Impacts of Renal Sympathetic Activation on Atrial Fibrillation: The Potential Role of the Autonomic Cross Talk Between Kidney and Heart.
Recent studies have demonstrated that there is a high variability of renal sympathetic nerve density distribution from proximal to distal renal artery segments. The aim of our study was to investigate the roles of renal sympathetic nerve stimulation (RSS) on atrial fibrillation and cardiac autonomic nervous activity. Twenty-eight dogs were randomly assigned to the proximal RSS group (P-RSS, N=7), middle RSS group (M-RSS, N=7), distal RSS group (D-RSS, N=7), and the control group (sham RSS, N=7). RSS was performed using electrical stimulation on the bilateral renal arteries for 3 hours. Effective refractory period and the window of vulnerability were measured at atrial and pulmonary veins sites. Superior left ganglionated plexi (SLGP) and left stellate ganglion (LSG) function and neural activity were determined. C-fos and nerve growth factor protein expression in the SLGP and LSG were examined. Only P-RSS (1) caused pronounced blood pressure rises, induced a significant decrease in effective refractory period, and generated a marked increase in cumulative window of vulnerability and effective refractory period dispersion; (2) increased the frequency and amplitude of the neural activity in the SLGP and LSG; (3) increased SLGP and LSG function; and (4) upregulated the level of c-fos and nerve growth factor expression in the SLGP and LSG. This study demonstrated that renal sympathetic nerve activation induced by 3 hours of P-RSS facilitated atrial fibrillation inducibility by upregulating cardiac autonomic nervous activity, suggesting a potential autonomic cross talk between kidney and heart.


Radiofrequency thermal ablation sharply increases intratumoral liposomal doxorubicin accumulation and tumor coagulation.
Combining radiofrequency (RF) ablation with i.v. liposomal doxorubicin (Doxil) increases intratumoral doxorubicin accumulation and tumor destruction. The purpose of this study was to characterize and better define the specific parameters of such treatment in an animal tumor model. Four hundred R3230 mammary adenocarcinoma nodules were implanted in 250 Fischer rats. First, paired tumors received combined standardized RF (70 degrees C +/- 2 degrees C, 5 min) followed 30 min later with i.v. Doxil (1 mg) or Doxil alone. Intratumoral doxorubicin uptake was evaluated using fluorospectrophotometry 2-120 h after therapy (n = 110). The effects of varying i.v. Doxil doses (0.0625-7.0 mg; n = 100) and the RF tip temperatures (45 degrees C-90 degrees C; n = 190) on subsequent intratumoral doxorubicin uptake and induced tumor necrosis were evaluated. Intratumoral doxorubicin accumulation increased to a maximum at 72 h with greater uptake in the RF-ablated tumors compared with controls (P < 0.01). Greater dose-dependent intratumoral doxorubicin increases (to 37.3 +/- 7.7 microg/g) were seen with combined RF/Doxil therapy (P < 0.01). RF ablation reduced the i.v. Doxil dose needed to achieve intratumoral doxorubicin uptake of 13 microg/g from 7 to 2 mg. Increasing tip temperatures from 50 degrees C to 90 degrees C increased the ratio of doxorubicin in RF to nonablated tumors from 1.2 +/- 0.4 to 5.9 +/- 3.8 (P < 0.01). At all temperatures, greater tumor necrosis was identified for RF/Doxil-treated tumors compared with tumors treated with RF alone (P < 0.05). The threshold for inducing necrosis was 5 degrees C lower for tumors receiving combined therapy (P < 0.01). RF tumor ablation sharply increases intratumoral Doxil accumulation over i.v. Doxil alone, enabling a reduction of systemic dose while obtaining higher intratumoral concentrations than otherwise achievable. Combined therapy also increases tumor destruction over either therapy alone.


Nucleic Acid Amplification by Template-Dominated Click Chemistry for Ultrasensitive DNA/RNA Detection on an Electrochemical Readout Platform.
As an enzyme-free exponential nucleic acid amplification method, the click chemistry-mediated ligation chain reaction (ccLCR) has shown great prospects in the molecular diagnosis. However, the current optics-based ccLCR is challenged by remarkable nonspecific amplification, severely hindering its future application. This study demonstrated that the severe nonspecific amplification was generated probably due to high random collision in the high DNA probe concentration (μM level). To solve this hurdle, a nucleic acid template-dominated ccLCR was constructed using nM-level DNA probes and read on an electrochemical platform (cc-eLCR). Under the optimal conditions, the proposed cc-eLCR detected a low-level nucleic acid target (1 fM) with a single-base resolution. Furthermore, this assay was applied to detect the target of interest in cell extracts with a satisfactory result. The proposed cc-eLCR offers huge possibility for click chemistry-mediated enzyme-free exponential nucleic acid amplification in the application of medical diagnosis and biomedical research.


[Ivermectin and human onchocerciasis. A study of 234 onchocerciasis patients in the Republic of Mali].
In a double blind study Ivermectin has been compared to a placebo in 234 male and female with onchocerciasis who had more than 20 microfilariae per milligram of skin and moderate ocular involvement. Patient was randomized to receive a simple oral dose of Ivermectin 100, 150 and 200 micrograms/kg or placebo. The following was 12 months. The decrease of microfilarodermia since to the 3rd day was from 72.8 to 79.3% of initial rate. At six months it was more than 91% and more than 87% in 12 months. Ocular microfilariae, initially between 12 and 23 stay lower than 2 at 12 months. Punctuated keratitis disappear and did not recidive still 6 months in patients with persistent microfilariae. Ivermectin produce only few side effects. Negative waves have been observed on ECG but without any clinical signs. The Power efficient dose seen to be 100 micrograms/kg.


Proposal of in situ density calibration for Thomson scattering measurement by microwave reflectometry.
A density calibration using microwave reflectometry for a Thomson scattering measurement is proposed. The calibration can be performed in parallel with a plasma experiment. A compact and simple FM-type reflectometer is preferable due to the small space around the Thomson scattering device. A Bayesian estimation method is also proposed for the derivation of the calibration factor. The Bayesian method requires fewer data from the reflectometer than an average method for an accurate density calibration factor, which is confirmed by a Monte Carlo simulation.


Performance of ceramic disk filter coated with nano ZnO for removing Escherichia coli from water in small rural and remote communities of developing regions.
Global water safety is facing great challenges due to increased population and demand. There is an urgent need to develop suitable water treatment strategy for small rural and remote communities in low-income developing countries. In order to find a low-cost solution, the reduction of E. coli using ceramic water disk coated with nano ZnO was investigated in this study. The performance of modified ceramic disk filters was influenced by several factors in the filter production process. Based on the factorial analysis, the pore size of the disk filters was the most significant factor for influencing E. coli removal efficiency and the clay content was the most significant one for influencing flow rate of modified disk filters. The coating of nano ZnO led to the change of disk filter surface and porosity. The reduction of E. coli could be attributed to both filter retention and photocatalytic antibacterial activity of nano ZnO. The effects of filter operation factors including initial E. coli concentration, illumination time and lamp power on E. coli removal effectiveness were also revealed. The results can help find a safe and cost-effective approach to solve drinking water problems in small rural and remote communities of developing regions.


An assessment of incomplete facial Basal cell carcinoma excision.
To determine the rate and cause(s) of incomplete excision of basal cell carcinoma, occurring on face. A non-interventional, descriptive study. Plastic Surgery Unit, Hayatabad Medical Complex, Peshawar, from January 2002 to March 2004. Patients with basal cell carcinoma of the face reporting to the OPD were included in the study and were booked for surgery. After excision, all tumors specimens were marked at 12 o'clock and sent to laboratory for histopathology to confirm the diagnosis and to know the completeness/incompleteness of tumor excision. If biopsy reported residual tumor in any of the margins it was noted and projected as percentage for the purpose of our results. Out of 56 patients, 49 (87.5%) had complete excision of tumor. Six (10.7%) had residual tumor while in one (1.7%) patient, biopsy report failed to mention the involvement/clearance of margins. Six patients with residual tumor were given postoperative radiotherapy. All patients were followed for a minimum of 2-1/2 years (critical period for recurrence) with careful watch on those with residual tumor. So far, only 2 of these 6 had recurrence of lesion. Both of them were greater than 2 cm in diameter and were located on medial canthal and nasolabial region. Chances of incomplete tumor excision are more on the mid face region. Patients with residual tumor are more prone to recurrence.


Optimization of beam parameters and treatment planning for intensity modulated proton therapy.
One of the objectives of the ongoing research and development work at the Northeast Proton Therapy Center (NPTC) in Boston is to perform optimized intensity modulated proton therapy (IMPT) treatments. Such treatments may be delivered by magnetically scanning a narrow proton pencil beam across the target volume, while both the scanning speed and the intensity of the beam are modulated. Localization of the proton dose in space allows one to yield dose distributions that are highly conformal to the target volume, thus minimizing the dose delivered to the surrounding healthy tissue. The aim of the current research is to determine technically optimal and clinically relevant specifications for the scanned beam delivery system, which is being developed in collaboration with Ion Beam Applications (IBA); and to create a link between the treatment planning and the beam delivery. IMPT treatment planning is performed for patient cases treated at the NPTC, with KonRad Pro software developed at the German Cancer Research Center (DKFZ). For the IMPT delivery, the proton intensity maps, optimized for discrete pencil beam spots, need to be translated into continuous scanning patterns. At the same time it is necessary to minimize the discrepancy between the planned and delivered doses which may result from such conversion, as well as from the technical limitations of the delivery system. Possibilities have been investigated for improving the proton dose conformity by optimizing the beam and scanning nozzle parameters, and by taking the specifics and limitations of the system into account in the treatment planning stage.


