Parkinson's-adapted cognitive stimulation therapy: feasibility and acceptability in Lewy body spectrum disorders.
Drug-based therapeutic approaches for Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are moderately effective and not always tolerated. Tailoring psychosocial approaches in PDD and DLB may offer additional support and improve outcomes. We adapted home-based, care partner-delivered Cognitive Stimulation Therapy (CST) for individuals with PDD or DLB and their care partners (CST-PD). To evaluate the feasibility, acceptability, and tolerability of CST-PD. This randomised controlled trial used mixed methods, including a process evaluation. People with PDD, DLB or mild cognitive impairment in PD (PD-MCI) and their care partners were randomised to 12 weeks of treatment as usual (TAU) or CST-PD. Outcomes were feasibility of the study conduct (i.e., recruitment, retention rate) and acceptability and tolerability of the intervention. Measures included rating scales, researcher field notes, therapy diaries, and exploratory clinical and care partner efficacy measures. The recruitment target was met with 76 consenting participant-dyads. Retention in both arms was high at over 70%. More than 90% of dyads undertook discrete sessions greater than 20 min duration, but the average number of sessions completed was lower than the recommended dose. Acceptability ratings (i.e., interest, motivation and sense of achievement) of the intervention were high. Participants reported no serious adverse events related to the intervention. The field of psychosocial interventions for PDD and DLB is newly emerging, and we demonstrated that this type of intervention is acceptable and well tolerated. Evaluating its clinical effectiveness in a full-scale randomized controlled clinical trial is warranted. The trial is a psychosocial intervention with an allocated ISRCTN number 11455062.


The emergency bed service in London--who uses it?
As part of wider review, this study examines the pattern of referrals to the emergency bed service from seven selected health districts in London over a six-month period. A 12-fold variation in the use of the emergency bed service was found between the different districts. Half the referrals to the service were made by doctors working in deputizing services, less than 1% of referrals were due to inter-hospital transfers and half the referrals were made by general practitioners. A few general practitioners were high users: 46% of the general practitioner referrals were accounted for by only 5% of the practitioners.The second part of the study concerned a questionnaire survey of a sample of general practitioners in the seven health districts (n = 963) and an 83% response rate was achieved. Almost three-quarters of the respondents did not use the emergency bed service. Wide variation between the different health districts was again demonstrated. In spite of the variations described, the survey revealed a continuing demand for the service by general practitioners.


The effect of Ultraviolet-B irradiation on the photodegradation of ciprofloxacin and norfloxacin as inhibitors of bacterial DNA replication and cell division in urea medium.
Ciprofloxacin hydrochloride and Norfloxacin are second-generation fluoroquinolone antibiotic against bacterial DNA gyrase, which reduces DNA strain throughout replication. As DNA gyrase is essential through DNA replication, subsequent DNA synthesis and cell division are inhibited. Direct photolysis of fluoroquinolones was studied by using UV irradiation in the presence or absence of other substances that generate free radicals. This study aimed to assess the effect of Ultraviolet B (UVB) irradiation in removing ciprofloxacin and norfloxacin by using a simulating model of wastewater contained urea at pH 4. A known concentration of ciprofloxacin and norfloxacin were prepared in an appropriate aqueous solution in presence or absence 0.2M urea and adjusted at pH 4. The dis-solved drugs were irradiated with UVB-lamp in a dark place for 60 minutes. The percent of removal and the rate of elimination (k) of each drug were calculated. The direct photolysis effect of UVB irradiation was observed with ciprofloxacin which amounted to 24.4% removal compared with12.4% removal of norfloxacin after 60 minutes of irradiation. The effect of UVB irradiation was enhanced by urea to reach 38.9% and 15% for ciprofloxacin and norfloxacin. The calculated k of ciprofloxacin has amounted to three folds of that of norfloxacin. Direct photolysis of ciprofloxacin and norfloxacin can be achieved simply by using a simulation model of 0.2 M urea and UVB irradiation at pH 4. UVB is highly effective in removing ciprofloxacin compared with norfloxacin by 2-3 folds.


Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial.
Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1-17 years were enrolled in three age cohorts (12-17 years, 4-11 years, and 1-3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1-3 years after placebo injection to 21% (30 of 144) of children aged 4-11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12-17 years and 4-11 years age cohorts after the first and second dose, and pyrexia in the 1-3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12-17 years (9929 ELISA units [EU]/mL [95% CI 8172-12 064]), in 119 (99%) of 120 aged 4-11 years (10 212 EU/mL [8419-12 388]), and in 118 (98%) of 121 aged 1-3 years (22 568 EU/mL [18 426-27 642]). The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1-17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.


An examination of the differences between two methods of estimating energy expenditure in resistance training activities.
To date, few studies have looked at the energy expenditure (EE) of individual resistance training (RT) exercises. The purpose of this study was to evaluate the EE of 4 modes of RT (push-ups, curl-ups, pull-ups, and lunges) using 2 different calculation methods for estimating EE. Twelve healthy men with a minimum of 1 year of RT experience were randomly assigned to an RT circuit. Each circuit contained the 4 RT exercises in a specified order. The participants completed 3 trials of their assigned circuit during one visit to the laboratory. Oxygen consumption was measured continuously throughout the trial using indirect calorimetry. Two different calculation methods were applied to estimate EE. Using the traditional method (TEC), we estimated EE by calculating the average oxygen consumption recorded during each activity. Using the second, nontraditional method (NEC), we estimated EE by calculating the average oxygen consumption recorded during the recovery period. Independent T-tests were used to evaluate mean EE differences between the 2 methods. Estimates of EE obtained from the NEC were significantly higher for all the 4 activities (p < 0.001). Using the NEC, 3 of the 4 activities were classified as vigorous intensity (push-ups: 6.91 metabolic equivalents (METs); lunges: 7.52 METs; and pull-ups: 8.03 METs), whereas none were classified as vigorous using the TEC. Findings suggest that the methods we use to calculate the EE of anaerobic activities significantly affect EE estimates. Using the TEC may underestimate actual EE of anaerobic activities.


Rhegmatogenous retinal detachment complicating diabetic retinopathy.
Retinal detachment complicating proliferative diabetic retinopathy is being recognized with increasing frequency. Although one type of detachment is tractional and requires vitrectomy for hopeful repair, the other variety of detachment is rhegmatogenous. The rhegmatogenous form of retinal detachment does not generally require the radical surgical approach of vitrectomy. However, because of the unusual nature of the retinal detachment , a standard encircling scleral buckling procedure does not suffice to correct the problem. The unusual characteristics of this form of retinal detachment are discussed, and the criteria for types of surgical repair are considered. A modification of scleral buckling procedure which has been successful in anatomically reattaching most rhegmatogenous retinal detachments is described. The complications resulting from surgery are reviewed along with methods to avoid complications.


End-user searching in medicine.
Investigation of end-user searching at the New York Hospital-Cornell University Medical Center (NYH-CUMC) revealed that 8% of the physicians surveyed were end users, 63% were interested in learning to search, and 29% were not interested. When training sessions were offered at the Burke Rehabilitation Center, an affiliated institution, 50% of the medical staff attended at least one class, but only 7% of the total staff became frequent searchers. Analysis of the precision and recall ratios of searches conducted by five end users at HYH-CUMC indicated that the best results were obtained by end users who had been taught to search by experienced librarian-searchers. The quality of end user searches did not appear to be affected by the "friendliness" of the systems used, the frequency of searching habits, or the length of time that an end user had been searching.


Candidate genes for shell colour polymorphism in Cepaea nemoralis.
The characteristic ground colour and banding patterns on shells of the land snail Cepaea nemoralis form a classic study system for genetics and adaptation as it varies widely between individuals. We use RNAseq analysis to identify candidate genes underlying this polymorphism. We sequenced cDNA from the foot and the mantle (the shell-producing tissue) of four individuals of two phenotypes and produced a de novo transcriptome of 147,397 contigs. Differential expression analysis identified a set of 1,961 transcripts that were upregulated in mantle tissue. Sequence variant analysis resulted in a set of 2,592 transcripts with single nucleotide polymorphisms (SNPs) that differed consistently between the phenotypes. Inspection of the overlap between the differential expression analysis and SNP analysis yielded a set of 197 candidate transcripts, of which 38 were annotated. Four of these transcripts are thought to be involved in production of the shell's nacreous layer. Comparison with morph-associated Restriction-site Associated DNA (RAD)-tags from a published study yielded eight transcripts that were annotated as metallothionein, a protein that is thought to inhibit the production of melanin in melanocytes. These results thus provide an excellent starting point for the elucidation of the genetic regulation of the Cepaea nemoralis shell colour polymorphism.


Electro-optic modulator with exceptional power-size performance enabled by transparent conducting electrodes.
An EO phase modulator having transparent conducting oxide electrodes and an inverted rib waveguide structure is demonstrated. This new modulator geometry employs an EO polymer having an in-device r33 = 60pm/V. The measured half-wave voltage Vpi of these devices ranges from 5.3V to 11.2V for 3.8 and 1.5 mm long devices, respectively. The lowest VpiL figure-of-merit corresponds to 0.6V-cm (7.2mW-cm(2) of power length product) in a dual-drive configuration. The trade-off between Vpi, insertion loss and modulation bandwidth is systematically analyzed. An optimized high-speed structure is proposed, with numerical simulation showing that this new structure and an in-device r33 = 150pm/V, can achieve Vpi = 0.5V in a 5mm long active length with dual drive operation. The insertion loss is targeted at 6dB, and a 3dB optical modulation bandwidth can reach > 40GHz.


