue donor pool through donation after death in the field.
Tissue transplantation is an important adjunct to modern medical care and is used daily to save or improve patient lives. Tissue allografts include bone, tendon, corneas, heart valves and others. Increasing utilization may lead to tissue shortages, and tissue procurement organizations continue to explore ways to expand the cadaveric donor pool. Currently more than half of all deaths occur outside the acute care setting. Many who suffer prehospital deaths might be eligible for non-organ tissue donation. A retrospective review of electronic prehospital medical records was conducted from May 1, 2008 through December 31, 2009. All prehospital deaths were included irrespective of cause. Once identified, additional medical history was obtained from prehospital, inpatient, and emergency department records. Age, medical history, and time of death were compared to exclusion criteria for four tissue procurement organizations (MTF, LifeNet, LifeCell, EyeBank). After analysis, percentages of eligible donors were calculated. Over 50,000 prehospital records were reviewed; 432 subjects died in the field and were eligible for analysis. Ages ranged from four to 103 years of age; the average was 68.3 (SD = 20.1) years. After exclusion for age, medical conditions, and time of death, 185 unique patients (42.8%) were eligible for donation to at least one of the four tissue procurement organizations (range 11.6%-34.3%). After prehospital death, many individuals may be eligible for tissue donation. These findings suggest that future prospective studies exploring tissue donation after prehospital death are indicated. These studies should aim to clarify eligibility criteria, create protocols and infrastructure, and explore the ethical implications of expanding tissue donation to include this population.


Association between chromosomal aberration of exfoliated bladder cells in the urine and oxidative stress in patients with bladder transitional cell carcinoma.
The aim of the current study was to investigate the chromosomal aberrations of exfoliated bladder cells in the urine and blood oxidative stress in patients with bladder transitional cell carcinoma (BTCC). A total of 40 healthy controls and 246 patients with BTCC were recruited. Abnormal levels of CSP3, CSP7, CSP17 and GLPp16 were detected by fluorescence in situ hybridization (FISH) in exfoliated bladder cells in the urine of patients with BTCC. Serum total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured. Significant differences were observed in the abnormal CSP3, CSP7, CSP17, GLPp16 signals and FISH positive rate between patients with BTCC and healthy controls (P<0.001). Serum TOS, TAS and OSI were also significantly different between the two groups (P<0.001). The clinical stage of BTCC was not associated with abnormal CSP3, CSP7, CSP17, GLPp16 or FISH positive rate and oxidative stress (P>0.05). A Gamma rank correlation analysis revealed an association between the pathological grade of BTCC with abnormal CSP3, CSP7 and CSP17 as well as FISH positive rate (P<0.001). In addition, the clinical stage of BTCC was associated with serum TOS, TAS and OSI (P<0.001). Evaluation of the association between chromosomal aberrations and oxidative stress revealed that abnormal CSP3, CSP7 and CSP17 were positively associated with serum TOS and OSI (P<0.001), abnormal CSP7 and CSP17 were negatively associated with serum TAS (P<0.001), but abnormal GLPp16 was not associated with serum TOS, TAS or OSI (P>0.05). Therefore, the chromosomal aberrations of exfoliated bladder cells in the urine are associated with blood oxidative stress in patients with BTCC, and these factors may contribute to the occurrence and development of BTCC.


Intravitam diagnosis of human rabies by PCR using saliva and cerebrospinal fluid.
An optimized reverse transcription (RT)-PCR protocol for the intravitam detection of rabies virus genomic RNA was tested with clinical samples obtained from 28 patients suspected of having rabies, 9 of whom were confirmed to have had rabies by postmortem examination. RT-PCR using saliva combined with an immunofluorescence assay performed with skin biopsy samples allowed detection of rabies in the nine patients.


Absorption of ipsapirone along the human gastrointestinal tract.
Isapirone-HCl (5 mg) was administered orally, rectally and locally, by a remote control drug delivery device (HF-capsule) into different segments of the gastrointestinal tract, to four young healthy male adults. The relative systemic bioavailability of the drug from the colon and rectum was 2-3-fold greater than that from the upper gastrointestinal tract. This supports a rationale for a prolonged-release formulation.


Regulation of T cell production in T cell receptor transgenic mice.
The thymus produces many more cells than it releases into the periphery. According to generally accepted models of T cell development most of this loss occurs in the thymic cortex, among CD4+8+ thymocytes. An interesting situation arises in the case of T cell receptor (TcR) transgenic mice in which all cells can potentially be positively selected, leading to a theoretical increase of about 30-fold in the survival rate of CD4+8+ cells and in their transition to mature CD4+8- or CD4-8+ thymocytes. This in turn should lead to a 30-fold increase in the size of the thymic medulla, in the emigration rate and in the size of the peripheral T cell pool. Increases in medullary or peripheral pool sizes of this magnitude are not seen in TcR transgenic mice. The question was therefore asked whether some form of homeostatic process regulated the size of the mature T cell pool and at what level it might operate. In this report we demonstrate that the increased rate of double-positive to single-positive transition in the TcR transgenic mice is directly reflected in an increased emigration rate, and that the medulla seems to be relatively efficient regardless of the number of cells passing through it. However, the potential increases in emigrant numbers in TcR transgenic mice are offset by the reduced size of the CD4+8+ thymocyte pool. It would appear then that regulation of T cell production, if it occurs, probably does so through regulation of the size of the CD4+8+ thymocyte pool. Mechanisms for regulation of this kind are not yet known.