Altered exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of cultured striatal neurons in a knock-in mouse model of Huntington's disease.
Huntington's disease (HD) is a progressive dominantly inherited neurodegenerative disease caused by the expansion of a cytosine-adenine-guanine (CAG) trinucleotide repeat in the huntingtin gene, which encodes the mutant huntingtin protein containing an expanded polyglutamine tract. One of neuropathologic hallmarks of HD is selective degeneration in the striatum. Mechanisms underlying selective neurodegeneration in the striatum of HD remain elusive. Neurodegeneration is suggested to be preceded by abnormal synaptic transmission at the early stage of HD. However, how mutant huntingtin protein affects synaptic vesicle exocytosis at single presynaptic terminals of HD striatal neurons is poorly understood. Here, we measured synaptic vesicle exocytosis at single presynaptic terminals of cultured striatal neurons (mainly inhibitory neurons) in a knock-in mouse model of HD (zQ175) during electrical field stimulation using real-time imaging of FM 1-43 (a lipophilic dye). We found a significant decrease in bouton density and exocytosis of synaptic vesicles at single presynaptic terminals in cultured striatal neurons. Real-time imaging of VGAT-CypHer5E (a pH sensitive dye conjugated to an antibody against vesicular GABA transporter (VGAT)) for inhibitory synaptic vesicles revealed a reduction in bouton density and exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of HD striatal neurons. Thus, our results suggest that the mutant huntingtin protein decreases bouton density and exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of striatal neurons, causing impaired inhibitory synaptic transmission, eventually leading to the neurodegeneration in the striatum of HD.


Phase Diagram of Pickering Emulsions Stabilized by Cellulose Nanocrystals.
Cellulose is a promising renewable and biocompatible biopolymer for stabilizing Pickering emulsions (PEs). In the present study, PEs were produced by low-frequency ultrasounds with cellulose nanocrystals (CNCs) and caprylic/capric triglycerides. Phase diagrams allowed to understand mechanisms of formation and long-term stabilization of PEs. Emulsion type, continuous phase viscosity, and yield of oil incorporation were studied after PEs formation. Droplet size, oil release, and stability were measured weekly up to 56 days of storage. Results showed that oil mass fraction above 70% w/w led to unstable W/O PEs. Lower oil mass fraction formed O/W PEs of stability depending on CNC content and oil mass fraction. Droplet size stability increased with CNCs/oil ratio. A very low CNCs/oil ratio led to phase separation and oil release. High CNC content stabilized oil droplets surface, increased aqueous phase viscosity, and prevented creaming. Highly stable PEs were produced for CNC content above 3% (w/w) and oil mass fraction below 50% (w/w). Mechanisms for PEs formation and stabilization were proposed for various CNC contents and oil mass fractions.


Surfactant protein A and D (SP-A, AP-D) levels in patients with septic ARDS.
The levels of surfactant protein-A (SP-A) and surfactant protein-D (SP-D) in the serum of patients with septic acute respiratory distress syndrome (ARDS) were determined. Patients with sepsis without ARDS were examined as controls. The mean serum SP-A level in the former group was 37.6 +/- 16.2 ng/ml and in the latter group was 31.8 +/- 9.6 ng/ml. The difference between the two groups was not statistically significant. The maximum serum SP-D level was 83.0 +/- 33.9 ng/ml in the control group of patients without ARDS, and 476.3 +/- 391.2 ng/ml in the patients with ARDS. The level in the latter population was significantly higher than that in the former population. No significant correlation was observed between the SP-A and SP-D levels. These results suggest that the serum SP-D levels may serve as a good diagnostic indicator of ARDS in patients with sepsis.


[Eosinophilic endomyocarditis post partum or pregnancy-related cardiomyopathy].
We report the case of a 28-year old asthmatic female patient, who developed an acute heart failure beginning with diarrhea, fever, and dyspnea 5 weeks after delivery. After improvement of all vital functions and dismissal from hospital care unit a marked blood hypereosinophilia, left ventricular congestive heart failure, pericardium effusion and fever up to 40 degrees C followed. Endomycardial, bone marrow and skeletal muscle biopsies and the pericardial fluid showed a marked eosinophilic infiltration or polymyositis, respectively, which could be treated successfully with steroids and azathioprin. During steroid medication cytomegalovirus-associated myocarditis developed and was diagnosed by in situ hybridization. CMV hyperimmunoglobulin treatment (Cytotect, Biotest) was started (2 ml/kg bw on day 1 and 3, and 1 ml/kg on days 5, 7 and 9), which led to the eradication of the residual infiltrate and CMV-DNA in the myocardium. After discontinuation of all medication, eosinophilia and asthma recurred so that immunosuppressive treatment was continued.


Electrical wiring of Pseudomonas putida and Pseudomonas fluorescens with osmium redox polymers.
Two different flexible osmium redox polymers; poly(1-vinylimidazole)12-[Os-(4,4'-dimethyl-2,2'-di'pyridyl)2Cl2](2+/+) (osmium redox polymer I) and poly(vinylpyridine)-[Os-(N,N'-methylated-2,2'-biimidazole)3](2+/3+) (osmium redox polymer II) were investigated for their ability to efficiently "wire" Pseudomonas putida ATCC 126633 and Pseudomonas fluorescens (P. putida DSM 6521), which are well-known phenol degrading organisms, when entrapped onto cysteamine modified gold electrodes. The two Os-polymers differ in redox potential and the length of the side chains, where the Os(2+/3+)-functionalities are located. The bacterial cells were adapted to grow in the presence of phenol as the sole source of organic carbon. The performance of the redox polymers as mediators was investigated for making microbial sensors. The analytical characteristics of the microbial sensors were evaluated for determination of catechol, phenol and glucose as substrates in both batch analysis and flow analysis mode.


Survival and Morbidities in Infants with Birth Weight Less than 500 g: a Nationwide Cohort Study.
This study aimed to investigate the survival and morbidities of infants in the Korean Neonatal Network (KNN) with birth weight (BW) < 500 g. The demographic and clinical data of 208 live-born infants with a BW < 500 g at a gestational age of ≥ 22 weeks who were treated in the neonatal intensive care units of the KNN between 2013 and 2017 were reviewed. The survival rate of the infants was 28%, with a median gestational age and BW of 243/7 weeks (range, 220/7-336/7) and 440 g (range, 220-499), respectively. Multivariable Cox proportional hazards analysis demonstrated that survival to discharge was associated with longer gestation, higher BW, female sex, singleton gestation, use of any antenatal corticosteroids, and higher Apgar scores at 5 minutes. The overall survival rates were significantly different between the BW categories of < 400 g and 400-499 g. However, there was no significant difference in the incidence of any morbidity between the BW groups. Half of the deaths of infants with BW < 500 g occurred within a week of life, mainly due to cardiopulmonary and neurologic causes. The major causes of death in infants after 1 week of age were infection and gastrointestinal disease. Among the surviving infants, 79% had moderate to severe bronchopulmonary dysplasia, 21% underwent surgical ligation of patent ductus arteriosus, 12% had severe intraventricular hemorrhage (grade III-IV), 38% had sepsis, 9% had necrotizing enterocolitis (stage ≥ 2), and 47% underwent laser treatment for retinopathy of prematurity. The median length of hospital stay was 132 days (range, 69-291), and 53% required assistive devices at discharge. Despite recent advances in neonatal intensive care, the survival and morbidity rates of infants with BW < 500 g need further improvement.


Immunogenicity and protective efficacy of recombinant Bacille Calmette-Guerin strains expressing mycobacterium antigens Ag85A, CFP10, ESAT-6, GM-CSF and IL-12p70.
This study aimed to evaluate the immunogenicity and protective efficacy of recombinant bacille calmette-guerin (rBCG) strains expressing Ag85A (A), CFP10 (C), ESAT6 (E), IL-12p70 (I), and fusion protein GM-CSF (G). rBCGs were established by integrating of A, C, E, I, G, AE, CE, IE, GC, GE and GCE into Mycobacterium bovis BCG-1173 and BCG-SH. The macro-effects of rBCGs on mice were evaluated by phenotype and weight. The immunogenicity of rBCGs was analyzed by lgG, lgG1 and lgG2a antibody titers, and IFN-γ and IL-4 contents through Enzyme-linked immunosorbent assay (ELISA). Meanwhile, the proportions of CD4+ and CD8+ T splenic lymphocytes were determined using flow cytometry. The protective efficacy of rBCGs was evaluated by bacterial load in spleen and lung tissues from immunized mice. rBCGs exhibited no obvious side effects on mice. The antibody titers of lgG, lgG1 and lgG2a, proportion of CD4+ and CD8+ T cells, and concentrations of IFN-γ were found to be significantly higher in multiple-gene rBCGs than that in single-gene rBCGs (P < 0.05). Bacterial load in both spleen and lung tissues from mice infected with M. tuberculosis H37Rv were significantly reduced by rBCGs. A significantly lower bacterial load was revealed in rBCG-1173:A compared with multiple-gene rBCGs (P < 0.05). Immunogenicity was better on multiple-gene rBCGs than on single-gene rBCGs, while excellent protective efficacy was exhibited on rBCG-1173:A and BCG-1173.


Hemodynamics and Vascular Hypertrophy in African Americans and Caucasians With High Blood Pressure.
Hypertension in African Americans is characterized by greater systemic vascular resistance (SVR) compared with Caucasian Americans, but the responsible mechanisms are not known. The present study sought to determine if peripheral vascular hypertrophy is a potential mechanism contributing to elevated SVR in African Americans with high blood pressure (BP). In a biracial sample of 80 men and women between the ages of 25 and 45 years, with clinic BP in the range 130/85-160/99mm Hg, we assessed cardiac output and SVR, in addition to BP. Minimum forearm vascular resistance (MFVR), a marker of vascular hypertrophy, also was assessed. SVR was elevated in African Americans compared with Caucasians (P < 0.001). Regression models indicated that age, body mass index, 24-hour diastolic BP, and ethnicity were significant predictors of SVR. There was also a significant interaction between ethnicity and MFVR in explaining SVR in the study sample. In particular, there was a significant positive association between MFVR and SVR among African Americans (P = 0.002), whereas the association was inverse and not statistically significant among Caucasians (P = 0.601). Hypertrophy of the systemic microvasculature may contribute to the elevated SVR that is characteristic of the early stages of hypertension in African American compared with Caucasians.