Regulation of SR-BI-mediated high-density lipoprotein metabolism by the tissue-specific adaptor protein PDZK1.
A novel mechanism for the regulation of lipoprotein receptor activity is providing new insights into the control of lipid metabolism. The tissue-specific adaptors ARH (autosomal recessive hypercholesterolemia) and PDZK1 [where PDZ derives from postsynaptic density protein (PSD-95)/Drosophila discs-large (dlg)/tight-junction protein (ZO1)] have been shown to control the activities of distinct types of lipoprotein receptors in a posttranscriptional fashion, significantly affecting overall lipoprotein metabolism. This review will focus on one of these lipoprotein receptor-adaptor pairs, the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and its adaptor PDZK1. The PDZ domain-containing adaptor protein PDZK1 has been shown to bind to and control the activity of the high-density lipoprotein receptor SR-BI via a tissue-specific posttranscriptional mechanism. Mice deficient in PDZK1 have elevated plasma cholesterol levels due to the virtually complete hepatic ablation of SR-BI, implicating PDZK1 as a novel regulator of high-density lipoprotein metabolism. The functions of ARH and PDZK1 suggest that other adaptor proteins may be found to control the activities of other cell-surface receptors in a similar tissue-specific fashion. Manipulation of the expression and/or activities of such adaptors might provide new insights into receptor physiology and these adaptors may prove to be attractive targets for pharmaceutical intervention in cholesterol metabolism-related disease processes.


Ferrodispersion: a promising candidate for an optical capacitor.
A ferrodispersion, which comprises micrometer-sized magnetizable spheres dispersed in a ferrofluid, is shown to store retrievable optical energy. It is observed that when such dispersion is subjected to a transverse magnetic field and a linearly polarized monochromatic light with its electric vector perpendicular to the applied field is incident on it, then for a critical static magnetic field of moderate intensity the emerging light disappears. Upon removing the light and then switching off the field, again light of the same frequency and same state of polarization reappears. A time delay between emission of the light and switching off the field is observed. The statistical distribution of this delay is reported. Intensity of the retrieval signal is found to depend on the storage time. This effect is investigated. Storing and retrieval of optical energy will be useful for developing a magnetically tunable optical capacitor.


Unidirectional Influx and Net Accumulation of PIB.
The compound {N-methyl-[(11)C]}2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, "PIB", measured by positron emission tomography, has been demonstrated to image brain beta-amyloid deposition in Alzheimer's disease (AD). In the present study the benefit of measuring the PIB accumulation rate together with the unidirectional influx of PIB into the brain was investigated in healthy control subjects and patients with AD. In a monkey changes in the influx rate constant K(1) of PIB closely followed changes in CBF, caused by alteration of Pa(CO2). In addition, K(1) was high both in the monkey and in humans, suggesting that this parameter reflects CBF. Most AD patients studied showed clearly higher accumulation rate for PIB than the controls in cortical brain areas, while a few patients showed as low accumulation as the controls. K(1) did not correlate with the accumulation rate, indicating that K(1) for PIB provides extra information besides the accumulation rate.


Reducing Caloric Intake Prevents Ischemic Injury and Myocardial Dysfunction and Affects Anesthetic Cardioprotection in Type 2 Diabetic Rats.
Background. Type 2 diabetes mellitus (T2DM) increases the risk of myocardial ischemia, followed by increased perioperative risk of cardiovascular morbidity. We investigated whether reducing caloric intake reduces ischemic injury and myocardial dysfunction and affects the protective effects of the volatile anesthetic sevoflurane in diet-induced T2DM rats. Methods. Rats received a western (WD) or control diet (CD). Caloric intake was reduced by reversing WD-fed rats to CD. Myocardial function was determined with echocardiography. After 8 weeks of diet feeding, myocardial infarction was induced and the effect of sevoflurane was studied on myocardial function and ischemia/reperfusion injury. Results. WD-feeding resulted in a mild T2DM phenotype and myocardial dysfunction. Sevoflurane further impaired systolic function in WD-fed rats. Unexpectedly, WD-feeding reduced infarct size compared to CD-feeding. Sevoflurane reduced infarct size in CD-fed rats; however it enlarged infarct size in WD-fed rats. Caloric reduction restored myocardial dysfunction and the protective effect of sevoflurane against ischemia compared to WD-fed rats, whereas the protective effects of WD-feeding persisted. Conclusion. Caloric reduction restored the T2DM phenotype and myocardial function, while the cardioprotective properties of WD-feeding or sevoflurane persisted. Our data suggest that reducing caloric intake in T2DM might be a possible intervention to reduce perioperative risk of cardiovascular morbidity.


The impact of ejaculatory dysfunction upon the sufferer and his partner.
Ejaculatory function cannot be evaluated outside the dyadic process and without taking into account the men's and women's cognition of the condition and how their subjective perception impacts on the evaluation of the relationship and sexual quality. Although the distress of the sufferer and his partner has been a motivating factor in leading men with ejaculatory dysfunction to seek medical help, few objective or prospective evaluations of the effects on the couple have been reported. Specialized literature has been dealing with ejaculatory disorders in a heterogeneous manner. Comparatively, there are far more studies on premature ejaculation (PE) than on delayed ejaculation (DE) and even fewer studies on other male orgasm disorders. Therefore, the review focuses on the literature of the two most studied ejaculatory disorders. The matter presented in this article can also be considered for other ejaculatory disorders, since all of them relate to a failure of control, changing the intravaginal ejaculatory latency time (IELT), with consequences for men and their partners. There are multiple psychological explanations as to why a man develops PE or DE. Unfortunately, none of the theories evolve from evidence-based studies. The common final pathway of these factors is the irrational fear of ejaculating intravaginally. These sexual disorders may also cause personal distress for the sexual partner and decreased sexual satisfaction for the couple. An association between pre-existing anxiety disorders and sexual performance anxiety has been found in men and couples with ejaculatory dysfunction. This could reflect a process in which pre-existing anxiety triggers sexual dysfunction, causing performance anxiety and leading to a vicious cycle: anxiety, sexual dysfunction, more anxiety. Men with DE are similar to men with other sexual dysfunctions. They show the same elevated level of sexual dissatisfaction and they also show lower levels of coital frequency. To a lower extent, they use more masturbatory activity relative to controls. The burden of PE for the patient is revealed in three different levels: the emotional burden, the health burden, and the burden on the relationship. In terms of the emotional burden, there is often a sense of embarrassment and shame at not being able to satisfy their partner, and patients often have low self-esteem, feelings of inferiority, anxiety, anger, and disappointment. Men feel frustrated about their PE and how it affects their intimacy with their partners and the sexual relationship. In conclusion, ejaculatory dysfunction has a negative impact on both the man and his female partner and, consequently, it has implications for the couple as a whole. Additionally, ejaculatory dysfunction extending beyond a year elevates the risk of depression in these patients. Although partner perceptions of PE generally indicated less dysfunction than those of subjects, partner outcomes measures play a part in the assessment of PE. Ejaculatory dysfunction involves the integration of physiological, psychobehavioral, cultural, and relationship dimensions. All these elements need to be considered in the treatment.


Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB.
The aim of the present study was to investigate the effect and molecular mechanism of tanshinone IIA (TSA) on colon cancer cells. Cell viability was determined using Cell Counting kit-8 assay and the results demonstrated that TSA treatment significantly decreased the cell viability of HCT1116 and COLO205 cells in a dose-dependent manner. TSA treatment also sensitized HCT1116 and COLO205 cells to fluorouracil therapy in a concentration-dependent manner. Western blotting was performed in order to investigate the molecular mechanisms of TSA action and determine the level of phosporylated p65 and nuclear factor-κB (NF-κB)-regulated genes, including vascular endothelial growth factor (VEGF), c-Myc, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2). The results revealed that TSA treatment greatly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TSA treatment. TSA also decreased the expression levels of VEGF, c-Myc, COX-2 and Bcl-2. Furthermore, the inhibition of NF-κB activation with the specific inhibitor, pyrrolidine dithiocarbamate, increased the induction of cell death and chemosensitization effect of TSA in colon cancer cells. In conclusion, these results suggest that TSA induces cell death and chemosensitizes colon cancer cells through the suppression of NF-κB signaling.


A demonstration of a multi-method variable selection approach for treatment selection: Recommending cognitive-behavioral versus psychodynamic therapy for mild to moderate adult depression.
Objective: We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method: Data are drawn from a randomized comparison of CBT versus PDT for depression (N = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual's optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results: Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d = 0.37). Conclusions: Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used.


Environmental, life-style, and physical precursors of clinical Parkinson's disease: recent findings from the Honolulu-Asia Aging Study.
Increased westernization with Japanese migration to the U. S. in the early 20(th) century is thought to have altered the risk of cardiovascular disease. Whether similar effects include changes in the risk of Parkinson's disease (PD) is not clear. This report describes the relations between environmental, life-style, and physical attributes and the incidence of PD that have been observed in the Honolulu-Asia Aging Study. Beginning in 1965, environmental, life-style, and physical attributes were recorded at selected examinations in a cohort of 8,006 Japanese-American men. Subjects were followed for clinical PD. During 30 years of follow- up, PD was observed in 137 men. Overall incidence (7.1/10,000 person-years) was generally higher than in Asia and similar to rates observed in Europe and the U. S. Precursors of PD included constipation, adiposity, years worked on a sugar or pineapple plantation, years of exposure to pesticides, and exposure to sugar cane processing. Factors showing an inverse association with PD included coffee intake and cigarette smoking. Among dietary factors, carbohydrates increased the risk of PD while the intake of polyunsaturated fats appeared protective. Total caloric intake, saturated and monounsaturated fats, protein, niacin, riboflavin, beta-carotene, vitamins A, B, and C, dietary cholesterol, cobalamin, alpha-tocopherol, and pantothenic acid showed no clear relation with clinical PD. Findings suggest that several environmental, life-style, and physical attributes appear to be precursors of PD. Whether patterns of precursors can be used to identify individuals at high risk of future PD or can broaden the scope of early interventions or recruitment into neuroprotective trials warrants further study.