Professional regulation. Part 9: politics and ideology in nursing.
This article aims to continue the debate that surrounds nurse education and possible career structures. By reviewing two documents produced by the Department of Health and the Nursing and Midwifery Council, this article is concerned with one question: should nurses be free to decide their own career progression, or should they be compelled into the areas that the Government deem necessary to meet the demands of the populace? The answer this article produces is that no clear picture emerges. It becomes apparent that other, more powerful evidence may be in play, and that reference to other documents and political influences is needed; a review of this literature will be undertaken in the next article.


[The expressions of STAT3, WWOX and c-myc in human non small cell lung cancer tissue and correlativity analysis].
To investigate the expression of STAT3, WWOX and c-myc in non small cell lung cancer(NSCLC) and their clinical significance, and study their relation ship. Forty resected tissue samples from patients with NSCLC and twenty normal lung tissues were subjected to immunohistochemical staining(SP) for STAT3, WWOX and c-myc. (1)The positive expression rate of STAT3 and c-myc in NSCLC were 92.5% and 90% respectively, obviously higher than normal lung tissues (20% and 15%, P<0.01); The positive expression rate of WWOX was 30%, apparently lower than normal lung tissues(75%, P<0.01). (2) The expression levels of STAT3 and c-myc were related to pathologic types in NSCLC, which in adenocarcinomas were higher than squmous cell carcinomas (P<0.01), which were regardless with tumor size, histodifferentiation level, clinical stage and lymphatic metastasis; The expression of WWOX was ralated to whether lymph node metastasis in NSCLC(P<0.01).(3) There was a negativie correlation between the expressions of STAT3 and WWOX (r=-0.443, P<0.01); But no relationship was found between STAT3 and c-myc overexpression(r=-0.084) and between WWOX and c-myc overexpression(r=0.115). STAT3 and c-myc were overexpressed in human NSCLC. It indicated these proteins may make an important role in occurrence and development of lung cancer.The expressions of WWOX in human NSCLC was lower, which non expression was may related to the invision and metastasis of tumor. In the tumorigenesis of NSCLC, there is no relationship between expression of STAT3 and c-myc, They played independent roles in oncogenesis of NSCLC. There was a negativie correlation between the expressions of STAT3 and WWOX, but no relationship was found between WWOX and c-myc.


Strategies to improve the fluorescent signal of the tripartite sfGFP system.
Bimolecular fluorescence complementation (BiFC) is a popular method used to detect protein-protein interactions. For a BiFC assay, a fluorescent protein is usually split into two parts, and the fluorescence is recovered upon the interaction between the fused proteins of interest. As an elegant extension of BiFC, a tripartite superfold green fluorescent protein (sfGFP) system that has the advantages of low background fluorescence and small fusion tag size has been developed. However, the tripartite system exhibits a low fluorescence signal in some cases. To address this problem, we proposed to increase the affinity between the two parts, G1-9 and G11, of the tripartite system by adding affinity pairs. Among the three affinity pairs tested, LgBiT-HiBiT improved both the signal and signal-to-noise (S/N) ratio to the greatest extent. More strikingly, the direct covalent fusion of G11 to G1-9, which converted the tripartite system into a new bipartite system, enhanced the S/N ratio from 20 to 146, which is superior to the bipartite sfGFP system split at 157/158 or 173/174. Our results implied that the 10th β-strand of sfGFP has a low affinity and a good recovery efficiency to construct a robust BiFC system, and this concept might be applied to other fluorescent proteins with similar structure to construct new BiFC systems.


Making the most of federal health information technology regulations.
"Meaningful use" of interoperable electronic health records throughout the U.S. health care delivery system--the goal set forth in the American Reinvestment and Recovery Act (ARRA) of 2009--is a critical national goal. Proposed federal regulations on data exchange standards and the definition of meaningful use are well conceived and provide a foundation for the nation to begin the journey.


The French press: a repeatable and high-throughput approach to exercising zebrafish (Danio rerio).
Zebrafish are increasingly used as a vertebrate model organism for various traits including swimming performance, obesity and metabolism, necessitating high-throughput protocols to generate standardized phenotypic information. Here, we propose a novel and cost-effective method for exercising zebrafish, using a coffee plunger and magnetic stirrer. To demonstrate the use of this method, we conducted a pilot experiment to show that this simple system provides repeatable estimates of maximal swim performance (intra-class correlation [ICC] = 0.34-0.41) and observe that exercise training of zebrafish on this system significantly increases their maximum swimming speed. We propose this high-throughput and reproducible system as an alternative to traditional linear chamber systems for exercising zebrafish and similarly sized fishes.


Superinfection exclusion in duck hepatitis B virus infection is mediated by the large surface antigen.
Superinfection exclusion is the phenomenon whereby a virus prevents the subsequent infection of an already infected host cell. The Pekin duck hepatitis B virus (DHBV) model was used to investigate superinfection exclusion in hepadnavirus infections. Superinfection exclusion was shown to occur both in vivo and in vitro with a genetically marked DHBV, DHBV-ClaI, which was unable to establish an infection in either DHBV-infected ducklings or DHBV-infected primary duck hepatocytes (PDHs). In addition, exclusion occurred in vivo even when the second virus had a replicative advantage. Superinfection exclusion appears to be restricted to DHBV, as adenovirus, herpes simplex virus type 1, and vesicular stomatitis virus were all capable of efficiently infecting DHBV-infected PDHs. Exclusion was dependent on gene expression by the original infecting virus, since UV-irradiated DHBV was unable to mediate the exclusion of DHBV-ClaI. Using recombinant adenoviruses expressing DHBV proteins, we determined that the large surface antigen mediated exclusion. The large surface antigen is known to cause down-regulation of a DHBV receptor, carboxypeptidase D (CPD). Receptor down-regulation is a mechanism of superinfection exclusion seen in other viral infections, and so it was investigated as a possible mechanism of DHBV-mediated exclusion. However, a mutant large surface antigen which did not down-regulate CPD was still capable of inhibiting DHBV infection of PDHs. In addition, exclusion of DHBV-ClaI did not correlate with a decrease in CPD levels. Finally, virus binding assays and confocal microscopy analysis of infected PDHs indicated that the block in infection occurs after internalization of the second virus. We suggest that superinfection exclusion may result from the role of the L surface antigen as a regulator of intracellular trafficking.