The effect of actinomycin D on hemopoiesis. I. Short-term effects.
The effect of in vivo administration of actinomycin D (Act D) on the hemopoietic precursor compartments and, in particular, the BFU-E, CFU-E, and erythroblast populations was investigated over a 6-day period. Daily injections of mice with 15 microgram/kg, 30 microgram/kg, and 60 microgram/kg Act D showed a dose-dependent effect. The highest dose caused an almost complete eradication of CFU-E as well as the morphologically identifiable erythroblasts. There was no appreciable reduction in BFU-E, GM-CFU, and CFU-S. These observation indicate that Act D interferes with erythropoiesis by selectively inhibiting the CFU-E compartment. The effects are not due to altered sensitivity to erythropoietin as dose response curves were similar for control and Act D-treated cells. Although a considerable reduction in CFU-E is observed and approximately 20-30% of nucleated cells are lost from the small size region, there is no displacement in the velocity sedimentation profiles either from the remaining CFU-E and nucleated cell populations or the BFU-E and GM-CFU populations.


Complete Genome Sequences of Four Avian Paramyxoviruses of Serotype 10 Isolated from Rockhopper Penguins on the Falkland Islands.
The first complete genome sequences of four avian paramyxovirus serotype 10 (APMV-10) isolates are described here. The viruses were isolated from rockhopper penguins on the Falkland Islands, sampled in 2007. All four genomes are 15,456 nucleotides in length, and phylogenetic analyses show them to be closely related.


Biocompatible Conductive Polymers with High Conductivity and High Stretchability.
Stretchable electronic materials have drawn strong interest due to their important applications in areas such as bioelectronics, wearable devices, and soft robotics. The stretchable electrode is an integral unit of stretchable systems. Intrinsically conductive polymers such as poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) can have high mechanical flexibility and good biocompatibility. However, their electrical conductivity and mechanical stretchability should be greatly improved for its applications as the stretchable electrode. Here, we report highly conductive and highly stretchable PEDOT:PSS by incorporating biocompatible d-sorbitol. d-Sorbitol can serve as both the secondary dopant and plasticizer for PEDOT:PSS. It can not only significantly improve the conductivity but also the stretchability. d-Sorbitol-PEDOT:PSS (s-PEDOT:PSS) can have a conductivity of >1000 S/cm, and the conductivity could be maintained at a strain up to 60%. The resistance of s-PEDOT:PSS remains almost constant during repeated stretching-releasing cycles. The mechanism for the stretchability improvement by d-sorbitol is ascribed to the softening of PSSH chains. d-Sorbitol can position among the PSSH chains and thus destructs the hydrogen bonds among the PSSH chains. This makes the conformational change of the PSSH chains under stress become easy and thus increases the mechanical flexibility of PEDOT:PSS. This conductivity is the highest for biocompatible intrinsically conductive polymers with high stretchability.


Pseudoaneurysms in haemophilia.
The incidence of bleeding as a result of a pseudoaneurysm in haemophilia is very low. The diagnosis should be suspected if the patient has a history of arterial trauma. Pseudoaneurysms can appear anywhere where trauma occurs. This can include arterial access for catheterization, blunt trauma or penetrating trauma. The diagnosis should be confirmed using Duplex ultrasonography, computed tomography (CT) angiogram or conventional angiogram. Many options exist for the treatment of pseudoaneurysms. Although surgery was the gold standard treatment in the past (surgical ligation with or without distal bypass), several less invasive treatment options are popular today. They include covered stent, ultrasound probe compression and ultrasound-guided thrombin injection. So far, only 14 pseudoaneurysms have been reported in patients with haemophilia: nine were located in the musculoskeletal system (four in the hand, four in the knee, one in the ankle), whereas five were non-musculoskeletal. Early diagnosis and treatment of this complication is vital. Endovascular treatment offers a minimally invasive treatment option. If arterial embolization fails to solve the pseudoaneurysm, open vascular surgery with surgical ligation with or without distal bypass should be performed. Whatever the procedure, a correct surgical haemostasis must be achieved by the infusion of factor concentrate (recombinant or plasma-derived) at the right dose and tranexamic acid. The advent of activated prothrombin complex concentrates and recombinant factor VIII (rFVIIa) has made invasive procedures possible in haemophilia patients with high-titre inhibitors.


Sex-Related 30-Day and Long-Term Mortality in Acute Myocardial Infarction Patients Treated with Percutaneous Coronary Intervention.
The data on sex as an independent risk factor for death in acute myocardial infarction (MI) patients are still contrasting. The aim was to assess how sex influences 30-day and long-term all-cause mortality in MI patients undergoing percutaneous coronary intervention (PCI). Data from 3624 MI patients undergoing PCI at our institution from January 2009 to December 2014, 30.6% were women, were analyzed. A propensity-matched analysis was performed to adjust for differences in the baseline characteristics between men and women. The effect of sex on 30-day and long-term mortality was observed. Multivariate logistic regression modeling was used for 30-day mortality and Cox regression analysis for long-term mortality. The median follow-up time was 27 months (25th, 75th percentile: 9, 48). Women had a significantly higher unadjusted 30-day (5.9% in men vs. 9.5% in women; p < 0.0001) and long-term mortality (13.5% in men vs. 19.0% in women; p < 0.0001). In a propensity-matched analysis, female sex was not associated with a higher 30-day (adjusted odds ratio: 1.46; 95% confidence interval: 0.97-2.19) or long-term mortality (hazard ratio 1.02; 95% CI 0.81-1.28). Age older than 77 years, cardiogenic shock, PCI of left anterior descending artery (LAD), thrombolysis in myocardial infarction (TIMI) flow less than 3 after PCI, hypertension, dyslipidemia, and P2Y12 receptor antagonists were identified as independent predictors of 30-day and long-term mortality. In addition, renal failure requiring dialysis predicted long-term mortality. Older age, comorbidities, worse clinical presentation, and adjunctive pharmacotherapy rather than sex may explain the higher mortality rate in women with MI undergoing PCI.


[Laryngotracheitis, recurrent laryngotracheitis and asthma in children: features of ontogenesis and feeding in the first months of life].
Objective of research was to study features of ontogenesis and feeding in the first months of life in children with laryngotracheitis (LT), recurrent laryngotracheitis (RLT) and asthma. Questionnaire-based survey was performed to collect data on anamnesis of 1004 children aged 6-14 years (575 children with a history of LT, 60 children with asthma, and 369 children of control group) pertaining to preeclampsia in mothers, history of birth asphyxia, preterm birth and feeding during the first months of life in children. Children with LT were divided into two groups: 458 children with 1-3 episodes of LT and 117 children with RLT (4 or more episodes of LT). The frequency of preeclampsia among mothers of children with RLT exceeded the corresponding frequency among mothers of children with 1-3 episodes of LT and children of control group in 2.1 and 2.8 times, respectively. The frequency of birth asphyxia or preterm birth among children with RLT exceeded the corresponding frequency among children with 1-3 episodes of LT and children of control group by a factor of 2. The frequency of breastfeeding initiation after 24 hours of birth among children with asthma or RLT exceeded the corresponding frequency among children with 1-3 episodes of LT (in 1.4 and 1.5 times, respectively) and among children of control group (in 2.4 and 2.6 times, respectively). The frequency of preeclampsia in mothers, birth asphyxia, preterm birth and late initiation of breastfeeding among children with RLT exceeded the corresponding frequency among children with 1-3 episodes of LT and children of control group. There was no significant difference between the frequency of preeclampsia in mothers, birth asphyxia, initiation of breastfeeding among children with RLT and children with asthma. Formula feeding in the first months of life was equally often observed among children with LT, RLT and asthma and significantly exceeded the corresponding percentage among children in control group.


The surgical management of degenerative lumbar scoliosis. Posterior instrumentation alone versus two stage surgery.
Twenty-one patients who underwent surgery for degenerative scoliosis were retrospectively reviewed. Eleven patients underwent staged anterior and posterior surgery. Ten patients had a single posterior procedure. Posterior instrumentation to the sacrum was done in all cases. Average length of follow-up was 3.8 years (range: 2 to 7 years). All patients were assessed by the Oswestry Disability Questionnaire and Low-Back Outcome Score. Additional questions included analogue scales for pain and quality of life, and self-rating of the outcome of treatment. Nine patients that had two stage surgery and 4 patients that had single posterior surgery considered their outcome to be good or excellent (p = 0.13). This correlated with better functional tolerance, specifically sleep, lifting, sitting, and social life. Although pain intensity was the same for both groups, only the staged group reported significant reduction in analgesic intake. Significant correction in scoliosis and the lumbosacral fractional curve was noted only following staged surgery. A solid spinal fusion determined a satisfactory outcome irrespective of the method of treatment. Staged anterior and posterior surgery for degenerative lumbar scoliosis resulted in a better fusion rate, greater correction of deformity, and more improvement in function than did posterior surgery alone.


The attenuating effects of 1,2,3,4,6 penta-O-galloyl-β-d-glucose on inflammatory cytokines release from activated BV-2 microglial cells.
Alzheimer's disease (AD) is the most common cause of neurodegeneration and dementia in the elderly. Dysregulated, chronic activation of microglia, the brain's resident macrophages, induces the release of excessive amounts of pro-inflammatory cytokines which has been implicated in the early stages of AD pathology. Therefore, suppressing the expression of these inflammatory mediators may decrease or delay the progression of AD. Many natural compounds derived from plants have shown anti-inflammatory activity. The naturally occurring 1,2,3,4,6 Penta-O-Galloyl-β-d-Glucose (PGG), is a polyphenolic compound highly enriched in Rhus chinensis Millplant. It is a potent anti-inflammatory agent that act through the inhibition of many cytokines in different experimental models. In the present study, we investigated the role of PGG as an anti-inflammatory agent in LPS/IFNγ activated BV-2 microglia cells. Mouse cytokine antibody arrays were used to assess the effect of PGG on the release of pro-inflammatory cytokines, and ELISA experiments were performed to validate the results from the arrays. The results obtained from the cytokine arrays, and ELISA assays showed that PGG decreased the expression of monocyte chemotactic protein-5 (MCP-5) 8-fold, and pro-matrix metalloproteinase 9 (Pro MMP-9) 10-fold. Both of these cytokines are upregulated during the inflammatory process and have been shown to be involved in brain injury, inflammation, and neurodegeneration. Therefore, these findings suggest that the anti-inflammatory effect of PGG on activated microglia involving the attenuation of MCP-5 and Pro MMP-9 cytokines.