Infrared microscopy for the study of biological cell monolayers. I. Spectral effects of acetone and formalin fixation.
Infrared spectroscopy of biological cell monolayers grown on surfaces is a poorly developed field. This is unfortunate because these monolayers have potential as biological sensors. Here we have used infrared microscopy, in both transmission and transflection geometries, to study air-dried Vero cell monolayers. Using both methods allows one to distinguish sampling artefactual features from real sample spectral features. In transflection experiments, amide I/II absorption bands down-shift 9/4 cm(-1), respectively, relative to the corresponding bands in transmission experiments. In all other spectral regions no pronounced frequency differences in spectral bands in transmission and transflection experiments were observed. Transmission and transflection infrared microscopy were used to obtain infrared spectra for unfixed and acetone- or formalin-fixed Vero cell monolayers. Formalin-fixed monolayers display spectra that are very similar to that obtained using unfixed cells. However, acetone fixation leads to considerable spectral modifications. For unfixed and formalin-fixed monolayers, a distinct band is observed at 1740 cm(-1). This band is absent in spectra obtained using acetone-fixed monolayers. The 1740 cm(-1) band is associated with cellular ester lipids. In support of this hypothesis, two bands at 2925 and 2854 cm(-1) are also found to disappear upon acetone fixation. These bands are associated with C-H modes of the cellular lipids. Acetone fixation also leads to modification of protein amide I and II absorption bands. This may be expected as acetone causes coagulation of soluble cellular proteins. Other spectral changes associated with acetone or formalin fixation in the 1400-800 cm(-1) region are discussed.


Ca(V)1.2 and Ca(V)1.3 L-type calcium channels regulate the resting membrane potential but not the expression of calcium transporters in differentiated PC12 cells.
PC12 cells differentiated under the influence of the neuronal growth factor (NGF) serve as a model of both sympathetic neurons and chromaffin cells. NGF-induced differentiation critically depends on elevated intracellular calcium concentration. Main pathway for Ca²⁺ entry in excitable cells is represented by voltage-dependent calcium channels including L-type calcium channels (LTCC). We investigated role of Ca(V)1.2 and Ca(V)1.3 LTCC subtypes in NGF-differentiated PC12 cells. The expression of LTCC subtypes was downregulated by transfection of NGF-differentiated PC12 cells with siRNA for either CACNA1C or CACNA1D gene. Efficiency of gene silencing was verified by RT-PCR and by functional essay. The dominant LTCC subtype in PC12 cells was Ca(V)1.2. Downregulation of either LTCC significantly hyperpolarized the resting membrane potential. Expression of mRNA for intracellular calcium transporters inositol trisphosphate receptor type 1, 2 and 3, ryanodine receptor type 1 and 2 and sarco/endoplasmic reticulum Ca²⁺ ATPase type 2 as well as plasma membrane transporters Na⁺-Ca²⁺ exchanger type 1 and 2 was not altered in the absence of either LTCC subtype. In conclusion, Ca²⁺ influx through Ca(V)1.2 or to Ca(V)1.3 channel subtypes contributes to maintenance of the resting membrane potentials of NGF-differentiated PC12 cells but is not required for regulation of expression of genes for calcium-transporting proteins.


The influences of muscle fibre proportions and areas upon EMG during maximal dynamic knee extensions.
This study is an investigation of the relationship between muscle morphology and surface electromyographic (EMG) parameters [mean frequency of the power spectrum (MNF), signal amplitude (root mean square, RMS) and the signal amplitude ratio (SAR; i.e. the ratio between the RMS level during the passive part of the contraction cycle and the RMS level during the active part of the contraction cycle)] during 100 maximal dynamic knee extensions at 90 degrees. s(-1). Each contraction cycle comprised of 1 s of active knee extension and 1 s of passive knee flexion. The surface EMG was recorded from the vastus lateralis muscle. Twenty clinically healthy subjects participated in the study, and muscle biopsy samples of the vastus lateralis were obtained from 19 of those subjects. The relationships between muscle morphology and EMG were investigated at three stages of the test: initially, during the fatigue phase (initial 40 contractions), and at the endurance level (the final 50 contractions). Major findings on correlations are that SAR and MNF tended to correlate positively with the proportion of type 1 fibres, and RMS correlated positively with the proportion of type 2 muscle fibres. The muscle fibre areas showed little correlation with the EMG variables under investigation. The results of the present study showed that the three EMG variables of a dynamic endurance test that were investigated (RMS, MNF and SAR) were clearly correlated with the proportions of the different fibre types, but only to a small extent with fibre areas. These findings contradict some of the theoretical models of the EMG, especially for parameters in the frequency domain.


High-dose prenalterol in beta-blockade intoxication.
This study presents a case of beta-blocker intoxication due to massive overdose of metoprolol (7.5 g). Prenalterol in a dose of 420 mg was given as antidote, in combination with epinephrine in intermittent doses. Resuscitation was performed during 4 hours because of mechanical asystole. The patient regained health in 24 hours after further repeated doses of 30 mg prenalterol. Prenalterol is valuable in the management of toxic doses of beta-blocking drugs, and a titration to extremely high doses of prenalterol might be necessary.


Calcitonin gene-related peptide enhances experimental autoimmune encephalomyelitis by promoting Th17-cell functions.
T(h)17 cells, an inflammatory T helper cell subset, are involved in the pathogenesis of various inflammatory, autoimmune and allergic diseases. Recent evidence supports the idea that immune cell functions and the inflammatory response are finely regulated by various physiological substances. Calcitonin gene-related peptide (CGRP), a neuropeptide released from the sensory nerve endings, is one of these mediators. By binding to its receptor composed of receptor activity-modifying protein 1 (RAMP1) and calcitonin receptor-like receptor, CGRP modulates various immune cell functions, but the function of CGRP in T(h)17 cells is largely unknown. Here, we investigated the effect of CGRP signaling on T(h)17 cells and T(h)17 cell-mediated inflammation and observed that CGRP activates nuclear factor of activated T cells c2 through cAMP/PKA to increase IL-17 production in vitro. In vivo, IL-17 production is suppressed in RAMP1-deficient mice in the experimental autoimmune encephalomyelitis (EAE) model and RAMP1-deficient mice are completely resistant to EAE. Furthermore, T(h)17 cell function and EAE induction are also suppressed in T cell-specific RAMP1-deficient mice. Taken together, our findings indicate that CGRP promotes T(h)17 cell-mediated autoimmune inflammation through the regulation of IL-17 expression.


PlantPAD: a platform for large-scale image phenomics analysis of disease in plant science.
Plant disease, a huge burden, can cause yield loss of up to 100% and thus reduce food security. Actually, smart diagnosing diseases with plant phenomics is crucial for recovering the most yield loss, which usually requires sufficient image information. Hence, phenomics is being pursued as an independent discipline to enable the development of high-throughput phenotyping for plant disease. However, we often face challenges in sharing large-scale image data due to incompatibilities in formats and descriptions provided by different communities, limiting multidisciplinary research exploration. To this end, we build a Plant Phenomics Analysis of Disease (PlantPAD) platform with large-scale information on disease. Our platform contains 421 314 images, 63 crops and 310 diseases. Compared to other databases, PlantPAD has extensive, well-annotated image data and in-depth disease information, and offers pre-trained deep-learning models for accurate plant disease diagnosis. PlantPAD supports various valuable applications across multiple disciplines, including intelligent disease diagnosis, disease education and efficient disease detection and control. Through three applications of PlantPAD, we show the easy-to-use and convenient functions. PlantPAD is mainly oriented towards biologists, computer scientists, plant pathologists, farm managers and pesticide scientists, which may easily explore multidisciplinary research to fight against plant diseases. PlantPAD is freely available at http://plantpad.samlab.cn.


A comparative study of sequence- and structure-based features of small RNAs and other RNAs of bacteria.
Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs. We observed that sRNAs differed significantly from the rest with respect to G+C composition, normalized minimum free energy of folding, motif frequency and several RNA-folding parameters like base-pairing propensity, Shannon entropy and base-pair distance. Based on the selected features, we developed a predictive model using Random Forests (RF) method to classify the above four classes of RNAs. Our model displayed an overall predictive accuracy of 89.5%. These findings would help to differentiate bacterial sRNAs from other RNAs and further promote prediction of novel sRNAs in different bacterial species.


Efficacy of ciprofloxacin in animal models of infection.
The antibacterial efficacy of some of the newer quinolone antimicrobial agents in general, and ciprofloxacin in particular, in animal models of experimental septic arthritis, burn wound sepsis, empyema, chronic gastroenteritis, granuloma pouch infection, intraabdominal abscess, osteomyelitis, prostatis, sinusitis, urinary tract infection, and severe septicemia caused by Pseudomonas aeruginosa is reviewed. In addition, the efficacy of these newer quinolones has been studied in animal models of pneumonia, endocarditis, meningitis, skin and soft tissue infections, and a variety of other systemic infections. Although certain limitations are associated with animal models of infection, properly performed studies clearly have the potential to provide guidelines for evaluating the efficacy of antimicrobial agents in the treatment of some infections in humans.