Conformational transitions of a neurotensin receptor 1-Gi1 complex.
Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and the response to pain. Here we present structures of human NTSR1 in complex with the agonist JMV449 and the heterotrimeric Gi1 protein, at a resolution of 3 Å. We identify two conformations: a canonical-state complex that is similar to recently reported GPCR-Gi/o complexes (in which the nucleotide-binding pocket adopts more flexible conformations that may facilitate nucleotide exchange), and a non-canonical state in which the G protein is rotated by about 45 degrees relative to the receptor and exhibits a more rigid nucleotide-binding pocket. In the non-canonical state, NTSR1 exhibits features of both active and inactive conformations, which suggests that the structure may represent an intermediate form along the activation pathway of G proteins. This structural information, complemented by molecular dynamics simulations and functional studies, provides insights into the complex process of G-protein activation.


Alternaria alternata as endophyte and pathogen.
Alternaria alternata is a common species of fungus frequently isolated from plants as both an endophyte and a pathogen. Although the current definition of A. alternata rests on a foundation of morphological, genetic and genomic analyses, doubts persist regarding the scope of A. alternata within the genus due to the varied symbiotic interactions and wide host range observed in these fungi. These doubts may be due in large part to the history of unstable taxonomy in Alternaria, based on limited morphological characters for species delimitation and host specificity associated with toxins encoded by genes carried on conditionally dispensable chromosomes. This review explores the history of Alternaria taxonomy, focusing in particular on the use of nutritional mode and host associations in species delimitation, with the goal of evaluating A. alternata as it currently stands based on taxonomic best practice. Given the recombination detected among isolates of A. alternata, different symbiotic associations in this species should not be considered phylogenetically informative.


Consistency of heterogeneous synchronization patterns in complex weighted networks.
Synchronization within the dynamical nodes of a complex network is usually considered homogeneous through all the nodes. Here we show, in contrast, that subsets of interacting oscillators may synchronize in different ways within a single network. This diversity of synchronization patterns is promoted by increasing the heterogeneous distribution of coupling weights and/or asymmetries in small networks. We also analyze consistency, defined as the persistence of coexistent synchronization patterns regardless of the initial conditions. Our results show that complex weighted networks display richer consistency than regular networks, suggesting why certain functional network topologies are often constructed when experimental data are analyzed.


Clinical abnormalities, intervention program, and school attendance of Down syndrome children in southern Thailand.
Down syndrome is the most common chromosomal abnormality with an incidence of 1:700 livebirths. In southern Thailand, most Down syndrome patients are referred to Songklanagarind Hospital for surgical, medical treatment and/or stimulation intervention. To study the clinical features and school attendance of Down syndrome children. A total of 295 Down syndrome children attended Songklanagarind Hospital. The clinical features of Down syndrome, percentage of children receiving the stimulation intervention program, and attending school were studied. Congenital heart disease was found in 38.6%, gastrointestinal anomalies 16.9%, hematologic malignancy 6.1%, and thyroid disorders 11.4%. The mortality rate of Down syndrome children was 13.2%. Most children (65.6%) received the early stimulation, but only 38.9% attended the speech intervention program within the first 2 years of life. Of the total 109 Down syndrome children aged over 5 years that are still being followed, only 74 (67.9%) attended school. The school attendance was correlated with the family income, but not correlated with the level of maternal or paternal education. Congenital heart disease and gastrointestinal anomalies are commonly found in Down syndrome children. Most children received an early intervention program, but only 38.9% received speech intervention. In children aged >5 years, only 68% attended school, and school attendance was correlated with the family income.


Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.
The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.


Procedure for obtaining proper contour of an implant-supported crown: a clinical report.
Achieving proper contour of an implant-supported crown is essential for an esthetic result, particularly in the maxillary anterior area. Development of the soft tissue profile prior to the initiation of laboratory procedures is the ideal approach. This article describes a procedure that makes use of a soft tissue cast to permit crown fabrication prior to intraoral soft tissue customization.


Meta-analysis of Air Versus Liquid Enema for Intussusception Reduction in Children.
The purpose of this study was to assess the effectiveness and safety of air versus liquid enema reduction in the treatment of intussusception in children. Literature searches of the PubMed, Embase, and Cochrane Library databases were conducted from January 1, 1966, through May 31, 2013. Articles on the use of air or liquid enema in children with a confirmed diagnosis of intussusception and reporting either a success rate for enema reduction of intussusception or a perforation rate were selected. Enema reduction success rate, perforation rate, and recurrence rate were the main outcomes and were calculated by random effects modeling. One hundred two articles (101 reporting success rate, 71 reporting perforation rate) were included that presented results for 32,451 children (age range, 1 day-22 years; boys, 66%; girls, 34%). In 44 studies (16,187 children), the combined estimate for success rate of air enema was 82.7% (95% CI, 79.9-85.6%; inconsistency index [I(2)] = 97%), and in 52 studies (13,081 children) of liquid enema, it was 69.6% (95% CI, 65.0-74.1%; I(2) = 98%). In 38 studies (15,752 children), the combined estimate of perforation rate for air enema was 0.39% (95% CI, 0.23- 0.55%; I(2) = 40%), and in 30 studies (9429 children) of liquid enema, it was 0.43% (95% CI, 0.24- 0.62%; I(2) = 9%). Among 10,494 children (26 studies) undergoing air enema reduction, the rate of first intussusception recurrence was 6% (95% CI, 4.5-7.5%; I(2) = 89%), similar to the 7.3% (95% CI, 5.8-8.8%; I(2) = 71%) found for 4004 children (24 studies) undergoing liquid enema reduction. Air enema was superior to liquid enema for intussusception reduction. The success rate was higher without a difference in perforation rate. Limitations included heterogeneity and publication bias.