Polymerase Chain Transcription: Exponential Synthesis of RNA and Modified RNA.
There is increasing demand for RNA and modified RNA oligonucleotides, but in contrast to DNA oligonucleotides, they are typically prohibitively expensive to chemically synthesize, and unlike longer RNAs, they are only inefficiently produced by in vitro transcription, especially when modified. To address these challenges, we previously reported the evolution of a thermostable DNA polymerase, SFM4-3, that more efficiently accepts substrates with 2'-substituents. We now show that SFM4-3 efficiently transcribes RNA or 2'-F-modified RNA and that it also efficiently PCR amplifies oligonucleotides of mixed RNA and DNA composition. In addition, with thermocycling and the use of a novel DNA template, we demonstrate a polymerase chain transcription (PCT) reaction that results in the exponential production of orders of magnitude more RNA or modified RNA than is available by conventional transcription. PCT is more efficient and general than conventional transcription and can produce large amounts of any RNA or modified RNA oligonucleotide at a fraction of the cost of chemical synthesis.


Genomic instability of human mammary epithelial cells overexpressing a truncated form of EMSY.
The EMSY gene encodes a protein that interacts with Brca2 and is amplified in some sporadic cases of human breast cancer. To examine whether overexpression of EMSY would mimic the chromosome instability phenotype that is associated with the loss of Brca2 function, we constructed a lentiviral vector (Lenti-EMSY/GFP) that encodes a truncated form of the Emsy protein, including its Brca2-interacting domain, and green fluorescent protein (GFP) and used it to transduce human telomerase-immortalized human breast epithelial (184-hTert) cells, which have a nearly normal karyotype. At passage 5 after transduction, 39 (26%) of 150 EMSY/GFP-transduced metaphase cells contained at least one structural chromosomal abnormality compared with 19 (13%) of 150 GFP-transduced metaphase cells (P = .003, chi-square test); at passage 10, the corresponding frequencies were 42% and 15%, respectively (P < .001). Mitomycin C also produced a severalfold higher frequency of chromosome breaks in the EMSY/GFP-transduced cells than in the control cells. These results support the hypothesis that EMSY overexpression can play a role in the genesis of human breast cancer.


Transport of maternal LDL and HDL to the fetal membranes and placenta of the Golden Syrian hamster is mediated by receptor-dependent and receptor-independent processes.
Maternal lipoproteins provide nutrients to the fetus via the placenta, yolk sac, and uterine membrane plus decidua. To determine the transport processes that are responsible for the removal of lipoproteins from the maternal circulation, we measured the clearance rates of maternal LDL and HDL in vivo, as well as the tissue distribution of expression of the LDL receptor, glycoprotein 330 (gp330) and the newly described HDL receptor, SR-BI, in the placenta, yolk sac, and uterine membrane plus decidua at mid- and late-gestation of the hamster. In mid-gestation (day 10.5), LDL clearance rates of the placenta and yolk sac were similar to those in the liver (approximately 100 microl/h per g) and higher than those in the decidua (18 +/- 3 microl/h per g). Clearance rates for HDL-apoA-I and HDL-cholesteryl ether were similar to those of LDL in the placenta and decidua whereas rates in the yolk sac were dramatically higher (>1700 microl/h per g). Additionally, albumin was cleared in the placenta and decidua at approximately 16 microl/h per g whereas the yolk sac cleared the protein at much higher rates (196 +/- 22 microl/h per g). Low levels of LDL receptor were detected by immunoblot analysis in the placenta with trace amounts in the yolk sac. Gp330 and SR-BI were both barely detectable in the placenta but were expressed at high levels in the yolk sac. As gestation progressed to day 14.5, LDL and HDL clearance rates decreased in all three tissues; immunodetectable LDL receptor decreased in the placenta whereas the expression of gp330 and SR-BI in the placenta and yolk sac remained relatively constant. These data suggest that the clearance of maternal lipoproteins by the placenta, yolk sac, and decidua are mediated by receptor-mediated as well as receptor-independent processes.


Evaluation of the Waters MassTrak LC-MS/MS Assay for Tacrolimus and a Comparison to the Abbott Architect Immunoassay.
Tacrolimus (Prograf, Advagraf, and FK-506) is the most commonly prescribed calcineurin inhibitor after kidney and liver transplantation. The use of tacrolimus (in conjunction with other drugs) has successfully contributed to the maintenance of solid organ allografts; however, it also exhibits toxic side effects. Therapeutic drug monitoring of tacrolimus is used as an aid to achieve drug concentrations within a narrow therapeutic window. The Waters MassTrak Immunosuppressants assay (LC-MS/MS) for the quantification of tacrolimus in whole blood was evaluated for precision, linearity, lower limit of quantification, matrix effects, and accuracy. A method comparison with the Abbott Architect Tacrolimus immunoassay was also performed. The mean concentration (nanograms per milliliter) and coefficient of variation for low, mid, and high patient pools were 0.6% ± 19.9%, 16.0% ± 5.4%, and 31.2% ± 5.8%, respectively. The MassTrak assay was linear from 0.5 to 30.0 ng/mL. Although the MassTrak and Architect assays correlated well (R = 0.97) for patient samples, the MassTrak assay displayed an average negative bias of 18.5% versus Architect (range of 0.0%-36.7%). Analysis of a certified tacrolimus reference material in human whole blood [European Reference Materials (ERM)-DA110a, LGC Standards] on both platforms failed to completely explain the observed difference for patient samples. Two widely used assays for therapeutic drug monitoring of tacrolimus are not in agreement with one another. Care should be exercised when interpreting results generated on these 2 assay platforms.


Antioxidant Properties of Probiotic Bacteria.
Oxidative stress defines a condition in which the prooxidant-antioxidant balance in the cell is disturbed, resulting in DNA hydroxylation, protein denaturation, lipid peroxidation, and apoptosis, ultimately compromising cells' viability. Probiotics have been known for many beneficial health effects, and the consumption of probiotics alone or in food shows that strain-specific probiotics can present antioxidant activity and reduce damages caused by oxidation. However, the oxidation-resistant ability of probiotics, especially the underling mechanisms, is not properly understood. In this view, there is interest to figure out the antioxidant property of probiotics and summarize the mode of action of probiotic bacteria in antioxidation. Therefore, in the present paper, the antioxidant mechanisms of probiotics have been reviewed in terms of their ability to improve the antioxidant system and their ability to decrease radical generation. Since in recent years, oxidative stress has been associated with an altered gut microbiota, the effects of probiotics on intestinal flora composition are also elaborated.


Perinatal complications of assisted reproduction.
The main perinatal complications of assisted reproduction include congenital malformation, chromosomal aberrations, multiple pregnancy, and prematurity. Earlier studies and in vitro fertilization (IVF) registries showed that there was no increased incidence of congenital malformations in children conceived by IVF/intracytoplasmic sperm injection (ICSI). However, a large Australian study has found that by one year of age, the incidence of congenital malformations in IVF/ICSI children is increased in comparison with those naturally conceived. Several investigators found a slight but increased risk of chromosomal aberrations in ICSI children. Multiple pregnancy is a major cause of increased perinatal mortality due to increased incidence of both prematurity and congenital malformations. Even in singleton pregnancies conceived by assisted reproductive technologies, the risk of prematurity and newborns small for gestational age is increased. In this article, recently published work on perinatal complications associated with assisted reproductive technologies is reviewed.


A novel polyaspartic acid derivative with multifunctional groups for scale inhibition application.
Polyaspartic acid is a green biodegradable antiscalant and widely applied in water treatment field. However, its scale inhibition efficiency is not prominent, especially for calcium orthophosphate. So we introduced acylamino and hydroxyl groups simultaneously to prepare a novel polyaspartic-acid derivative (PASPTU) with multifunctional groups by the reaction of polysuccinimide with threonine and urea. The graft copolymer was analyzed by using nuclear magnetic resonance, gel permeation chromatography, thermogravimetric analyzer and Fourier transform infrared spectroscopy. Its scale inhibition performance for calcium orthophosphate, calcium sulfate and calcium carbonate was evaluated. The findings showed that the scale inhibition rates of the graft copolymer reached up to 100% for calcium orthophosphate, 100% for calcium sulfate and 91% for calcium carbonate at certain dosages. The findings above showed that the copolymer had excellent scale inhibition efficiency for calcium salts in water treatment processes.


The history, fungal biodiversity, conservation, and future perspectives for mycology in Egypt.
Records of Egyptian fungi, including lichenized fungi, are scattered through a wide array of journals, books, and dissertations, but preliminary annotated checklists and compilations are not all readily available. This review documents the known available sources and compiles data for more than 197 years of Egyptian mycology. Species richness is analysed numerically with respect to the systematic position and ecology. Values of relative species richness of different systematic and ecological groups in Egypt compared to values of the same groups worldwide, show that our knowledge of Egyptian fungi is fragmentary, especially for certain systematic and ecological groups such as Agaricales, Glomeromycota, and lichenized, nematode-trapping, entomopathogenic, marine, aquatic and coprophilous fungi, and also yeasts. Certain groups have never been studied in Egypt, such as Trichomycetes and black yeasts. By screening available sources of information, it was possible to delineate 2281 taxa belonging to 755 genera of fungi, including 57 myxomycete species as known from Egypt. Only 105 taxa new to science have been described from Egypt, one belonging to Chytridiomycota, 47 to Ascomycota, 55 to anamorphic fungi and one to Basidiomycota.


The chemistry and biology of unusual DNA structures adopted by oligopurine.oligopyrimidine sequences.
A family of unusual DNA structures has been discovered in segments with predominantly purines in one strand (pur.pyr sequences). These sequences are overrepresented in eukaryotic DNA and have been mapped near genes and recombination hot spots. When cloned into recombinant plasmids, many pur.pyr sequences are reactive to chemical and enzymic probes that are generally specific for single-stranded DNA. An intramolecular triplex is adopted by mirror repeats of G's and A's. Other non-B DNA structures adopted by similar sequences remain to be fully clarified but may be a family of related conformations. It is likely that these unorthodox structures play an important role in the function of the eukaryotic genome.