Impact and implementation of simulation-based training for safety.
Patient safety is an issue of imminent concern in the high-risk field of medicine, and systematic changes that alter the way medical professionals approach patient care are needed. Simulation-based training (SBT) is an exemplary solution for addressing the dynamic medical environment of today. Grounded in methodologies developed by the aviation industry, SBT exceeds traditional didactic and apprenticeship models in terms of speed of learning, amount of information retained, and capability for deliberate practice. SBT remains an option in many medical schools and continuing medical education curriculums (CMEs), though its use in training has been shown to improve clinical practice. Future simulation-based anesthesiology training research needs to develop methods for measuring both the degree to which training translates into increased practitioner competency and the effect of training on safety improvements for patients.


Muscle fiber characteristics in postmenopausal women with normal or impaired glucose tolerance.
Muscle fiber characteristics are altered in type 2 diabetes. We studied whether these alterations also exist in impaired glucose tolerance (IGT) and whether they are determinants of insulin sensitivity and glucose tolerance in postmenopausal women. Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from 77 postmenopausal women aged 57-59 years: 50 women with normal glucose tolerance (NGT) and 27 with IGT. The IGT group had a reduced insulin sensitivity compared with the NGT group (euglycemic-hyperinsulinemic clamp) (P = 0.003). The groups did not differ in muscle fiber composition, as judged by the percentage of type I, IIa, or IIx fibers. In contrast, the IGT group had increased size of the IIa (mean +/-SD 3,776+/-987 vs. 3,078+/-862 microm2, P = 0.002) and IIx fibers (2,730+/-1,037 vs. 2,253+/-672 microm2, P = 0.017). There was a trend for the capillary diffusion areas (the muscle area supplied by each capillary) to be larger in the IGT group for the IIa (1,132+/-286 vs. 1,013+/-240 microm2, P = 0.061) and IIx fibers (1,020+/-246 vs. 906+/-240 microm2, P = 0.058). In the entire group, insulin sensitivity correlated with the size of the type IIa fibers (r = -0.28, P = 0.013), but not with the percentages of muscle fiber types. In a multiple regression, insulin sensitivity was determined by body fat content and HDL cholesterol level, while the size of the IIa fibers was not included in the model. Glucose tolerance was independently predicted by the number of capillaries/type I fiber, as well as by insulin sensitivity and triglyceride levels. We conclude that although muscle fiber composition is not altered, women with IGT have larger type IIa and IIx muscle fibers and a trend for increased capillary diffusion areas for these fibers, compared with women with NGT. In the entire group, insulin sensitivity was determined mainly by body fat content, while muscle fiber capillarization may be of importance for glucose tolerance.


Augmenting Biogas Process Modeling by Resolving Intracellular Metabolic Activity.
The process of anaerobic digestion in which waste biomass is transformed to methane by complex microbial communities has been modeled for more than 16 years by parametric gray box approaches that simplify process biology and do not resolve intracellular microbial activity. Information on such activity, however, has become available in unprecedented detail by recent experimental advances in metatranscriptomics and metaproteomics. The inclusion of such data could lead to more powerful process models of anaerobic digestion that more faithfully represent the activity of microbial communities. We augmented the Anaerobic Digestion Model No. 1 (ADM1) as the standard kinetic model of anaerobic digestion by coupling it to Flux-Balance-Analysis (FBA) models of methanogenic species. Steady-state results of coupled models are comparable to standard ADM1 simulations if the energy demand for non-growth associated maintenance (NGAM) is chosen adequately. When changing a constant feed of maize silage from continuous to pulsed feeding, the final average methane production remains very similar for both standard and coupled models, while both the initial response of the methanogenic population at the onset of pulsed feeding as well as its dynamics between pulses deviates considerably. In contrast to ADM1, the coupled models deliver predictions of up to 1,000s of intracellular metabolic fluxes per species, describing intracellular metabolic pathway activity in much higher detail. Furthermore, yield coefficients which need to be specified in ADM1 are no longer required as they are implicitly encoded in the topology of the species' metabolic network. We show the feasibility of augmenting ADM1, an ordinary differential equation-based model for simulating biogas production, by FBA models implementing individual steps of anaerobic digestion. While cellular maintenance is introduced as a new parameter, the total number of parameters is reduced as yield coefficients no longer need to be specified. The coupled models provide detailed predictions on intracellular activity of microbial species which are compatible with experimental data on enzyme synthesis activity or abundance as obtained by metatranscriptomics or metaproteomics. By providing predictions of intracellular fluxes of individual community members, the presented approach advances the simulation of microbial community driven processes and provides a direct link to validation by state-of-the-art experimental techniques.


Joint shape morphogenesis precedes cavitation of the developing hip joint.
The biology and mechanobiology of joint cavitation have undergone extensive investigation, but we have almost no understanding of the development of joint shape. Joint morphogenesis, the development of shape, has been identified as the 'least understood aspect of joint formation' (2005, Birth Defects Res C Embryo Today 75, 237), despite the clinical relevance of shape morphogenesis to postnatal skeletal malformations such as developmental dysplasia of the hip. In this study, we characterise development of early hip joint shape in the embryonic chick using direct capture 3D imaging. Contrary to formerly held assumptions that cavitation precedes morphogenesis in joint development, we have found that the major anatomical features of the adult hip are present at Hamburger Hamilton (HH)32, a full day prior to cavitation of the joint at HH34. We also reveal that the pelvis undergoes significant changes in orientation with respect to the femur, despite the lack of a joint cavity between the rudiments. Furthermore, we have identified the appearance of the ischium and pubis several developmental stages earlier than was previously reported, illustrating the value and importance of direct capture 3D imaging.


Healthcare-associated Staphylococcus aureus bacteremia and the risk for methicillin resistance: is the Centers for Disease Control and Prevention definition for community-acquired bacteremia still appropriate?
To evaluate a new classification for bloodstream infections that differentiates hospital acquired, healthcare associated, and community acquired in patients with blood cultures positive for Staphylococcus aureus. Prospective, observational study. Three tertiary-care, university-affiliated hospitals in Dublin, Ireland, and Strasbourg, France. Two hundred thirty consecutive patients older than 18 years with blood cultures positive for S. aureus. S. aureus bacteremia (SAB) was defined as hospital acquired if the first positive blood culture was performed more than 48 hours after admission. Other SABs were classified as healthcare associated or community acquired according to the definition proposed by Friedman et al. When available, strains of methicillin-resistant Staphylococcus aureus (MRSA) were analyzed by pulsed-field gel electrophoresis (PFGE). Eighty-two patients were considered as having community-acquired bacteremia according to the Centers for Disease Control and Prevention (CDC) classification. Of these 82 patients, 56% (46) had healthcare-associated SAB. MRSA prevalence was similar in patients with hospital-acquired and healthcare-associated SAB (41% vs 33%; P > .05), but significantly lower in the group with community-acquired SAB (11%; P < .03). PFGE of MRSA strains showed that most community-acquired and healthcare-associated MRSA strains were similar to hospital-acquired MRSA strains. On multivariate analysis, Friedman's classification was more effective than the CDC classification for predicting MRSA. These results support the call for a new classification for community-acquired bacteremia that would account for healthcare received outside the hospital by patients with SAB.


Perceiving visual expansion without optic flow.
When an observer moves forward in the environment, the image on his or her retina expands. The rate of this expansion conveys information about the observer's speed and the time to collision. Psychophysical and physiological studies have provided abundant evidence that these expansionary motions are processed by specialized mechanisms in mammalian visual systems. It is commonly assumed that the rate of expansion is estimated from the divergence of the optic-flow field (the two-dimensional field of local translational velocities). But this rate might also be estimated from changes in the size (or scale) of image features. To determine whether human vision uses such scale-change information, we have synthesized stochastic texture stimuli in which the scale of image elements increases gradually over time, while the optic-flow pattern is random. Here we show, using these stimuli, that observers can estimate expansion rates from scale-change information alone, and that pure scale changes can produce motion after-effects. These two findings suggest that the visual system contains mechanisms that are explicitly sensitive to changes in scale.


Malignant non-urothelial neoplasms of the urinary bladder: a review.
Non-urothelial bladder tumors frequently present a diagnostic and therapeutic challenge. We review the peer-reviewed literature to summarize the available evidence on the etiology, diagnosis and optimal management of malignant non-urothelial bladder tumors. A comprehensive MEDLINE database search was performed. In addition, the proceedings of recent national and international urological and cancer society meetings were reviewed. Primary non-urothelial bladder tumors are rare in Europe and North America representing less than 5% of all bladder lesions combined. A large number of risk factors have been implicated in the etiology of non-schistosomiasis-related squamous cell carcinoma, yet their exact pathomechanism remains poorly defined. Squamous cell carcinoma, adenocarcinoma, small cell carcinoma, sarcoma and carcinosarcoma/sarcomatoid tumors share an unfavorable prognosis despite aggressive surgical management that relates both to an aggressive biological behaviour as well as to an often times advanced stage at the time of diagnosis. Inflammatory pseudotumors are benign tumors of uncertain histogenesis that may mimic sarcomas. Paraganglioma, primary melanoma and lymphoma represent additional, exceedingly rare bladder tumors. The systematic investigation of most non-urothelial bladder tumors is limited by the rarity of these lesions. A concerted effort of multiple institutions linked together in a national or international tumor registry will be necessary to advance our understanding of these tumors, evaluate treatment strategies and optimize patient outcome in the future.