Usefulness of microRNA‑375 as a prognostic and therapeutic tool in esophageal squamous cell carcinoma.
The aim of this study was to clarify the importance of microRNA‑375 (miR‑375) expression in patients with esophageal squamous cell carcinoma (ESCC) and to examine the in vivo antitumor effects of miR‑375 in a model of ESCC using a non‑viral delivery system. We estimated the miR‑375 and LDHB and AEG‑1/MTDH mRNA expression of the ESCC tumors from 85 patients. The correlation between the miR‑375 expression and clinicopathological features, including the prognosis, were evaluated. The presence of high miR‑375 expression was associated with lymphatic vessel invasion, while a low expression of miR‑375 significantly correlated with a poor prognosis for the 85 ESCC patients. We also found that there was a significant inverse correlation between the expression of miR‑375 and that of LDHB. Before the examination of miR‑375 in the in vivo assay, we confirmed that atelocollagen prolonged the accumulation of miRNA by using fluorescently‑labeled miRNA and an in vivo imaging system. We injected the miR‑375/atelocollagen complex or a control‑miRNA/atelocollagen complex into mice bearing TE2 and T.Tn xenografts via subcutaneous (s.c.) injections. The growth of both the TE2 and T.Tn tumors in the miR‑375 groups was significantly suppressed compared with that in the control‑miRNA groups. In addition, The LDHB mRNA expression of TE2 xenografts was significantly downregulated after miR‑375 treatment. In conclusion, it might be possible for the level of miR‑375 expression to be a utilized as a prognostic indicator for ESCC patients. The administration of miR‑375 using a non‑viral delivery might represent a powerful new treatment for ESCC.


[Social network analysis and eating disorders: a study concerning blogs].
This study is aimed at analyzing the structure of relations among blogs referring to Eating Disorders (ED). Through the use Of Social Network Analysis (SNA) we investigated both the groups and their structure in order to study the social processes within the network. A formal analysis of the ED blogs' characteristics has been carried out. This analysis provided us with information about network Centrality and Cohesion parameters. Results allow us to highlight the most relevant blogs in the network. Even if the extremely variable nature of the blogs does not allow to have a precise picture of the blogosphere referring to ED, this first attempt to apply SNA in this field allowed us to suggest interesting remarks about EBD both from the research and from the social perspective.


Scrotal haematoma following vasectomy: an unusual surgical emergency.
A 46-year-old man who underwent a vasectomy at his general practitioner presented to the emergency department at a regional hospital with a 6 h history of scrotal swelling and skin discolouration. He was haemodynamically stable on admission, with a large, dark red swelling in his scrotum. The patient was admitted to an acute surgical unit for exploration of his scrotum. Bilateral transverse incisions were made in the patient's groin, and approximately 600 mL of blood was drained from the patient's scrotum. Postoperatively, the patient performed well, and was discharged home on oral antibiotics and analgesia. The patient's scrotum healed well, and after 2 months of follow-up, he was discharged.


Genetic counseling, a health department service to physicians.
Questions about inheritance in all kinds of diseases and defects are commonly asked of nearly all physicians. In attempting to answer these questions, however, the physician is often hampered by lack of formal instruction in clinical genetics. Since the health department, if it is to carry out its epidemiologic function, must be as concerned over the increasing identification of genetic agents in disease as it is and has been over environmental disease agents, it should come to represent a source of assistance not now generally available to the physician. In short, as it carries out those activities by which its store of general genetic information is increased, and until other sources of genetic consultation become reasonably available, the health department can be of real service to physicians as a resource to which they may turn for help when dealing with families wanting genetic information. Such a service has been provided experimentally for the last two years by the Contra Costa County Health Department. This program calls for the taking of family pedigrees by public health nurses on families with questions of a genetic nature who are health department clients and on families who are referred by their private physicians for this service. An interpretation of each pedigree is made by the department's physician in charge of the program and submitted to the family's physician for his use in counseling the family. Evidence to date suggests the process can be a highly useful service to the practitioner and his patient.


Antimycins A10 approximately A16, seven new antimycin antibiotics produced by Streptomyces spp. SPA-10191 and SPA-8893.
Seven new antimycin antibiotics, named antimycins A10, A11, A12, A13, A14, A15 and A16, were isolated from the fermentation broth of strains of Streptomyces spp. SPA-10191 and SPA-8893, along with known antimycins A1, A2, A3 and A4. The structures of the new antimycins were determined by spectral analyses, including 2D NMR techniques. These compounds exhibited antifungal activity against Candida utilis.