Molecular mechanisms of neurodegeneration mediated by dysfunctional subcellular organelles in transmissible spongiform encephalopathies.
Transmissible spongiform encephalopathies refer to a group of infectious neurodegenerative diseases with an entirely novel mechanism of transmission and pathophysiology including synaptic damage, dendritic atrophy, vacuolization, and microglial activation. Extensive neuronal loss is the main cause of chronic brain deterioration and fatal outcome of prion diseases. As the final outcome of pathological alterations, neuronal death is a prominent feature of all prion diseases. The mechanisms responsible for prion diseases are not well understood. A more comprehensive understanding of the molecular basis of neuronal damage is essential for the development of an effective therapy for transmissible spongiform encephalopathies and other neurodegenerative diseases sharing similar features. Here, we review the molecular mechanisms of mitochondrial dysfunction and endoplasmic reticulum stress-mediated neuronal death, which play crucial roles in the pathogenisis of prion diseases.


Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias.
Dysregulation of apoptosis is important in carcinogenesis. To analyse the potential inactivation of the DAP kinase/p14/HDM2/p53/Apaf-1 pathway by aberrant promoter methylation in acute leukaemias. Of five leukaemic lines examined, p14 was unmethylated in Raji, HL60 and U937, but completely deleted in Jurkat and NB4. DAP kinase was totally methylated in Raji and NB4, but unmethylated in HL60, Jurkat and U937. Apaf-1 was unmethylated in all the lines. At diagnosis, DAP kinase methylation occurred in eight (25%) APL patients and none of the other AML patients (8/32 vs 0/50, p = 0.001). DAP kinase methylation was detected in four (16%) ALL patients. p14 and Apaf-1 methylation was not detected in any of the 32 cases of acute promyelocytic leukaemia (APL), 50 cases of other subtypes of acute myeloid leukaemia (AML), and 25 cases of acute lymphoblastic leukaemia. Among AML subtypes, DAP kinase is preferentially hypermethylated in APL.


RLP, a novel Ras-like protein, is an immediate-early transforming growth factor-beta (TGF-beta) target gene that negatively regulates transcriptional activity induced by TGF-beta.
We have described previously the use of microarray technology to identify novel target genes of TGF-beta (transforming growth factor-beta) signalling in mouse embryo fibroblasts deficient in Smad2 or Smad3 [Yang, Piek, Zavadil, Liang, Xie, Heyer, Pavlidis, Kucherlapati, Roberts and Böttinger (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 10269-10274]. Among the TGF-beta target genes identified, a novel gene with sequence homology to members of the Ras superfamily was identified, which we have designated as RLP (Ras-like protein). RLP is a Smad3-dependent immediate-early TGF-beta target gene, its expression being induced within 45 min. Bone morphogenetic proteins also induce expression of RLP, whereas epidermal growth factor and phorbol ester PMA suppress TGF-beta-induced expression of RLP. Northern-blot analysis revealed that RLP was strongly expressed in heart, brain and kidney, and below the detection level in spleen and skeletal muscles. At the protein level, RLP is approx. 30% homologous with members of the Ras superfamily, particularly in domains characteristic for small GTPases. However, compared with prototypic Ras, RLP contains a modified P-loop, lacks the consensus G2 loop and the C-terminal prenylation site and harbours amino acid substitutions at positions that render prototypic Ras oncogenic. However, RLP does not have transforming activity, does not affect phosphorylation of mitogen-activated protein kinase and is unable to bind GTP or GDP. RLP was found to associate with certain subtypes of the TGF-beta receptor family, raising the possibility that RLP plays a role in TGF-beta signal transduction. Although RLP did not interact with Smads and did not affect TGF-beta receptor-induced Smad2 phosphorylation, it inhibited TGF-beta-induced transcriptional reporter activation, suggesting that it is a novel negative regulator of TGF-beta signalling.


Expanding co-payment for methadone maintenance services in Vietnam: the importance of addressing health and socioeconomic inequalities.
Ensuring high enrollment while mobilizing resources through co-payment services is critical to the success of the methadone maintenance treatment (MMT) program in Vietnam. This study assessed the willingness of patients to pay (WTP) for different MMT services delivery models and determined its associated factors. A facility based survey was conducted among 1016 MMT patients (98.7% male, 42% aged 35 or less, and 67% living with spouse) in five MMT clinics in Hanoi and Nam Dinh province in 2013. Socioeconomic, HIV and health status, history of drug use and rehabilitation, and MMT experience were interviewed. WTP was assessed using contingent valuation method, including a set of double-bounded binary questions and a follow-up open-ended question. Point and interval data models were used to estimate maximum willingness to pay. 95.5% patients were willing to pay for MMT at the monthly mean price of US$ 32 (95%CI = 28-35). Higher WTP was associated with higher level of educational attainment, higher income, male sex, and had high expenses on opiates prior to MMT. Patients who reported having any problem in Pain/ Discomfort, and who did not have outpatient care last year were willing to pay less for MMT than others. High level of WTP supports the co-payment policies as a strategy to mobilize resources for the MMT program in Vietnam. However, it is necessary to ensure equalities across patient groups by acknowledging socioeconomic status of different settings and providing financial supports for disadvantaged patients with severe health status.


In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression.
Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX's predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.


[Experiences with closed irrigation-suction drainage and simultaneous administration of an antiseptic].
In 47 patients a closed instillation drainage system was used with concomitant systemic antibiotic therapy. The schedule was strictly followed and is described in detail in the text. Prerequisites for a successful therapy are thorough surgical débridement, good coverage with soft tissue and a very careful skin closure. We propose a shortened duration of instillation of 3 to a maximum of 5 days. The Draintec suction pumps now used evidently create less problems than the classic pumps. During a mean follow-up of 3 years a definite recurrence was observed in two cases and a possible recurrence in one. In view of these results we consider this mode of treatment is still valid. Lavasept was added as an antiseptic drug in three quarters of the cases and was tolerated well. In view of the low rate of recurrence in all cases its potential cannot yet be fully estimated. We recommend the instillation-drainage system for use in thigh, upper arm and pelvic areas in the hands of a fully cooperating management team with some experience in the application of instillation-drainage systems.


Interaction of metronidazole with DNA repair mutants of Escherichia coli.
It has been proposed that one of metronidazole's partially reduced intermediates interacts either with DNA to exert a bactericidal effect or with water to form acetamide. To test this hypothesis we have examined the effect of metronidazole on several mutants of Escherichia coli that are defective in DNA repair. UV-susceptible RecA- and UvrB- point mutants have an increased susceptibility to metronidazole as manifested by both a decreased minimal inhibitory concentration and a greater bactericidal response to metronidazole in resting cultures. By these criteria, however, we find that UvrB- deletion mutants, which lack the ability to reduce nitrate and chlorate, are no more susceptible to metronidazole than is the wild type. We find, however, that these deletion mutants also lack the ability to reduce metronidazole and thus possibly to form its reactive species. When metronidazole's bactericidal effect is expressed in terms of the concurrent accumulation of acetamide derived from metronidazole, then all RecA- and UvrB- mutants are killed more efficiently than their wild types. The data are consistent, therefore, with metronidazole's lethal effect being mediated by a partially reduced intermediate on the metabolic pathway between metronidazole and acetamide. Defects in other aspects of the DNA repair system do not confer this increased susceptibility to the proposed intermediate. A Tag- mutant, for example, which is defective in 3-methyl-adenine-DNA glycosylase, does not have this increased susceptibility to the presumed precursor of acetamide. Thus, these results provide further support for the hypothesis that the bactericidal effect of metronidazole is mediated by a partially reduced intermediate in the metabolic conversion of metronidazole to acetamide and suggest that this intermediate interacts with DNA to produce a lesion similar to that caused by UV light.


Role of magnetoencephalography and stereo-electroencephalography in the presurgical evaluation in patients with drug-resistant epilepsy.
In selected patients with drug-resistant focal epilepsies (DRFE), who otherwise are likely to be excluded from epilepsy surgery (ES) because of the absence of a magnetic resonance imaging (MRI)-demonstrable lesion or discordant anatomo-electro-clinical (AEC) data, magnetoencephalography (MEG) may help to generate an AEC hypothesis and stereo-electroencephalography (SEEG) may help to verify the hypothesis and proceed with ES. The sensitivity of MEG is much better in localizing the spiking zone in relation to lateral temporal and extratemporal cortical regions compared to the mesial temporal structures. MEG has a dominant role in the presurgical evaluation of patients with MRI-negative DRFEs, insular epilepsies, and recurrent seizures after failed epilepsy surgeries, and in guiding placement of invasive electrodes. Moreover, postoperative seizure freedom is better if MEG spike source localized cortical region is included in the resection. When compared to subdural grid electrode recording, SEEG is less invasive and safer. Those who are otherwise destined to suffer from uncontrolled seizures and their consequences, SEEG guided ES is a worthwhile and a cost-effective option. Depending on the substrate pathology, there is > 80-90% chance of undergoing ES and 60-80% chance of becoming seizure-free following SEEG. Recent noninvasive techniques aimed at better structural imaging, delineating brain connectivity and recording specific intracerebral EEG patterns such as high frequency oscillations might decrease the need for SEEG; but more importantly, make SEEG exploration more goal-directed and hypothesis-driven.


Identification of Nramp2 as an iron transport protein: another piece of the intestinal iron absorption puzzle.
Although a number of iron-binding proteins have been identified, the roles for specific proteins in mediating iron absorption have not been definitively assigned. Two recent papers report the identification of an iron transport protein that may be responsible for movement of iron from the intestinal lumen into the enterocyte. Coupled with the recent identification of the protein mutated in hemochromatosis, researchers are now establishing a clearer picture of the mechanism of intestinal iron absorption.


Simultaneous Fifth Carpometacarpal Joint Dislocation and Fourth Metacarpal Neck Fracture: A Conservative Treated Case With a Functional Metacarpal Splint.
Simultaneous carpometacarpal joint dislocation and fractures of adjacent carpal bones are rare orthopedic injuries. With this case, we aimed to discuss the effectiveness and ergonomics of the functional metacarpal splint in carpometacarpal joint dislocations and metacarpal neck fractures without surgery. A 27-year-old right-hand dominant male applied to the emergency department after a punch on a wall with his right fist. Pain, swelling, and deformity were evident without neurovascular injury. The radiographs showed simultaneous fifth carpometacarpal joint dislocation and fracture of the neck of the fourth metacarpal bone. We performed closed reduction with longitudinal traction and applied a functional metacarpal splint. We followed up with the patient regularly, and on the fourth week, we removed the splint and began a range of motion exercises. On the sixth week, we began muscle strengthening exercises, and we reached full range of motion with fair muscle strength on the eighth week of the follow-up without any deformity. In this case, prompt diagnosis, longitudinal traction, closed reduction with manual dorsal manipulation, and functional metacarpal splinting were adequate. We achieved a full range of motion without the need to immobilize the wrist or metacarpophalangeal joints or undergo surgery after proper immobilization with a functional metacarpal splint.