The role of elective lymph node dissection in the management of patients with thick cutaneous melanoma.
A retrospective search of patients seen at the Duke Melanoma Clinic from 1970 to 1986 identified 308 clinically Stage I patients, with 4.0 to 10.0 mm cutaneous melanomas. Five-year and ten-year survival was 56% and 43%, respectively. Elective lymph node dissection (ELND) was done in 116 patients (37.7%); there was no difference in disease-free interval (DFI) or survival between these patients versus patients treated with wide excision only (P = 0.9). Thirty-two patients (27.6%) had pathologically positive nodes on ELND. These patients had a shorter DFI (P = 0.05) and survival (P = 0.03) compared with patients with negative node dissections. When further divided by Breslow's thickness, this difference persisted in patients with 4.0 to 6.0 mm lesions (P = 0.01). However, for thicker lesions (greater than 6.0 mm), there was no difference in survival between the node-negative and node-positive groups (P = 0.9). The mean follow-up was 7.1 years. Elective lymph node dissection was not done in 192 patients; 78 of these recurred first in the regional nodes. These 78 patients were compared with the 32 patients who had pathologically positive nodes by ELND to see if patient survival was improved by early removal of nodal disease. There was no difference in DFI (P = 0.5) or survival (P = 0.3) between these two groups. It is concluded that ELND may provide prognostic information for patients with thick cutaneous melanomas. However, there was no change in DFI or ultimate survival when patients were followed, and nodes removed when clinically positive. The authors do not recommend ELND for patients with thick melanomas because the risk of distant metastases outweighs any benefit of regional node dissection.


Genome-Wide Survey of Invertase Encoding Genes and Functional Characterization of an Extracellular Fungal Pathogen-Responsive Invertase in Glycine max.
Invertases are essential enzymes that irreversibly catalyze the cleavage of sucrose into glucose and fructose. Cell wall invertase (CWI) and vacuolar invertase (VI) are glycosylated proteins and exert fundamental roles in plant growth as well as in response to environmental cues. As yet, comprehensive insight into invertase encoding genes are lacking in Glycine max. In the present study, the systematic survey of gene structures, coding regions, regulatory elements, conserved motifs, and phylogenies resulted in the identification of thirty⁻two putative invertase genes in soybean genome. Concomitantly, impacts on gene expression, enzyme activities, proteins, and soluble sugar accumulation were explored in specific tissues upon stress perturbation. In combination with the observation of subcellular compartmentation of the fluorescent fusion protein that indeed exported to apoplast, heterologous expression, and purification in using Pichia pastoris system revealed that GmCWI4 was a typical extracellular invertase. We postulated that GmCWI4 may play regulatory roles and be involved in pathogenic fungi defense. The experimental evaluation of physiological significance via phenotypic analysis of mutants under stress exposure has been initiated. Moreover, our paper provides theoretical basis for elucidating molecular mechanisms of invertase in association with inhibitors underlying the stress regime, and will contribute to the improvement of plant performance to a diverse range of stressors.


Enhancing electronic and optoelectronic performances of tungsten diselenide by plasma treatment.
Transition metal dichalcogenides (TMDCs) have recently become spotlighted as nanomaterials for future electronic and optoelectronic devices. In this work, we develop an effective approach to enhance the electronic and optoelectronic performances of WSe2-based devices by N2O plasma treatment. The hole mobility and sheet density increase by 2 and 5 orders of magnitude, reaching 110 cm2 V-1 s-1 and 2.2 × 1012 cm-2, respectively, after the treatment. At the same time, the contact resistance (Rc) between WSe2 and its metal electrode drop by 5 orders of magnitude from 1.0 GΩ μm to 28.4 kΩ μm. The WSe2 photoconductor exhibits superior performance with high responsivity (1.5 × 105 A W-1), short response time (<2 ms), high detectivity (3.6 × 1013 Jones) and very large photoconductive gain (>106). We have also built a lateral p-n junction on a single piece of WSe2 flake by selective plasma exposure. The junction reaches an exceedingly high rectifying ratio of 106, an excellent photoresponsivity of 2.49 A W-1 and a fast response of 8 ms. The enhanced optoelectronic performance is attributed to band-engineering through the N2O plasma treatment, which can potentially serve as an effective and versatile approach for device engineering and optimization in a wide range of electronic and optoelectronic devices based on 2D materials.


National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report.
Subsequent neoplasms (SN) after hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplantation lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to affect risk, including patient-related (eg, age), primary disease-related (eg, disease type, pre-HCT therapies), and HCT-related characteristics (eg, type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era because of substantial advances in clinical transplantation practices. Additionally, the influence of nontransplantation-related risk factors (eg, germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventive, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventive, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists to reduce the burden of SN in the rapidly growing population of HCT survivors.


Systemic 5-fluorouracil producing an inflammatory response in porokeratosis.
Topical 5-fluorouracil has been used as an effective treatment for porokeratosis. Upon its treatment, an inflammatory effect occurs with the topical 5-fluorouracil. We report a case of a patient with disseminated superficial actinic porokeratosis displaying a comparable inflammatory process following therapy with systemic 5-fluorouracil used to manage a metastatic breast cancer.


Genetic algorithm-based neural fuzzy decision tree for mixed scheduling in ATM networks.
Future broadband integrated services networks based on asynchronous transfer mode (ATM) technology are expected to support multiple types of multimedia information with diverse statistical characteristics and quality of service (QoS) requirements. To meet these requirements, efficient scheduling methods are important for traffic control in ATM networks. Among general scheduling schemes, the rate monotonic algorithm is simple enough to be used in high-speed networks, but does not attain the high system utilization of the deadline driven algorithm. However, the deadline driven scheme is computationally complex and hard to implement in hardware. The mixed scheduling algorithm is a combination of the rate monotonic algorithm and the deadline driven algorithm; thus it can provide most of the benefits of these two algorithms. In this paper, we use the mixed scheduling algorithm to achieve high system utilization under the hardware constraint. Because there is no analytic method for schedulability testing of mixed scheduling, we propose a genetic algorithm-based neural fuzzy decision tree (GANFDT) to realize it in a real-time environment. The GANFDT combines a GA and a neural fuzzy network into a binary classification tree. This approach also exploits the power of the classification tree. Simulation results show that the GANFDT provides an efficient way of carrying out mixed scheduling in ATM networks.


Carbohydrate metabolism during vertebrate appendage regeneration: what is its role? How is it regulated?: A postulation that regenerating vertebrate appendages facilitate glycolytic and pentose phosphate pathways to fuel macromolecule biosynthesis.
We recently examined gene expression during Xenopus tadpole tail appendage regeneration and found that carbohydrate regulatory genes were dramatically altered during the regeneration process. In this essay, we speculate that these changes in gene expression play an essential role during regeneration by stimulating the anabolic pathways required for the reconstruction of a new appendage. We hypothesize that during regeneration, cells use leptin, slc2a3, proinsulin, g6pd, hif1α expression, receptor tyrosine kinase (RTK) signaling, and the production of reactive oxygen species (ROS) to promote glucose entry into glycolysis and the pentose phosphate pathway (PPP), thus stimulating macromolecular biosynthesis. We suggest that this metabolic shift is integral to the appendage regeneration program and that the Xenopus model is a powerful experimental system to further explore this phenomenon. Also watch the Video Abstract.


Endocytosis in guinea pig seminal vesicle epithelial cells cultivated in chemically defined medium.
We have developed a chemically defined monolayer culture system for guinea pig seminal vesicle epithelial cells (SVEP). The cells appeared as a polarized monolayer with apical microvilli, tight junctions and desmosome-like junctions, and often dilated intercellular spaces. SVEP expressed epithelial-specific cytokeratins as detected immunocytochemically. Growth was obtained during the first week of culture. In this period, the cells were exposed to unconjugated horseradish peroxidase (HRP), a ricin-peroxidase conjugate (Ri-HRP), or cationized ferritin (CF). HRP was endocytosed without binding to the SVEP surface (fluid-phase endocytosis) and was found mainly in multivesicular endosomes and lysosomes. Ri-HRP and CF, however, were endocytosed following binding to the cell surface. Initially these markers were present in multivesicular endosomes, but later also in smaller tubular and vesicular endosomes, some Golgi-associated elements (but not Golgi stacks), and lysosomes. We conclude that our SVEP culture system may be useful in further studies, on e.g. hormonal regulation of endocytosis and other processes of importance for SVEP maintenance and modulation of the seminal fluid in vivo.


Glycemic response to carbohydrate and the effects of exercise and protein.
The purpose of this study was to investigate the effects of pre-exercise and protein coingestion on the glycemic response to carbohydrates. Twenty-one volunteers (13 males and 8 females) aged 22 y (± 3.8 y) participated in four trials in random order. These included: 1) glucose ingestion at rest (RG), 2) glucose and protein ingestion at rest (RGP), 3) glucose ingestion after exercise (EG), and 4) glucose and protein ingestion after exercise (EGP). Exercise consisted of 45 min of cycling at 60% of participants' age-predicted maximum heart rate. Test drinks contained 50 g glucose or 50 g glucose with 20 g whey protein. Venous blood samples were taken at baseline and subsequently every 15 min for 2 h after drink consumption. Blood plasma was subsequently analyzed for glucose and insulin. Plasma glucose concentration was significantly lower in the RGP group than in the RG group at 30, 45, 60, and 75 min and in the EGP group than in the EG group at 30, 45, and 60 min (P < 0.05). Plasma insulin area under the curve was significantly higher in the RGP group than in the RG group and in than in the EGP group than in the EG group (P < 0.05). No significant effect of exercise was seen on glycemic or insulinemic responses. Coingestion of protein with carbohydrate reduces glycemic response and increases insulinemic response in healthy subjects, whereas pre-exercise seems to have no effect.