Functional conservation of both CDS- and 3'-UTR-located microRNA binding sites between species.
MicroRNAs (miRNAs) mediate gene regulation posttranscriptionally through pairing of their seed (2-7 nt) to 3'-untranslated regions (3'-UTRs) or coding regions (coding sequences [CDSs]) of their target genes. CDS target sites generally show weaker repression effects than 3'-UTR sites. However, little is known about the conservation of the function, that is, repression effect, for these two groups of target sites. In addition, no systematic analysis of the evolutionary constraint on CDS sites exists to date. To address these questions, we performed RNA-sequencing to quantify the regulatory effect of miR-15a/miR-16 and miR-92a on their CDS and 3'-UTR targets in human and macaque cells. These miRs were knocked down transiently so the repression effect could be tracked immediately. Although on average CDS targets are less derepressed than 3'-UTR targets in both species, both the 3'-UTR targets and the CDS targets are functionally conserved. The evolutionary analysis of miRNA target sites shows that CDS sites are more conserved than nontarget control, albeit to a lesser extent than 3'-UTR sites. In conclusion, CDS target sites are functional, even though they are subject to less functional constraint than 3'-UTR target sites.


Dieting in Spanish adolescent girls.
This article examines the relation between dieting and non-dieting adolescent girls and body mass index (BMI), eating attitudes and the influence of the aesthetic body shape model. Three hundred forty-nine Spanish adolescent girls in their second year of secondary education were selected. The research design was a cross-sectional ex post facto study and validated measures were used to assess the main variables. Fourteen per cent of the sample was on a diet. Of this group, 69% were overweight, 70% had disordered eating attitudes and 70% were influenced by the current aesthetic body shape model. In all situations, the scores for dieters were significantly higher than those for non-dieters. Although there is not yet any clear consensus with regards to how adolescents interpret the term 'diet', the results indicate major differences between dieters and non-dieters and that those who self-report that they are on a diet present elements of the risk of developing eating and weight disorders.


The mTORC1 Signaling Support Cellular Metabolism to Dictate Decidual NK Cells Function in Early Pregnancy.
Cellular metabolism plays an important role in regulating both human and murine NK cell functions. However, it remains unclear whether cellular metabolic process impacts on the function of decidual NK cells (dNK), essential tissue-resident immune cells maintaining the homeostasis of maternal-fetal interface. Remarkably, we found that glycolysis blockage enhances dNK VEGF-A production but restrains its proliferation. Furthermore, levels of IFN-γ and TNF-α secreted by dNK get decreased when glycolysis or oxidative phosphorylation (OXPHOS) is inhibited. Additionally, glycolysis, OXPHOS, and fatty acid oxidation disruption has little effects on the secretion and the CD107a-dependent degranulation of dNK. Mechanistically, we discovered that the mammalian target of rapamycin complex 1 (mTORC1) signaling inhibition leads to decreased glycolysis and OXPHOS in dNK. These limited metabolic processes are associated with attenuated dNK functions, which include restricted production of cytokines including IFN-γ and TNF-α, diminished CD107a-dependent degranulation, and restrained dNK proliferation. Finally, we reported that the protein levels of several glycolysis-associated enzymes are altered and the mTORC1 activity is significantly lower in the decidua of women with recurrent pregnancy loss (RPL) compared with normal pregnancy, which might give new insights about the pathogenesis of RPL. Collectively, our data demonstrate that glucose metabolism and mTORC1 signaling support dNK functions in early pregnancy.


Sparfloxacin, an antibacterial drug.
The title compound, sparfloxacin or cis-5-amino-1-cyclopropyl-7-(3,5-dimethylpiperazin-1-yl)-6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid trihydrate, C(19)H(22)F(2)N(4)O(3).3H(2)O, is an antibacterial drug. The molecule, which crystallizes as a trihydrate, is in the zwitterionic form in the solid state. Hydrogen bonds stabilize the molecules in the lattice.


Overexpression of miR-489 enhances efficacy of 5-fluorouracil-based treatment in breast cancer stem cells by targeting XIAP.
Population of cancer stem cells (CSCs) in breast cancer is reported to be resistant to chemotherapy. Furthermore, many cases of treatment failure are induced by the chemoresistance of CSCs in breast cancer patients. Therefore, novel strategies should be explored urgently to reverse drug-resistance in breast cancer stem cells (BCSCs). In this study, we isolated and cultured the BCSCs from the T-47D and SKBR3 breast cancer cell lines. We observed significant resistance to 5-fluorouracil in BCSCs. Mechanically, we found that expression of miR-489 was decreased in BCSCs. Furthermore, overexpression of miR-489 was found to increase the cytotoxicity of 5-fluorouracil to BCSCs. XIAP, a key anti-apoptotic protein, was proved to be the target of miR-489. We found that enforced expression of XIAP through its recombinant expression vector abolished the effect of miR-489 on reversing the 5-fluorouracil resistance. On the contrary, embelin, a XIAP specific inhibitor, was found to sensitize BCSCs to 5-fluorouracil similarly with miR-489. In summary, our data demonstrate that introduction with miR-489 represents a novel strategy to enhance efficacy of 5-fluorouracil-based treatment in BCSCs.


Clinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B12-trafficking proteins ABCD4 and LMBD1.
Vitamin B12 (cobalamin (Cbl)), in the cofactor forms methyl-Cbl and adenosyl-Cbl, is required for the function of the essential enzymes methionine synthase and methylmalonyl-CoA mutase, respectively. Cbl enters mammalian cells by receptor-mediated endocytosis of protein-bound Cbl followed by lysosomal export of free Cbl to the cytosol and further processing to these cofactor forms. The integral membrane proteins LMBD1 and ABCD4 are required for lysosomal release of Cbl, and mutations in the genes LMBRD1 and ABCD4 result in the cobalamin metabolism disorders cblF and cblJ. We report a new (fifth) patient with the cblJ disorder who presented at 7 days of age with poor feeding, hypotonia, methylmalonic aciduria, and elevated plasma homocysteine and harbored the mutations c.1667_1668delAG [p.Glu556Glyfs*27] and c.1295G>A [p.Arg432Gln] in the ABCD4 gene. Cbl cofactor forms are decreased in fibroblasts from this patient but could be rescued by overexpression of either ABCD4 or, unexpectedly, LMBD1. Using a sensitive live-cell FRET assay, we demonstrated selective interaction between ABCD4 and LMBD1 and decreased interaction when ABCD4 harbored the patient mutations p.Arg432Gln or p.Asn141Lys or when artificial mutations disrupted the ATPase domain. Finally, we showed that ABCD4 lysosomal targeting depends on co-expression of, and interaction with, LMBD1. These data broaden the patient and mutation spectrum of cblJ deficiency, establish a sensitive live-cell assay to detect the LMBD1-ABCD4 interaction, and confirm the importance of this interaction for proper intracellular targeting of ABCD4 and cobalamin cofactor synthesis.


Platelet model for halothane-induced effects on nucleotide metabolism applied to malignant hyperthermia.
A relatively non-invasive screening technique using venous blood analyzed by high performance liquid chromatography (HPLC) was developed to assess the effects of halothane on platelet nucleotide metabolism. Platelets were selected for study because of their contractile characteristics and many metabolic similarities to voluntary muscle. Platelets of 22 patients who previously had a documented clinical episode of malignant hyperthermia demonstrated a significant change in their nucleotide profile due to halothane exposure compared to normal subjects and 10 patients with musculo-skeletal and metabolic disorders. These results showed 100% correlation with the skeletal muscle contracture test for malignant hyperthermia (PHB). The platelet-halothane bioassay is highly reproducible and specific for detecting malignant hyperthermia with a significant degree of expression at the time of venipuncture. The assay deserves further study as an aid to the diagnosis of the degree of malignant hyperthermia susceptibility.


Vowel sounds in words affect mental construal and shift preferences for targets.
A long tradition in sound symbolism describes a host of sound-meaning linkages, or associations between individual speech sounds and concepts or object properties. Might sound symbolism extend beyond sound-meaning relationships to linkages between sounds and modes of thinking? Integrating sound symbolism with construal level theory, we investigate whether vowel sounds influence the mental level at which people represent and evaluate targets. We propose that back vowels evoke abstract, high-level construal, while front vowels induce concrete, low-level construal. Two initial studies link front vowels to the use of greater visual and conceptual precision, consistent with a construal account. Three subsequent studies explore construal-dependent tradeoffs as a function of vowel sound contained in the target's name. Evaluation of objects named with back vowels was driven by their high- over low-level features; front vowels reduced or reversed this differentiation. Thus, subtle linguistic cues appear capable of influencing the very nature of mental representation.


[A man with slowly progressive dyspnea on exertion].
A 42-year-old man with a medical history of liver cirrhosis and portal hypertension was admitted to the hospital because of slowly progressive shortness of breath and hypoxemia. The diagnosis hepatopulmonary syndrome was confirmed by a pulmonary perfusion scan with 99m Tc-albumin. The scan showed a right-left shunt, because the 99m Tc-albumin transited the lungs and appeared in the brain, the thyroid gland, the kidneys and the spleen. The patient received a liver transplantation, which is considered the only definitive treatment.


Reuse of shale gas flowback and produced water: Effects of coagulation and adsorption on ultrafiltration, reverse osmosis combined process.
The shale gas flowback and produced water (FPW) from hydraulic fracturing in the Sichuan province of China has relatively low to moderate levels of total dissolved solids (<20 g/L) and organics (<50 mg/L of dissolved organic carbon). As such, a combined ultrafiltration (UF), reverse osmosis (RO) system can be successfully applied to desalinate this feed water with the goal of reuse. However, the concentration of influent organic matter and particulates in the UF and RO stage is high, and the overall ionic and organics composition is highly complex, so that the membrane processes do not perform well, also due to fouling. To ensure the long-term and efficient operation of the UF-RO stages, a combined pretreatment of the FPW with coagulation and adsorption was investigated. The effect of different parameters on the performance on the system was studied in detail. Overall, the coagulation-adsorption pre-treatment greatly reduced fouling of the membrane processes, thanks to the high removal rate of turbidity (98.8%) and dissolved organic carbon (86.3%). The adsorption of organic matter by powdered activated carbon was best described by the Freundlich equilibrium model, with a pseudo second-order model representing the adsorption kinetics. Also, the various ions had competitive removal rates during the adsorption step, a phenomenon reported for the first time for FPW treatment. Also, an optimal dose of activated carbon existed to maximize fouling reduction and effluent quality. The overall treatment system produced a high-quality water streams, suitable for reuse.


Extracting and analyzing ejection fraction values from electronic echocardiography reports in a large health maintenance organization.
The left ventricular ejection fraction value is an important prognostic indicator of cardiovascular outcomes including morbidity and mortality and is often used clinically to indicate severity of heart disease. However, it is usually reported in free-text echocardiography reports. We developed and validated a computerized algorithm to extract ejection fraction values from echocardiography reports and applied the algorithm to a large volume of unstructured echocardiography reports between 1995 and 2011 in a large health maintenance organization. A total of 621,856 echocardiography reports with a description of ejection fraction values or systolic functions were identified, of which 70 percent contained numeric ejection fraction values and the rest (30%) were text descriptions explicitly indicating the systolic left ventricular function. The 12.1 percent (16.0% for male and 8.4% for female) of these extracted ejection fraction values are <45 percent. Validation conducted based on a random sample of 200 reports yielded 95.0 percent sensitivity and 96.9 percent positive predictive value.