Sports medicine training in Canadian paediatric residency programs: Are we doing enough?
To assess sports medicine teaching in Canadian paediatric residency programs and recent paediatric graduates' comfort level with sports medicine. Recent paediatric graduates were surveyed about the amount of sports medicine training they had received during residency, as well as their comfort level in diagnosing and managing common sports medicine problems. Paediatric residency program directors were surveyed about the sports medicine content in their programs. Survey response rates for recent graduates and program directors were 52.6% and 81.3%, respectively. Of the recent graduates who responded, 84.7% had 5 h or less of formal sports medicine teaching during residency and 94.9% had no formal clinical rotation in sports medicine. The vast majority of respondents (84.2%) were less than comfortable with their musculoskeletal anatomy knowledge; only 15.8% were comfortable. There were no significant differences between general paediatricians and subspecialists in their reported comfort level with diagnosis (P=0.938) and management (P=0.967) of sports injuries. No program provided more than 5 h of formal teaching in sports medicine, and only one program has a core sports medicine rotation. None of the responding program directors felt that new paediatricians are even somewhat prepared to provide adequate medical care for athletes, and 61.5% felt that a curriculum in sports medicine was necessary. Canadian paediatric residents had limited exposure to sports medicine, and many recent graduates were uncomfortable with their skills in sports medicine. Canadian paediatric residency programs should include a curriculum in sports medicine to adequately prepare future paediatricians to care for young athletes.


Mechanical circulatory support improves diabetic control in patients with advanced heart failure.
Left ventricular assist devices (LVADs) are increasingly being used as life-saving therapy for end-stage advanced heart failure. Diabetes is prevalent in advanced heart failure patients. In this study, we sought to investigate the effects of mechanical circulatory support on diabetic parameters with LVAD implantation. In this retrospective study, data on 244 LVAD recipients between 2006 and 2013 were reviewed. Patients without history of diabetes, death within the first 3 months after LVAD implantation, heart transplantation after LVAD, or LVAD explantation were excluded from the study. Baseline demographic, laboratory, and echocardiographic information prior to LVAD placement and 6-month follow-up were obtained. Laboratory values indicative of diabetic control were found to improve significantly at 6 months post-LVAD implantation (glycated haemoglobin, 7.2 vs. 6.1%, P < 0.0001; serum fasting glucose, 141 vs. 122 mg/dL, P = 0.003; mean daily insulin dose, 30 vs. 24 IU/day, P = 0.02). Additionally, the use of oral hypoglycaemic medication was successfully discontinued in six patients at 6 months post-LVAD implantation. Long-term LVAD therapy is associated with improvement in diabetic control which is probabvly due to improvements in cardiac output and normalization of biochemical derangements resulting from diabetes.


[Biopsy of the sentinel lymph node in the staging of patients with malignant melanoma].
Sentinel node biopsy, in the treatment of stage I and II skin melanomas (according to the American Joint Cancer Committee classification), has been advocated by several authors as the best compromise between radical intent and minimal surgical invasiveness. The authors present their personal experience based on 64 sentinel node biopsies in patients with stage I and II skin melanoma of the trunk and limbs (30 males and 34 females; age range: 29-77 years). Sentinel node detection was radio-guided and was conducted in the armpit in 43 cases and in the groin in the remaining 21. Eleven patients who presented metastatic nodes underwent a regional lymphadenectomy (8 axillary and 3 groin dissections) with low morbidity and no perioperative mortality.


Introduction: the social sciences in a cross-disciplinary age.
As studies of the history of social science since 1945 have multiplied over the past decade and a half, it has not been unusual for commentators to present cross-disciplinary ventures as a byproduct of the disciplinary system and to contrast the stability of disciplines with the highs and lows of interdisciplinary relationships. In contrast, this special issue takes the view that cross-disciplinary ventures should be considered not so much as efforts to loosen up the disciplinary yoke, but as an alternative form of production and dissemination of social scientific knowledge. Paradoxically, the relationship between cross-disciplinary ventures and the disciplinary system appears as one of complementarity and not of dependence. The essays in the special issue provide examples of ways to reconsider what can be called the interdisciplinary chaos.


Long noncoding RNA NEAT1 promotes the growth of cervical cancer cells via sponging miR-9-5p.
Evidence has accumulated demonstrating that long noncoding RNAs (lncRNAs) participate in the initiation and progression of cancers. In this study, we found that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is significantly increased in both cervical cancer tissues and cell lines. Overexpression of NEAT1 promoted the proliferation and migration of cervical cancer cells. Molecular studies uncovered that NEAT1 functions as competitive endogenous RNA (ceRNA), binding the micro-RNA miR-9-5p and suppressing its expression. However, we consistently found that when NEAT1 was highly expressed, it attenuated the inhibitory effect of miR-9-5p on the expression of PTEN and POU2F1, which are the targets of miR-9-5p. Consistent with the negative regulation of NEAT1 on miR-9-5p, restoration of miR-9-5p inhibited the growth-promoting effects of NEAT1 on cervical cancer cells. Taken together, these results indicated that NEAT1 plays an important role in the regulation cervical cancer cell growth by targeting miR-9-5p. Our findings characterized the possible mechanism of NEAT1 in cervical cancer.


Incidence of underlying biliary neoplasm in patients after major hepatectomy for preoperative benign hepatolithiasis.
Despite hepatolithiasis being a risk factor for biliary neoplasm including cholangiocarcinoma, the incidence of underlying biliary neoplasm is unknown in patients with preoperative benign hepatolithiasis. The aim of this study was to evaluate the incidence of underlying biliary neoplasm in patients who underwent major hepatectomy for preoperative benign hepatolithiasis. Between March 2005 and December 2015, 73 patients who underwent major hepatectomy for preoperative benign hepatolithiasis were enrolled in this study. The incidence and pathological differentiation of concomitant biliary neoplasm were retrospectively determined by review of medical records. Postoperative complications after major hepatectomy were evaluated. Concomitant biliary neoplasm was pathologically confirmed in 20 patients (27.4%). Biliary intraepithelial neoplasia (BIN) was detected in 12 patients (16.4%), and 1 patient (1.4%) had intraductal papillary mucinous neoplasm (IPMN), as the premalignant lesion. Cholangiocarcinoma was pathologically confirmed in 7 patients (9.6%). Preoperative imaging of the 73 patients revealed biliary stricture at the first branch of bile duct in 31 patients (42.5%), and at the second branch of bile duct in 39 patients (53.4%). Postoperative complications developed in 14 patients (19.1%). Almost all patients recovered from complications, including intra-abdominal abscess (9.6%), bile leakage (4.1%), pleural effusion (2.7%), and wound infection (1.4%). Only 1 patient (1.4%) died from aspiration pneumonia. The incidence of underlying biliary neoplasm was not negligible in the patients with hepatolithiasis, despite meticulous preoperative evaluations.


The relationship between speech recognition, behavioural listening effort, and subjective ratings.
The purpose of this study was to evaluate the reliability and validity of four subjective questions related to listening effort. A secondary purpose of this study was to evaluate the effects of hearing aid beamforming microphone arrays on word recognition and listening effort. Participants answered subjective questions immediately following testing in a dual-task paradigm with three microphone settings in a moderately reverberant laboratory environment in two noise configurations. Participants rated their: (1) mental work, (2) desire to improve the situation, (3) tiredness, and (4) desire to give up. Data were analysed using repeated measures and reliability analyses. Eighteen adults with symmetrical sensorineural hearing loss participated. Beamforming differentially affected word recognition and listening effort. Analysis revealed the same pattern of results for behavioural listening effort and subjective ratings of desire to improve the situation. Conversely, ratings of work revealed the same pattern of results as word recognition performance. Ratings of tiredness and desire to give up were unaffected by hearing aid microphone or noise configuration. Participant ratings of their desire to control the listening situation appear to reliable subjective indicators of listening effort that align with results from a behavioural measure of listening effort.


The Combination Process for Preparative Separation and Purification of Paclitaxel and 10-Deacetylbaccatin III Using Diaion® Hp-20 Followed by Hydrophilic Interaction Based Solid Phase Extraction.
There is no other naturally occurring defense agent against cancer that has a stronger effect than paclitaxel, commonly known under the brand name of Taxol®. The major drawback for the more widespread use of paclitaxel and its precious precursor, 10-deacetylbaccatin III (10-DAB III), is that they require large-scale extraction from different parts of yew trees (Taxus species), cell cultures, taxane-producing endophytic fungi, and Corylus species. In our previous work, a novel online two-dimensional heart-cut liquid chromatography process using hydrophilic interaction/ reversed-phase chromatography was used to introduce a semi-preparative treatment for the separation of polar (10-deacetylbaccatin III) and non-polar (paclitaxel) taxanes from Taxus baccata L. In this work, a combination of the absorbent (Diaion® HP-20) and a silica based solid phase extraction is utilized as a new, efficient, and cost effective method for large-scale production of taxanes. This process avoids the technical problem of two-dimensional preparative liquid chromatography. The first stage of the process involves discarding co-extractive polar compounds including chlorophylls and pigments using a non-polar synthetic hydrophobic absorbent, Diaion® HP-20. Extract was then loaded on to a silica based hydrophilic interaction solid phase extraction (silica 40-60 micron). Taxanes was eluted using a mixture of water and methanol at the optimized ratio of 70:30. Finally, the fraction containing taxanes was applied to semi-preparative reversed phase HPLC. The results revealed that using this procedure, paclitaxel and 10-DAB III could be obtained at 8 and 3 times more, respectively than by the traditional method of extraction.