Munchausen's syndrome in neurosurgery: report of two cases and review of the literature.
Munchausen's syndrome is a rare psychiatric condition, in which patients seek medical treatment for factitious or self-induced medical problems. Reports in the literature of postoperative Munchausen's syndrome are extremely rare. The major obstacle to improving management of the patients with Munchausen's syndrome is increasing physicians' awareness and recognition of the disease. Although Munchausen's syndrome is rare, physicians probably will encounter at least one such patient at some point during their career and therefore should be aware of this disorder. We report two documented cases of postoperative Munchausen's syndrome in patients who underwent cranial neurosurgery. Both patients received complex flaps for closure of their cranial defects. Both patients later admitted to deliberately reopening their cranial wounds because of a psychological desire to continue their illness. The primary therapeutic objective is to achieve wound healing and stop the cycle of surgical procedures. Immediate confrontation with the patient often does more harm than good. Instead, psychiatric consultation, with the potential for nonsurgical management and behavior modification, should be obtained. Munchausen's syndrome is a rare psychiatric diagnosis, especially in the postoperative patient. The common clues to diagnosis are: 1) a nonhealing wound in the absence of risk factors for wound failure, 2) a history of psychiatric illness, 3) repeated bleeding from the wound site, and 4) a desire to continue the sick role. Early detection will allow proper psychiatric referral to prevent injuries to the patient, abuses to the medical system, and unnecessary operations.


Novel Homozygous Missense Variant in GJA3 Connexin Domain Causing Congenital Nuclear and Cortical Cataracts.
Congenital cataracts (CC) are responsible for approximately one-tenth of childhood blindness cases globally. Here, we report an African American family with a recessively inherited form of CC. The proband demonstrated decreased visual acuity and bilateral cataracts, with nuclear and cortical cataracts in the right and left eye, respectively. Exome sequencing revealed a novel homozygous variant (c.563A > G; p.(Asn188Ser)) in GJA3, which was predicted to be pathogenic by structural analysis. Dominantly inherited variants in GJA3 are known to cause numerous types of cataracts in various populations. Our study represents the second case of recessive GJA3 allele, and the first report in African Americans. These results validate GJA3 as a bona fide gene for recessively inherited CC in humans.


Distinct Opsin 3 (Opn3) Expression in the Developing Nervous System during Mammalian Embryogenesis.
Opsin 3 (Opn3) is highly expressed in the adult brain, however, information for spatial and temporal expression patterns during embryogenesis is significantly lacking. Here, an Opn3-eGFP reporter mouse line was used to monitor cell body expression and axonal projections during embryonic and early postnatal to adult stages. By applying 2D and 3D fluorescence imaging techniques, we have identified the onset of Opn3 expression, which predominantly occurred during embryonic stages, in various structures during brain/head development. In addition, this study defines over twenty Opn3-eGFP-positive neural structures never reported before. Opn3-eGFP was first observed at E9.5 in neural regions, including the ganglia that will ultimately form the trigeminal, facial and vestibulocochlear cranial nerves (CNs). As development proceeds, expanded Opn3-eGFP expression coincided with the formation and maturation of critical components of the central and peripheral nervous systems (CNS, PNS), including various motor-sensory tracts, such as the dorsal column-medial lemniscus (DCML) sensory tract, and olfactory, acoustic, and optic tracts. The widespread, yet distinct, detection of Opn3-eGFP already at early embryonic stages suggests that Opn3 might play important functional roles in the developing brain and spinal cord to regulate multiple motor and sensory circuitry systems, including proprioception, nociception, ocular movement, and olfaction, as well as memory, mood, and emotion. This study presents a crucial blueprint from which to investigate autonomic and cognitive opsin-dependent neural development and resultant behaviors under physiological and pathophysiological conditions.


Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes.
The expression of serologic HLA-B27 epitopes on leukocytes of patients with reactive arthritis or ankylosing spondylitis has been shown to be modified in the course of the disease. The purpose of this work was to study whether phagocytosis of arthritis-triggering microbes in vitro alters the expression of HLA-B27 molecules on human antigen-presenting cells and to characterize the underlying mechanisms. Human monocytes and HLA-B27- or HLA-A2-transfected human U-937 cells were exposed to Yersinia enterocolitica serotype O:3. The expression of different epitopes of HLA-B27 was monitored by using immunofluorescence, and their synthesis was determined by quantitative immunoprecipitation. Our results show that phagocytosis of Y. enterocolitica serotype O:3 changed the expression of serological HLA-B27 epitopes. This was due to the reduced synthesis of HLA-B27 molecules. The expression of especially the epitopes which depend on the presence of peptides in the antigen-binding groove was changed. The expression of the ME1 epitope, which has been shown to be important for T-cell recognition in patients with reactive arthritis, was decreased. Down-regulation of epitopes important for the T-cell recognition may impair the elimination of arthritis-triggering microbes and lead to persistent infection. In addition, Y. enterocolitica serotype O:3 seemed to alter the repertoire of peptides presented by the HLA-B27 molecules on human monocytes. This may have a role in the pathogenesis of reactive arthritis via an autoimmune mechanism.


Prognostic value of spleen tyrosine kinase in human solid tumors.
Spleen tyrosine kinase (SYK) was reported to be dysregulated in solid tumors and played an important role in cancer progression. However, the clinical and prognostic values of SYK in solid tumors remain unclear. This meta-analysis investigated the association between SYK expression and clinical outcomes in the patients with solid tumors. A comprehensive literature search was conducted by screening the online electronic databases of PubMed, Embase, and the China National Knowledge Infrastructure. The hazard ratio (HR) with its corresponding 95% CI was used to explore the prognostic value of SYK. We analyzed a total of 1,075 patients from 10 studies, which met the criteria for this meta-analysis. Our pooled results demonstrated that a low expression of SYK did not correlate significantly with shorter overall survival (OS; HR=0.64, 95% CI: 0.34-1.21, P=0.169) or poorer disease-free survival (HR=0.51, 95% CI: 0.13-2.02, P=0.338). However, in a subgroup analysis based on tumor type and test method, under-expression of SYK was positively associated with worse OS in the groups of breast cancer (BC; HR=0.51, 95% CI: 0.32-0.80, P=0.003), hepatocellular carcinoma (HCC; HR=0.44, 95% CI: 0.29-0.69, P<0.001), methylation (HR=0.39, 95% CI: 0.30-0.51, P<0.001), and quantitative reverse transcription polymerase chain reaction (HR=0.24, 95% CI: 0.09-0.65, P=0.005). This meta-analysis demonstrated that under-expression of SYK may serve as a predictive biomarker for poor prognosis in BC and HCC patients. In other solid tumors, the clinical usefulness should be confirmed by large-scale studies.


Genetic analysis of organ fusion in Arabidopsis thaliana.
Postgenital organ fusion occurs most commonly during reproductive development and is important in many angiosperms during genesis of the carpel. Although a number of mutants have been described that manifest ectopic organ fusion, little is known about the genes involved in regulating this process. In this article we describe the characterization of a collection of 29 Arabidopsis mutants showing an organ fusion phenotype. Mapping and complementation analyses revealed that the mutant alleles define nine different loci distributed throughout the Arabidopsis genome. Multiple alleles were isolated for the four complementation groups showing the strongest organ fusion phenotype while the remaining five complementation groups, all of which show only weak floral organ fusion, have a single representative allele. In addition to fusion events between aerial parts of the shoot, some mutants also show abnormal ovule morphology with adjacent ovules joined together at maturity. Many of the fusion mutants isolated have detectable differences in the rate at which chlorophyll can be extracted; however, in one case no difference could be detected between mutant and wild-type plants. In three mutant lines pollen remained unresponsive to contact with the mutant epidermis, demonstrating that organ fusion and pollen growth responses can be genetically separated from one another.


The impact of general self-efficacy and the severity of malocclusion on acceptance of removable orthodontic appliances in 10- to 12-year-old patients.
The patients' acceptance of a treatment plan and their subsequent cooperation play a crucial role in achieving the best results in orthodontic treatments. Evidences show some personality traits such as general self-efficacy (GSE) and some dental traits such as severity of malocclusion are correlated with motivation of orthodontic treatment. These factors may predict the patients' compliance and acceptance in using removable orthodontic appliances. This cross sectional study was conducted to assess the correlation of GSE and the severity of malocclusion with patients' acceptance in using removable orthodontic appliances. This study recruited 50 patients aged 10-12 years who required removable orthodontic appliances. The severity of malocclusion was determined using the index of orthodontic treatment need (IOTN) before the onset of treatment and GSE of participants were assessed using GSE scale self-report. The acceptance questionnaire was proposed to the patients on first (T1), third (T2), and sixth (T3) month after the delivery of the appliance. The GSE score had a statistically significant correlation with the total score of the acceptance questionnaire, subscale score of satisfaction with the appliance during eating and oral hygiene practice, duration of usage of the appliance, and interest in using it (P < 0.05). The IOTN had no significant correlation with the acceptance questionnaire. Our findings substantiate the role of the GSES, concurrently declining the role of the IOTN in prediction of 10-12-year-old children's acceptance and cooperation in treatment of malocclusion with removable appliances.