Cloning, Expression, and Structural Elucidation of a Biotechnologically Potential Alkaline Serine Protease From a Newly Isolated Haloalkaliphilic Bacillus lehensis JO-26.
An alkaline protease gene of Bacillus lehensis JO-26 from saline desert, Little Rann of Kutch, was cloned and expressed in Escherichia coli BL21 (DE3). A 1,014-bp ORF encoded 337 amino acids. The recombinant protease (APrBL) with Asp 97, His 127, and Ser 280 forming catalytic triad belongs to the subtilase S8 protease family. The gene was optimally expressed in soluble fraction with 0.2 mM isopropyl β-D-thiogalactopyranoside (IPTG), 2% (w/v) NaCl at 28°C. APrBL, a monomer with a molecular mass of 34.6 kDa was active over pH 8-11 and 30°C-70°C, optimally at pH 10 and 50°C. The enzyme was highly thermostable and retained 73% of the residual activity at 80°C up to 3 h. It was significantly stimulated by sodium dodecyl sulfate (SDS), Ca2+, chloroform, toluene, n-butanol, and benzene while completely inhibited by phenylmethylsulfonyl fluoride (PMSF) and Hg2+. The serine nature of the protease was confirmed by its strong inhibition by PMSF. The APrBL gene was phylogenetically close to alkaline elastase YaB (P20724) and was distinct from the well-known commercial proteases subtilisin Carlsberg (CAB56500) and subtilisin BPN' (P00782). The structural elucidation revealed 31.75% α-helices, 22.55% β-strands, and 45.70% coils. Although high glycine and fewer proline residues are a characteristic feature of the cold-adapted enzymes, the similar observation in thermally active APrBL suggests that this feature cannot be solely responsible for thermo/cold adaptation. The APrBL protease was highly effective as a detergent additive and in whey protein hydrolysis.


Patient-Reported Outcome Measures and Health-Related Quality-of-Life Scores of Patients Undergoing Anatomic Total Shoulder Arthroplasty.
Health-related quality-of-life (HRQoL) scores are required for cost-effectiveness and health-care value analysis. We evaluated HRQoL scores and patient-reported outcome measures (PROMs) in patients with advanced glenohumeral osteoarthritis treated with anatomic total shoulder arthroplasty to establish values of HRQoL scores that can be used for cost-effectiveness and value analysis and to assess relationships between HRQoL scores and shoulder and upper-extremity PROMs. We analyzed 143 patients (143 shoulders) with glenohumeral osteoarthritis treated with anatomic total shoulder arthroplasty; 92 patients had 1-year follow-up. Preoperative and postoperative functional outcomes were assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) score, the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) for shoulder pain and function. Health utility was assessed with the EuroQol-5 Dimensions (EQ-5D), Short Form-6 Dimensions (SF-6D), and VAS Quality of Life (VAS QoL). HRQoL score validity was determined through correlations between the PROMs and HRQoL scores. The responsiveness of HRQoL scores was measured through the effect size and the standardized response mean. There were significant improvements in all PROMs and HRQoL scores (p < 0.001) at 1 year after the surgical procedure. The changes in VAS QoL (very weak to moderate), EQ-5D (weak), and SF-6D (weak) were significantly correlated (p < 0.05) with the changes in PROMs, demonstrating comparably acceptable validity. There were large effect sizes in the VAS QoL (1.843), EQ-5D (1.186), and SF-6D (1.084) and large standardized response mean values in the VAS QoL (1.622), EQ-5D (1.230), and SF-6D (1.083), demonstrating responsiveness. The effect sizes of all PROMs were larger than those of the HRQoL scores. PROMs and HRQoL scores are not interchangeable, and studies of the cost-effectiveness and value of shoulder arthroplasty should incorporate both shoulder and upper-extremity PROMs and HRQoL scores. The findings of this study provide data on HRQoL scores that are specific to the treatment of advanced glenohumeral osteoarthritis with anatomic total shoulder arthroplasty and can be used for future cost-effectiveness and value analysis studies. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Steric effects on the catalytic activities of zinc(II) complexes containing [12]aneN3 ligating units in the cleavage of the RNA and DNA model phosphates.
A series of N-methylated mono- and di-[12]aneN(3) ligands () have been synthesized and characterized. The steric effects on the catalytic activities of their mononuclear and dinuclear zinc(ii) complexes in the cleavage of a RNA model 2-hydroxypropyl 4-nitrophenyl phosphate (HPNPP, ) and a DNA model methyl 4-nitrophenyl phosphates (MPNPP, 4) in methanol have been investigated at 25 °C. In the cleavage of phosphate catalyzed by the mononuclear complexes, derived from the N-methylation in the [12]aneN(3) backbone, the plots of k(obs)versus [Zn(II)] changed from an upward curvature to linearity with increasing level of methylation, indicating that N-methylations led to a reduction of dinuclear association that was responsible for the synergetic effect. Compared to the activities of the complex with non-methylated di-[12]aneN(3) ligand, those of the dinuclear zinc(ii) complex (Zn(2)-8), which has the two N-methyl groups, were reduced by two orders of magnitude as measured by the second-order rate constants and synergetic effect in the cleavage of both model compounds. For reactions catalyzed by the fully N-methylated dinuclear complex (Zn(2)-9), no synergetic effect was observed. Nevertheless, complex Zn(2)-8 still showed the remarkable catalytic efficiency, with rate accelerations of 10(9-10)-fold in the cleavage of each of the two phosphates relative to the background reactions, and the synergetic effects of up to 561 folds. pH jump experiments confirmed that the rate-limiting step in the cleavage of by Zn(2)-8 involved the binding process, while that in the reaction with 4 was the chemical cleavage of the P-O bond. Steric effects in the cleavage reactions were analyzed in detail and were compared with the electronic effect caused by oxy anion bridging group in the di-[12]aneN(3) ligand and also with the hydrophobic effect observed in other systems. The work has further confirmed that the combination of the cooperativity between two metal ions and a medium effect could result in excellent catalytic activities for the cleavage of phosphate diesters.