Thenar motor syndrome: median mononeuropathy of the hand.
To evaluate a population with presumed carpal tunnel syndrome (CTS) for isolated involvement of the median motor nerve distal latency at or near the thenar eminence. This prospective study performed in various outpatient venues randomly selected 500 railroad workers with hand symptoms and presumed CTS entering into litigation. Electrodiagnostic studies were performed by using common techniques and distances. The dominant hand of each subject was evaluated. A prolonged median minus ulnar nerve distal latency differential (MUD) was the standard for determining CTS. Subjects with an isolated delay of motor MUD, with a normal sensory and midpalmar MUD, were classified as having thenar motor syndrome (TMS). After eliminating all subjects who did not meet the criteria of the electrodiagnostic studies, there remained a cohort of 126 subjects. There were 38 who met the criteria for TMS, and all others were classified as true CTS. Both groups were overweight, and the body mass index of the true CTS group was significantly higher (P < 0.006). TMS is a distinct electrodiagnostic entity. As an artifact of the study design (the exclusion of subjects with prior surgery), the relative frequency of TMS was increased. Aside from body mass index, no anthropometric or demographic difference between TMS and true CTS was demonstrated. Although no occupation source was identified, a possible pathogenesis includes local trauma superimposed on a common anatomic variant.


A novel prognostic model for malignant mesothelioma incorporating quantitative FDG-PET imaging with clinical parameters.
Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease. Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity. Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P < 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography-assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented. Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease.


[Social Differences in Proper Detection of Cervical Uterine Cancer among Employees at a University in Mexico City].
In Mexico, cervical uterine cancer (CUC) is one of the leading causes of death among women, however a low degree of participation in the early detection programs has been found. This study is aimed at describing the social determinants of knowledge related to cervical uterine cancer and proper testing being conducted by establishing the social differences with regard thereto among a population of female employees at a public university in Mexico. An analytical cross-sectional study was made. During the March-April 2003 period, a survey was conducted of a representative sample of the female employees who were working at a public university (n=228), 110 of whom were professors (PF) and 118 administrative staff (AS). This population was chosen due to the major socioeconomic differentiation thereof in terms of their job positions (PF versus AS), thus affording the possibility of evaluating the bearing social inequality has on health-related behavior. The survey explored three aspects: living conditions, knowledge of CUC and of proper cervical uterine cancer detection testing. The female professors showed higher levels of income,schooling and knowledge of CUC and of cervical uterine cancer detection testing than the administrative staff. Income and schooling were positively related to the knowledge regarding cervical uterine cancer, cervical uterine cancer detection testing being related to the latter. Socioeconomic inequality among the women studied was reflected in differences in the degree of knowledge and in cervical uterine cancer detection testing being undergone. These differences are associated, above all, to the differences in the level of schooling.


Genicular Radiofrequency Ablation for Treatment of Post Total Knee Arthroplasty Posterior Thigh Pain: A Case Report.
We present a case of a 68-year-old woman with 6 months of chronic unilateral posterior thigh pain after a total knee arthroplasty. The patient's pain was refractory to various treatments. After appropriate diagnostic tests, a genicular nerve block and subsequent radiofrequency ablation were performed. These procedures provided substantial pain relief of her thigh pain at 3 months follow-up.


Prognostic factors in childhood-acquired brain injury.
A long-term follow-up study comparing children after anoxic brain injury (AnBI) with those after traumatic brain injury (TBI) was conducted, and prognostic factors were mapped. A prospective historical study following long-term functional outcome after childhood brain injury was conducted in two phases. The first phase included patients suffering from moderate-severe TBI. The second phase assessed children after AnBI, and the results were compared. Functional outcome was recorded and factors influencing prognosis were outlined. On admission vegetative state (VS) was twice as prevalent in the AnBI subgroup. Approximately 90% of children with TBI and 60% of patients with AnBI gained independency in activities of daily living (ADL) and mobility. Long-term positive outcome, i.e., return to school and open-market employment, were higher in patients with TBI when compared with AnBI (61% and 48.1%, respectively). Significant outcome-predicting factors were VS at admission to rehabilitation, length of loss of consciousness (LOC) up to 11 days and functional independence measure (FIM) score at admission and discharge. Aetiology was not found to be a predicting factor. Duration of unconsciousness is the main long-term negative prognostic outcome factor. Anoxic brain damage, associated with longer periods of unconsciousness also heralds a less favourable outcome.


Social facilitation of responses during a stimulus paired with electric shock.
Key-pecking responses of a pigeon were maintained by a variable-interval schedule of food reinforcement. The responses were suppressed during the occasional presentation of a warning stimulus paired with electric shock. The presence of a second pigeon emitting the same response for food reinforcement reduced the suppression that otherwise occurred during the warning stimulus when the second pigeon was absent. These results reveal that the social facilitation phenomenon can be used to restore behavior that is suppressed by a conditioned aversive stimulus.


Substance use intervention failure: a point of view or how the cure becomes the disease or an ode to experts on incurability or masking the disease, mitigating someone's pain but providing no basic cure/solution.
Substance use intervention, both in the private and public sectors, continues to be associated with failure. This paper makes the assumption that: 1) there is a need to systematically consider and explore FAILURE in its various parameters (definitions, characteristics, forms, shapes, potencies, densities, directions, tempos, levels, phases, meanings, and adhesiveness), sources, and "demands" in the broad area of substance use intervention; 2) we can learn from failure (categorizing its processes and outcomes, selecting foci for intervention, and failure's "veracity," status, transmittability and potential/actual usability over time); and 3) we should continue to repeat this process until there is little need to do so. As times and definitions change, there will never be an end to failure or the need to learn from failure. Failure is considered as a value, and having value, on a multidimensional, dynamic gradient (minimal to maximal), being describable, discernable, catagorizable, understandable, while being-culture-site-ideologically bound/influenced. Exploring FAILURE offers us-in our various substance use intervention roles-the opportunity to learn from what we have done and to more appropiately plan, implement, and assess what we may want and/or need to know and to do. Examples are given of ongoing sources of built-in substance use intervention failure.


Large displacement vertical translational actuator based on piezoelectric thin films.
A novel vertical translational microactuator based on thin-film piezoelectric actuation is presented, using a set of four compound bend-up/bend-down unimorphs to produce translational motion of a moving platform or stage. The actuation material is a chemical-solution deposited lead-zirconate-titanate (PZT) thin film. Prototype designs have shown as much as 120 μm of static displacement, with 80-90 μm displacements being typical, using four 920 μm long by 70 μm legs. Analytical models are presented that accurately describe nonlinear behavior in both static and dynamic operation of prototype stages when the dependence of piezoelectric coefficients on voltage is known. Resonance of the system is observed at a frequency of 200 Hz. The large displacement and high bandwidth of the actuators at low-voltage and low-power levels should make them useful to a variety of optical applications, including endoscopic microscopy.


Inactivation of Clostridium difficile spore outgrowth by synergistic effects of nisin and lysozyme.
Inactivating Clostridium difficile spores is difficult, as they are resistant to heat, chemicals, and antimicrobials. However, this note describes inactivation of C. difficile spore outgrowth by incubation in a solution containing a germinant (1% (m/v) sodium taurocholate), co-germinants (1% (m/v) tryptose and 1% (m/v) NaCl), and natural antimicrobials (20 nmol·L-1 nisin and 0.2 mmol·L-1 lysozyme). Clostridium difficile spores were resistant to nisin and lysozyme but became susceptible during germination and outgrowth triggered and promoted by sodium taurocholate, tryptose, and NaCl. The degree of inactivation of germinated and outgrowing C. difficile spores by both nisin and lysozyme was greater than the sum of that by nisin and lysozyme individually, suggesting synergistic inactivation of C. difficile spores. The germinant, co-germinants, and natural antimicrobials used in this study are safe for human contact and consumption. Therefore, these findings will facilitate the development of a safe and effective method to inactivate C. difficile spore.


Prediabetes, elevated iron and all-cause mortality: a cohort study.
Data have indicated low to non-existent increased mortality risk for individuals with prediabetes, but it is unclear if the risk is increased when the patient has elevated iron markers. Our purpose was to examine the mortality risk among adults with prediabetes in the context of coexisting elevated transferrin saturation (TS) or serum ferritin. Data collected by the third National Health and Nutrition Examination Survey 1988-1994 (NHANES III) in the USA and by the National Center for Health Statistics for the National Death Index from 1988 to 2006. Individuals age 40 and older who participated in the NHANES and provided a blood sample. Mortality was measured as all-cause mortality. Adjusted analyses show that prediabetes has a small increased mortality risk (HR=1.04; 95% CI 1.00 to 1.08). Persons who had prediabetes and elevated serum ferritin had an increased HR for death (HR=1.14; 95% CI 1.04 to 1.24) compared with those who had normal ferritin and normal glucose. Among persons with prediabetes who had elevated TS, they had an increased mortality risk (HR=1.88; 95% CI 1.06 to 3.30) compared with those with normal TS levels and normal glucose. The mortality risk of prediabetes is low. However, among individuals who have coexisting elevated iron markers, particularly TS, the risk rises substantially.


Determination of NA gene frequencies in the Spanish population by polymerase chain reaction with sequence-specific primers.
The granulocytic antigens NA1 and NA2 are two allelic gene products of the FcgammaRIIIB gene. These antigens are frequently targets of granulocytic-specific allo-antibodies and auto-antibodies that cause neutropenias. Different distributions of these antigens have been found in population studies. In our study, the genomic DNA of 345 healthy, unrelated Spanish individuals was typed for NA1 and NA2 using polymerase chain reaction (PCR) with sequence-specific primers (SSP). The gene frequencies found in the Spanish population were 0.29 for NA1 and 0.71 fo NA2. Flow cytometry immunotyping was also carried out in 20 of these samples, and an exact correlation was observed among the results. The gene frequencies determined in our study are similar to those reported in other Caucasian populations. The null phenotype reported in other serological studies was not found. This typing system can be used in population studies instead of serological tests as a more rapid, simple and reproducible method.