An integrated metabolomics approach for the research of new cerebrospinal fluid biomarkers of multiple sclerosis.
Multiple Sclerosis (MuS) is a disease caused due to an autoimmune attack against myelin components in which non proteic mediators may play a role. Recent research in metabolomics and lipidomics has been driven by rapid advances in technologies such as mass spectrometry and computational methods. They can be used to study multifactorial disorders like MuS, highlighting the effects of disease on metabolic profiling, regardless of the multiple trigger factors. We coupled MALDI-TOF-MS untargeted lipidomics and targeted LC-MS/MS analysis of acylcarnitines and aminoacids to compare cerebrospinal fluid metabolites in 13 MuS subjects and in 12 patients with Other Neurological Diseases (OND). After data processing and statistical evaluation, we found 10 metabolites that significantly (p < 0.05) segregate the two clinical groups. The most relevant result was the alteration of phospholipids levels in MuS and the correlation between some of them with clinical data. In particular lysophosphatidylcholines (m/z = 522.3 Da, 524.3 Da) and an unidentified peak at m/z = 523.0 Da correlated to the Link index, lysophosphatidylinositol (m/z = 573.3 Da) correlated to EDSS and phosphatidylinositol (m/z = 969.6 Da) correlated to disease duration. We also found high levels of glutamate in MuS. In conclusion, our integrated mass spectrometry approach showed high potentiality to find metabolic alteration in cerebrospinal fluid. These data, if confirmed in a wider clinical study, could open the door for the discovery of novel candidate biomarkers of MuS.


Longnon-coding RNA BLACAT2 promotes gastric cancer progression via the miR-193b-5p/METTL3 pathway.
Gastric cancer is one of the leading prevalent and malignant cancers worldwide, especially in east Asia. However, the in-depth molecular mechanism underlying gastric cancer progression remains uncertain. Recently, studies have identified that long non-coding RNA (lncRNA) could play critical roles in the tumorigenesis of multiple types of cancer. Studies on long non-coding RNA BLACAT2 have proven that it participates in bladder cancer and colorectal cancer regulation and was identified as highly expressed using the cBioPortal for Cancer Genomics in gastric cancer. However, the precise function of lncRNA-BLACAT2 in the carcinogenesis and progression of gastric cancer remains largely unexplored. Our study discovered that lncRNA-BLACAT2 was significantly upregulated in gastric cancer. Different studies have illustrated that BLACAT2 promoted gastric cancer progression through regulating proliferation, migration, invasion, and apoptosis in terms of biological function. Furthermore, BLACAT2 was verified to perform its function through interaction with miR-193b-5p using a luciferase reporter assay. On the other hand, MiR-193b-5p specific inhibitor treatment reversed the inhibitory effect of BLACAT2 on cell biological functions. Additional studies also discovered that Methyltransferase Like 3 (METTL3) was the downstream target of miR-193b-5p. Subsequently, restoration of METTL3 eliminated the suppressive effect of proliferation or the promotive effect of apoptosis caused by BLACAT2 knockdown. To sum up, these experimental results demonstrated that BLACAT2 acted as an oncogene in gastric cancer progression through the regulation of the miR-193b-5p/METTL3 pathway, hence providing new insights regarding the pathogenesis of gastric cancer.


Tuberculosis of the hip. Treatment with closed irrigation and suction using streptomycin.
In 51 children with tuberculosis of the hip, overall end results were better, and the range of motion was improved when irrigation-suction with Streptomycin was included in the regimen of surgical management.


Dual properties of pharmacological activities and preparation excipient: Bletilla striata polysaccharides.
Bletilla striata has been used for thousands of years and shows the functions of stopping bleeding, reducing swelling, and promoting healing in traditional applications. For Bletilla striata, Bletilla striata polysaccharides (BSP) is the main active ingredient, exhibiting biological functions of anti-inflammatory, anti-oxidant, anti-fibrotic, immune modulation, anti-glycation, and so on. In addition, BSP has exhibited the characteristics of excipient such as bio-adhesion, bio-degradability, and bio-safety and has been prepared into a series of preparations such as nanoparticles, microspheres, microneedles, hydrogels, etc. BSP, as both a drug and an excipient, has already aroused more and more attention. In this review, publications in recent years related to the extraction and identification, biological activities, and excipient application of BSP are reviewed. Specifically, we focused on the advances in the application of BSP as a formulation excipient. We hold opinion that BSP not only needed more researches in the mechanisms, but also the development into hydrogels, nano-formulations, tissue engineering, and so on. And we believe that this paper provides a beneficial reference for further BSP innovation and in-depth research and promotes the use of these natural products in pharmaceutical applications.


Assessment of SPM in perfusion brain SPECT studies. A numerical simulation study using bootstrap resampling methods.
Statistical parametric mapping (SPM) has become the technique of choice to statistically evaluate positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) functional brain studies. Nevertheless, only a few methodological studies have been carried out to assess the performance of SPM in SPECT. The aim of this paper was to study the performance of SPM in detecting changes in regional cerebral blood flow (rCBF) in hypo- and hyperperfused areas in brain SPECT studies. The paper seeks to determine the relationship between the group size and the rCBF changes, and the influence of the correction for degradations. The assessment was carried out using simulated brain SPECT studies. Projections were obtained with Monte Carlo techniques, and a fan-beam collimator was considered in the simulation process. Reconstruction was performed by using the ordered subsets expectation maximization (OSEM) algorithm with and without compensation for attenuation, scattering, and spatial variant collimator response. Significance probability maps were obtained with SPM2 by using a one-tailed two-sample t-test. A bootstrap resampling approach was used to determine the sample size for SPM to detect the between-group differences. Our findings show that the correction for degradations results in a diminution of the sample size, which is more significant for small regions and low-activation factors. Differences in sample size were found between hypo- and hyperperfusion. These differences were larger for small regions and low-activation factors, and when no corrections were included in the reconstruction algorithm.


The Impact of Evidence-Based Practices on Postoperative Pain in Patients undergoing Gastrointestinal Surgery in Amiralmomenin Hospital in Zabol During 2014-2015.
The Evidence-Based Practices (EBP), have gained considerable ground in treatment and care, increases the quality of nurses' clinical care. Yet EBP is less frequently employed despite its efficiency and importance. Pain management is an important component of nursing care and sufficient pain control has still remained as a challenge despite routine nursing practices that are already provided. The present study intended to define the impact of evidence-based nursing practices on postoperative pain in patients undergoing gastrointestinal surgery. The present study was a single group quasi-experimental study with before/after design. The study was conducted in the General Surgery Departments of the Amiralmomenin Hospital in Zabol during 2014-2015. A purposive sampling method was used to study 55 patients undergoing abdominal surgery. The data collection tool was a questionnaire. The patients pain severity was defined before and after implementing evidence-based practices. The collected data were analysed in SPSS using descriptive statistics and inferential statistics. The results showed that 61.8% of patients experienced severe postoperative pain. The mean perceived pain ratings in women and men were 7.88±1.78 and 9.42±0.81, respectively. The mean pain intensity was 8.48±1.66 before the intervention and reached 7.16±1.71 after the intervention, which was significant based on Kruskal-Wallis test (p=0.003). The mean postoperative pain experienced by the patients (p<0.01) and pain-relief following the intervention (p=0.002) was significant for gender. This study suggests that a high percentage of patients experienced acute postoperative pain despite routine nursing care, while evidence-based nursing practices could significantly alleviate pain.


Associations between hardiness, C-reactive protein, and telomere length among former prisoners of war.
War captivity and posttraumatic stress disorder (PTSD) are known to be associated with several poor health outcomes of an accelerated aging process. However, the contribution of personality protective factors to this phenomenon are rarely studied. The present 24-year prospective study examined associations between psychological hardiness and three health outcomes: C-reactive protein (CRP) levels, metabolic syndrome (MetS), and telomere length (TL). Eighty-eight Israeli former prisoners of war (ex-POWs) were assessed 18 (T1) and 42 (T2) years after repatriation. Data on hardiness was collected at T1 while leukocyte TL, CRP, and MetS data was collected 42 years after the war. While adjusting for age, body mass index (BMI), self-rated health, depressive and PTSD symptoms at T2, higher levels of hardiness at T1 predicted decreased CRP and longer TL at T2. Long-term health vulnerabilities of traumatized ex-POWs are manifested in an accelerated aging process and cellular senescence. Raising awareness of the importance of protective factors such as veterans' hardiness might be associated with improving their longevity and well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Testosterone stimulates angiogenesis and vascular regrowth in the ventral prostate in castrated adult rats.
The castration-induced regression and testosterone stimulated regrowth of the vasculature in the rat ventral prostate lobe were studied using stereological techniques. Seven days after castration, the endothelial cell proliferation rate (bromodeoxyuridine labeling index); the total weights of blood vessel walls, blood vessel lumina, endothelial cells, glandular epithelial cells; and total organ weight were all decreased. Within 2 days after sc treatment with testosterone, the total weights of blood vessel walls, endothelial cells, and vascular lumina, as well as the endothelial cell proliferation rate, were all normalized. In contrast to the rapid response of the vasculature, the total weight of glandular epithelium and total organ weight were not normalized during the 4 days of testosterone treatment. Growth of the vasculature apparently precedes growth of the glandular epithelium. The testosterone- dependent factors stimulating the vasculature are unknown, but factors derived from epithelial cells, mast cells (which accumulate in the prostate during the first day of testosterone treatment), and tissue macrophages could all be involved. Castration-induced regression and testosterone-stimulated regrowth of the prostatic vasculature can be used as an experimental model to study factors regulating angiogenesis and organ growth in the prostate.