Efficient Dual siRNA and Drug Delivery Using Engineered Lipoproteoplexes.
An engineered supercharged coiled-coil protein (CSP) and the cationic transfection reagent Lipofectamine 2000 are combined to form a lipoproteoplex for the purpose of dual delivery of siRNA and doxorubicin. CSP, bearing an external positive charge and axial hydrophobic pore, demonstrates the ability to condense siRNA and encapsulate the small-molecule chemotherapeutic, doxorubicin. The lipoproteoplex demonstrates improved doxorubicin loading relative to Lipofectamine 2000. Furthermore, it induces effective transfection of GAPDH (60% knockdown) in MCF-7 breast cancer cells with efficiencies comparing favorably to Lipofectamine 2000. When the lipoproteoplex is loaded with doxorubicin, the improved doxorubicin loading (∼40 μg Dox/mg CSP) results in a substantial decrease in MCF-7 cell viability.


Arthroscopic Management of Intraarticular Screw Perforation after Surgical Treatment of an Acetabular Posterior Wall Fracture: A Case Report.
Although surgical techniques for treating acetabular fracture are evolving, the use of periacetabular screws is common, and their placement in acetabular surgery is still technically demanding. For instance, intraarticular screw perforation is a serious complication that may occur during surgical treatment of an acetabular fracture. Here, we describe the case of a 50-year-old female who experienced an intraarticular screw perforation after surgical treatment of a posterior acetabular wall fracture. Removal of the perforated screw was performed arthroscopically based on its ability to offer minimally invasive access to the hip joint. One year after removal of the screw, no radiological signs of osteoarthritic changes were observed. The patient regained normal ambulation without limitations to range of motion or hip pain. To our knowledge, this is the first report on the use of arthroscopy to treat intraarticular screw perforation after surgical treatment of an acetabular fracture.


An electrochemical sensor device for measuring blood ammonia at the point of care.
The level of ammonia in blood is relevant in a number of medical conditions. While ammonia is a marker of dysfunction, elevated ammonia is itself a serious medical emergency and can lead to significant and permanent neurological impairment if not addressed quickly. Blood ammonia testing is typically performed in the central laboratory. While a number of point of care devices have been developed, these are based on classical enzymatic or colorimetric principles and have not been widely adopted. In this work, an electrochemical sensor device was developed for measuring blood ammonia. The device was based on the deposition of polyaniline nanoparticle films onto screen printed interdigitated electrodes using inkjet printing and their integration into a polymer microfabricated device with a polytetrafluoroethylene membrane. The device required a 52µL serum sample and measured the change in impedance of the sensor with respect to air at 1kHz, 5mV rms. The device was capable of the measurement of ammonia in serum across the physiologically relevant range of 25-200µM (r2 =0.9984) and had a limit of detection of 12µM (n =3). The device showed no significant issues with common electrochemical interferences in blood. The device was also validated against a commercial spectrophotometric assay which resulted in excellent correlation (r =0.9699, p<0.0001) between both methods (n =3). When stored under desiccation, devices displayed minimal variation over time (0.64%) with respect to their impedance in air (n =12) and could be stored in desiccant for at least five months.


Hepatitis in an infant treated with octreotide for congenital hyperinsulinism.
Congenital hyperinsulinism is characterized by hypoglycemia caused by several genetic disorders of inappropriate insulin secretion. Octreotide, an analogue of somatostatin, plays a major role in the pharmaceutical treatment of this condition. A 9-month-old infant treated with octreotide developed anicteric hepatitis with no other proven cause. After the discontinuation of this drug, the liver enzymes declined rapidly. Liver function tests should be followed in patients receiving octreotide.


An enzymatic nucleic acid vertical flow assay.
Vertical flow assays have been developed in recent years addressing limitations of the lateral flow assays, including limited multiplexing capability, quantitation, and hook effect. In the present study, the first passive paper-based vertical flow assay is developed for the detection of the nucleic acid target. Horseradish peroxidase was used as an enzymatic tracer with a high potential for signal amplification. In order to achieve the best signal-to-noise ratio, different parameters of paper-based assays were optimized. The sample is heat denatured and hybridized with a specific probe to form a dual-labeled hybridization complex. A small volume of diluted sample, 12 µl, can be analyzed within 6 min on the assay in a sandwich format. Assay specificity was evaluated by testing different unrelated samples, and also, 1.7 nM was obtained as the limit of detection (LOD) using the 0 + 3SD method, which is equivalent to 8.5 fmol of double-stranded DNA in the 12 µl sample volume. The linear range of 3-194 nM with a 0.978 correlation coefficient was obtained according to the calibration curve. The developed assay was evaluated with 45 hepatitis B virus clinical plasma samples, and the result showed 100% consistency of the assay with the real-time PCR benchmark. In the present study, we sought to develop a mere detection system for nucleic acid targets, and to investigate the possibility of using enzyme reporter in a passive vertical flow assay.