Prolactin response to bromperidol treatment in schizophrenic patients.
The prolactin response to an antipsychotic drug, bromperidol was studied in 24 schizophrenic in-patients (13 males. 11 females). Eight patients were given 6 mg/day, 8 were given 18 mg/day. Duration of treatment was 3 weeks. Plasma concentrations of bromperidol and reduced bromperidol were measured by high-performance liquid chromatography, and that of prolactin was measured by radioimmunoassay. Bromperidol treatment significantly (P < 0.01) increased plasma concentration of prolactin each week. The mean +/- S.D. of the delta-prolactin (the mean concentration during treatment minus the pretreatment concentration) was 13.3 +/- 12.4 ng/ml. Multiple regression analysis showed that the delta-prolactin concentration was significantly greater in females than in males (P < 0.05) and correlated to plasma concentrations of bromperidol (P < 0.001) and reduced bromperidol (P < 0.0001). These results suggest that the prolactin response to bromperidol treatment depend on plasma concentrations of both bromperidol and reduced bromperidol and gender, and that reduced bromperidol is involved in the pharmacological effects during bromperidol treatment.


Mild-temperature photothermal assisted CuSi nanowires for promoting infected wound healing.
In clinical practice, the utilization of antibiotics is still the main approach for the treatment of wound contamination, which lacks the ability to accelerate wound healing and arises the global concern of antimicrobial resistance. Plenty of alternative methods have been explored in recent years due to the fast development of material science. Here, CuO/SiO2 nanowires (CuSi NWs) with good near-infrared (NIR) photothermal conversion ability are synthesized by a one-step hydrothermal method. The as-prepared CuSi NWs possess excellent antibacterial ability against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which could be enhanced by the assistance of mild photothermal therapy (PTT). Moreover, CuSi NWs at suitable concentrations can promote proliferation, migration, and angiogenic gene expression of human umbilical vein endothelial cells (HUVECs), exhibiting a remarkable pro-vascularization ability. The in vivo mouse infect model further proves that the CuSi NWs might be a good candidate for the treatment of infected wounds as the high antibacterial efficiency and accelerated wound healing is obtained.


Social support and well-being in adolescents: the mediating role of hopefulness.
The purpose of this study was to examine the extent to which hopefulness mediates the relationship between perceived social support and general well-being in midadolescents. The sample consisted of 99 high school students, aged 15 to 17, all of whom completed the Personal Resource Questionnaire (PRQ85-Part II), a social support measure, the Hopefulness Scale for Adolescents, and the Adolescent General Well-Being Questionnaire in classroom settings. Statistically significant positive correlations were found between perceived social support and general well-being, perceived social support and hopefulness, and hopefulness and general well-being. Hopefulness was a potent mediator in the relationship between perceived social support and general well-being in midadolescents.


Color purity in polymer electrochromic window devices on indium-tin oxide and single-walled carbon nanotube electrodes.
Dual polymer absorptive/transmissive electrochromic (EC) window devices have been assembled using the solution-processable and high-EC-contrast polymer PProDOT-(CH(2)OEtHx)(2) as the EC material, along with a non-color-changing electroactive polymer, poly(2,2,6,6-tetramethylpiperidinyloxy-4-yl methacrylate) (PTMA), as the counter electrode material. Indium-tin oxide (ITO) and highly transmissive single-walled carbon nanotube (SWNT) film coated glass electrodes are used as electrode substrates. The use of the EC/non-color-changing polymer combination allowed us to construct window devices that rapidly switch between magenta and highly transmissive (>95% T for ITO and approximately 79% T for SWNT) states with large optical modulation (>71% DeltaT for ITO and 66% DeltaT for SWNT). The devices showed effective coloration and bleaching: the lightness parameter (L*) changing from 67 to 95 for ITO (approximately 50-92 for SWNT), essentially reaching a diffuse white upon oxidation. The color modulates from highly pure magenta with a* = 28 (red hue) and b* = -28 (blue chroma) for ITO (a* = 40 and b* = -36 for SWNT) to nearly colorless with a* = 1 and b* = -1 for ITO (a* = -2 and b* = -3 for SWNT) devices. Increasing the switching voltage from 2.55 V up to 3.5 V resulted in faster SWNT-based window device performance.


Avian models to study the transcriptional control of hematopoietic lineage commitment and to identify lineage-specific genes.
E26 is an avian acute leukemia virus with a profound ability to transform multipotent hematopoietic progenitor cells both in vivo and in vitro. Progenitor cells transformed by this virus can be expanded in vitro as undifferentiated clones for up to two months and can also be induced to differentiate into cells of the erythroid, eosinophilic, thrombocytic, and myelomonocytic lineages with reproducible kinetics. Aside from the proliferative stimulus provided by the E26 oncoprotein, these cells are remarkably similar to normal hematopoietic progenitors. They therefore provide an ideal assay system for determining the influence of ectopically expressed transcription factors on both maturation and commitment to several hematopoietic lineages. Results from experiments using this system suggest that subtle shifts in the balance of lineage-restricted transcription factors can result in profound changes in phenotype and challenge the notion that lineage commitment is a uni-directional process. Analysis of the regulatory elements governing the expression of these genes has provided novel mechanistic insights into the transcriptional control of hematopoiesis. In addition to their utility in deciphering the control of lineage commitment, the ability to grow large numbers of undifferentiated and more mature hematopoietic cells has facilitated the discovery of a number of novel, lineage-restricted genes. Analysis of the proteins encoded by these genes is helping to clarify the role of a number of membrane proteins in the interaction between hematopoietic cells and their microenvironments.


[Rich selenium-Banqiao-Codonopsis Pilosula mixture enhances immune function of aging mice].
To investigate the effect of rich selenium-Banqiao-Codonopsis Pilosula (RSBCP) mixture on the immune functions of the aging mice. Sixty Kunming mice (half male and half female) were randomly divided into high-, middle- and low-dose RSBCP mixture groups, model group and control group, with twelve mice in each group. The control group was injected intraperitoneally with 500 mg/(kg.d) normal saline and the other groups were injected with the same amount of D-galactose. The RSBCP mixture high-, middle- and low-dose groups were respectively gavaged with 100, 50, 25 g/(kg.d) RSBCP mixture at the moment when D-galactose was injected. The model group and control group were given the same amount of distilled water instead. The mice were killed at the 30th days and the indexes of thymus and spleen were measured. The serum levels of IgG, IgM, C3, C4, interleukine 2 (IL-2), IL-6 and tumor necrosis factor alpha (TNF-α) were detected by ELISA and the major T-cell subsets of splenocytes were analyzed by flow cytometry. Compared with the control group, the indexes of thymus and spleen in the model group decreased obviously; the serum levels of IgG, IgM, C3, C4, IL-2 and IL-6 were reduced significantly and the level of TNF-α increased significantly. Compared with the model group, the indexes of thymus and spleen in the RSBCP mixture groups increased obviously; the levels of IgG, IgM, C3, C4, IL-2 and IL-6 were raised significantly and the level of TNF-α decreased significantly. Compared with the control group, the indexes of thymus and spleen in the RSBCP mixture high-dose group increased obviously; the levels of IgG, IgM, C3, C4, IL-2 and IL-6 were lifted significantly and the level of TNF-α decreased significantly. The indexes of thymus and spleen and the levels of IgG, IgM, C3, C4, IL-2 and IL-6 in the RSBCP mixture middle- and low-dose groups had no obvious differences from those of the control group. Compared with the control group, the model group showed significantly decreased numbers of CD3⁺ T, CD4⁺ T, CD44⁺ T cells and significantly increased number of CD8⁺ T cells. Compared with the model group, the RSBCP mixture groups showed significantly increased numbers of CD3⁺ T, CD4⁺ T, both the high- and middle-dose groups showed significantly increased numbers of CD44⁺ T cells and significantly decreased number of CD8⁺ T cells. RSBCP mixture could delay the atrophy of thymus and spleen in the aging mice, dramatically elevate serum levels of IgG, IgM, C3, C4, IL-2, IL-6, lower the level of TNF-α, and influence the proportions of T cell subsets. The mixture plays a role in enhancing the immune function of aging mice.


Joint Effects of Peer Presence and Fatigue on Risk and Reward Processing in Late Adolescence.
Peers are thought to increase adolescents' risk-taking behavior, at least in part, by heightening their sensitivity to rewards. In this study, we investigate whether the effect of peers on late adolescent males is exacerbated when youth are cognitively fatigued, a state characterized by weakened cognitive control and heightened orientation toward rewards, and well established as a factor that compromises decision making. We hypothesized that fatigued adolescents' top-down regulation of reward-related impulses may be compromised, thereby potentially amplifying the effect of peers on reward- and risk-seeking behavior. Late adolescent males between 18 and 22 years old (mean age = 19.64, SD = 1.22; 61% Caucasian) completed a decision-making battery either alone or in the presence of 3 same-sex peers, and were either cognitively fatigued or non-fatigued. We compared behavior between four experimental groups-fatigued adolescents in a peer group, non-fatigued adolescents in a peer group, fatigued adolescents by themselves, and non-fatigued adolescents by themselves. The findings showed that cognitive fatigue and peer presence evinced independent effects on risk taking and sensitivity to rewards, but that these factors do not influence adolescent decision-making in an additive or synergistic fashion. To our surprise, being fatigued reduces (but does not eliminate) the effect of peers of risk taking. Moreover, the impact of peers on adolescent males' ability to learn from negative consequences is not compromised when adolescents are in a state of mental fatigue. Our results suggest that mental fatigue increases late adolescent males' reward sensitivity to the same extent as peer presence, but does not amplify the peer effect on risk-taking behavior. In this regard, grouping adolescents when they are fatigued may be less dangerous than when they are rested. Similarly, the added presence of peers does not further exacerbate the effect of fatigue on adolescent's reward- and risk-seeking inclinations. In fact, given peers' unique effect on adolescents' ability to learn from costly decisions, our findings suggest that seeking the presence of peers-which is often a rewarding experience in and of itself-may be an adaptive response to mitigate the impact of fatigue on decision making.


Progress toward poliomyelitis eradication--African Region, 1997.
In 1988, the World Health Assembly established the goal of eradicating poliomyelitis worldwide by 2000. To achieve this goal, the World Health Organization (WHO) promotes the implementation of specific strategies. Eradicating polio from the African continent is one of the remaining major challenges to achieving global eradication by the target date. This report summarizes progress in the African Region of WHO in 1997 with the implementation of polio eradication strategies, and suggests that polio eradication by 2000 remains a feasible target.