Creating a caring community in nursing education.
In response to the call to reclaim caring in nursing, an associate of science in nursing degree program recently incorporated a curriculum that emphasizes the teaching and learning of caring. To accomplish this goal, caring groups composed of nursing faculty and students were established. The caring group experience involved the creation of a safe place in which nursing students and faculty could engage each other in a reciprocal dialogue of sharing and support. This article reports the findings of a qualitative study designed to discover and describe the lived experience of being in a caring group from the perspective of nursing students. Participants reported being more aware of the meaning and importance of caring in their personal and professional lives, being more accepting of others, and valuing caring and self-care more. They also expressed an intention to recreate the caring group experience in future practice settings. Conclusions from this study address the pedagogical measures necessary to sustain care and caring as the essence of nursing.


The effectiveness of thrombolysis with intravenous alteplase for acute ischemic stroke in daily practice.
Thrombolysis with intravenous alteplase has been proven an effective treatment for patients with acute ischemic stroke in randomized clinical trials. In daily practice, the effect of thrombolysis may be less, and complications may occur more often. The aim of this study was to assess effectiveness and safety of thrombolysis in an unselected observational cohort of patients. During a two-year period, all patients over 18 years with acute stroke who were admitted within four-hours from onset of symptoms in 12 centers were registered. We compared outcomes in patients who were treated with alteplase with patients who were not treated with alteplase. The primary outcome was good functional outcome at three-months measured with the modified Rankin Scale ≤2). The safety end point was symptomatic intracranial hemorrhage and mortality. We used a multivariable logistic regression model to adjust for baseline imbalances and multilevel analysis to take into account within center correlations. Overall, 1657 patients with ischemic stroke were admitted within four-hours from onset of symptoms and 696 (42%) were treated with alteplase. Treatment with alteplase was associated with a favorable outcome (adjusted odds ratio 1·3; 95% confidence interval 1·0 to 1·7). After further adjustment for potential clustering effects, the adjusted odds ratio for good outcome was 1·4 (95% confidence interval 1·0 to 1·8). Thirty-six (5%) of the 696 patients treated with alteplase had a symptomatic intracranial bleeding complication. Thrombolysis for ischemic stroke with intravenous alteplase is an effective treatment also in an unselected observational cohort of patients.


Cocaine-induced endocannabinoid signaling mediated by sigma-1 receptors and extracellular vesicle secretion.
Cocaine is an addictive drug that acts in brain reward areas. Recent evidence suggests that cocaine stimulates synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in midbrain, increasing dopamine neuron activity via disinhibition. Although a mechanism for cocaine-stimulated 2-AG synthesis is known, our understanding of 2-AG release is limited. In NG108 cells and mouse midbrain tissue, we find that 2-AG is localized in non-synaptic extracellular vesicles (EVs) that are secreted in the presence of cocaine via interaction with the chaperone protein sigma-1 receptor (Sig-1R). The release of EVs occurs when cocaine causes dissociation of the Sig-1R from ADP-ribosylation factor (ARF6), a G-protein regulating EV trafficking, leading to activation of myosin light chain kinase (MLCK). Blockade of Sig-1R function, or inhibition of ARF6 or MLCK also prevented cocaine-induced EV release and cocaine-stimulated 2-AG-modulation of inhibitory synapses in DA neurons. Our results implicate the Sig-1R-ARF6 complex in control of EV release and demonstrate that cocaine-mediated 2-AG release can occur via EVs.


Quantitative phosphoproteomic analysis of ovine muscle with different postmortem glycolytic rates.
Phosphorylation regulates protein structure, function, cell signaling and enzyme activities within cells. Postmortem changes of muscle to meat are partially determined by the structure, function and enzyme activities of proteins. To further understand the mechanisms regulating postmortem changes, ovine muscles with different glycolytic rates were subjected to quantitative phosphoproteomic analysis. Totally 116 unique phosphopeptides matched to 99 phosphoproteins were detected to be different in abundance among the fast, moderate and slow glycolytic rate muscles. Of which, 24 phosphoproteins clustered into glycolysis and muscle contraction were selected after bioinformatics analysis. Quantitative analysis showed that phosphorylation of pyruvate kinase, phosphoglucomutase 1, enolase and fructose-bisphosphate aldolase was correlated with glycolytic rate early postmortem. In addition, some myofibrillar proteins were detected to be differentially phosphorylated. In summary, this study revealed that protein phosphorylation at early postmortem may indirectly affect the glycolysis pathway through the regulation of proteins involved in glycolysis and muscle contraction.


A military home with a heart.
A classically inspired and iconic building by the Thames in south west London, the Royal Hospital Chelsea is home to the equally iconic Chelsea pensioners--retired ex-military staff who have come to live in this unique retirement community. Now the nursing needs of this special group are being met in a new wing of the site, called the Margaret Thatcher Infirmary.


Multispot laser photocoagulation system using a fiber bundle scanner.
A multispot photocoagulation system equipped with a fiber bundle scanner is developed for the treatment of widely spread port wine stain. The laser transmission system consists of multiple quartz fiber, the input ends of which are aligned and driven by a stepper motor across a high-power argon laser beam. The output ends are arranged in a hexagonal close-packed array from which the diverging laser beam successively irradiates different spots of a lesion without the use of a mechanical scan over the lesion. The output patterns from two bundles of graded-index and step-index fibers are analyzed experimentally.


A Sex-Positive Framework for Research on Adolescent Sexuality.
In this article, I propose a sex-positive framework for research on adolescent sexuality in which I consider consensual sexual activities in adolescence as developmentally normative and potentially healthy. The sex-positive framework is contrasted with the predominant "risk" perspective that presumes that abstinence from sexual activity is the ideal behavioral outcome for teenagers. Evidence from longitudinal and behavioral genetic studies indicates that engaging in sexual intercourse in adolescence does not typically cause worse psychological functioning. The relationship context of sexual experience may be a critical moderator of its psychological impact. Moreover, cross-cultural data on adolescents' contraception usage, unintended pregnancy, and sexually transmitted infections suggest that, despite the unacceptably high rate of negative health consequences among U.S. teenagers, adolescents can have the developmental capacity to regulate the health risks inherent in sexual activity. Understanding adolescent sexuality can be fostered by considering sexual well-being, a multidimensional construct that incorporates an adolescent's sexual self-efficacy, sexual self-esteem, feelings of sexual pleasure and satisfaction, and freedom from pain and negative affect regarding sexuality. New research is necessary to understand the development of adolescent sexual well-being, including its normative age trends, its reciprocal links with sexual behavior, and its impact on psychological and physical health.


Idiopathic subglottic stenosis arises at the epithelial interface of host and pathogen.
Idiopathic subglottic stenosis (iSGS) is a rare fibrotic disease of the proximal airway affecting adult Caucasian women nearly exclusively. Life-threatening ventilatory obstruction occurs secondary to pernicious subglottic mucosal scar. Disease rarity and wide geographic patient distribution has previously limited substantive mechanistic investigation into iSGS pathogenesis. By harnessing pathogenic mucosa from an international iSGS patient cohort and single-cell RNA sequencing, we unbiasedly characterize the cell subsets in the proximal airway scar and detail their molecular phenotypes. Results show that the airway epithelium in iSGS patients is depleted of basal progenitor cells, and the residual epithelial cells acquire a mesenchymal phenotype. Observed displacement of bacteria beneath the lamina propria provides functional support for the molecular evidence of epithelial dysfunction. Matched tissue microbiomes support displacement of the native microbiome into the lamina propria of iSGS patients rather than disrupted bacterial community structure. However, animal models confirm that bacteria are necessary for pathologic proximal airway fibrosis and suggest an equally essential role for host adaptive immunity. Human samples from iSGS airway scar demonstrate adaptive immune activation in response to the proximal airway microbiome of both matched iSGS patients and healthy controls. Clinical outcome data from iSGS patients suggests surgical extirpation of airway scar and reconstitution with unaffected tracheal mucosa halts the progressive fibrosis. Our data support an iSGS disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. These results refine our understanding of iSGS and implicate shared pathogenic mechanisms with distal airway fibrotic diseases.


Energy expenditure during gait in patients with mucopolysaccharidosis.
The aim of this study is to evaluate energy expenditure in gait by mucopolysaccharidosis affected patients by means of a simple and adequate to the clinical environment methodology. A cross-sectional study was carried out comparing energy expenditure during gait in 19 patients suffering from mucopolysaccharidosis (MPS Group) with 19 asymptomatic control individuals (Control Group). Energy expenditure was measured in calories (cal) using a Polar telemetric watch (model FT7) during a 50 meter walk. Variables such as age, weight, height, body mass index (BMI), initial hart rate, final hart rate, and walking time, were recorded. MPS Group showed a mean energy expenditure during gait of 2.84 cal (±1,01), versus 1.42 cal (±0,51), 100% higher than the Control Group; MPS also presented increased initial hart rate (22% higher), final hart rate (13% higher) and walking time (13% higher). Energy expenditure during gait in MPS patients was two times higher than control individuals; the methodology used showed to be a promising alternative, also adequate to the standard clinical environment. Level of Evidence III, Cross-sectional Comparative Study.