Some in vitro and in vivo cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal models.
This study was undertaken to investigate some cardiovascular effects of Hypoxis hemerocallidea Fisch & CA Mey (Hypoxidaceae) corm (African potato) aqueous extract in experimental animal paradigms. The effect of the corm aqueous extract (APE) on myocardial contractile performance was evaluated on guinea-pig isolated atrial muscle strips in vitro; whereas the antihypertensive (hypotensive) effect of the plant extract was examined in hypertensive Dahl salt-sensitive rats in vivo. APE (25-400 mg/ml) produced concentration-dependent, significant (p < 0.05-0.001) negative inotropic and negative chronotropic effects on guinea-pig isolated electrically driven left, and spontaneously beating right atrial muscle preparations, respectively. Moreover, APE reduced or abolished, in a concentrationdependent manner, the positive inotropic and chronotropic responses of guinea-pig isolated atrial muscle strips induced by noradrenaline (NA, 1-100 microM) and calcium (Ca2+, 5-40 mM). The negative inotropic and chronotropic effects of APE on guinea-pig atrial muscle strips were not modified by exogenous administration of atropine (ATR, 7.5 x 10(-7)-2.5 - 10(-6) M) to the bath fluid. APE also significantly reduced (p < 0.05-0.001) or abolished in a concentration-dependent manner, the rhythmic, spontaneous, myogenic contractions of portal veins isolated from rats. Furthermore, APE caused dose-related transient but significant (p < 0.05-0.001) reductions in the systemic arterial blood pressure and heart rates of the hypertensive rats used. Although the exact mechanisms of the cardiodepressant and the transient hypotensive (antihypertensive) actions of APE could not be established in the present study, we exclude the involvement of the cholinergic system; since the extract's cardiovascular effects were resistant to atropine pretreatment. However, the results of this laboratory animal study indicated that APE caused bradycardia and brief hypotension in the mammalian experimental models used. These observations tend to suggest that the herb may be used as a natural supplementary remedy in some cases of cardiac dysfunctions and in essential hypertension. The findings of this experimental animal study lend pharmacological support to the folkloric, anecdotal uses of the African potato in the management and/or control of certain cardiac dysfunctions and essential hypertension in some rural communities of southern Africa.


Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study.
The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.


Suppression of reverberations at fiber tips for optical ultrasound sensing.
Fabry-Perot-based ultrasound sensors at fiber tips have performed high sensitivity and immunity of electromagnetic interference with a relatively compact size. Nevertheless, the reverberation at fiber tips causes a strong noise that degrades the sensing capability. Here we propose a fiber optical-based ultrasound sensor with three design approaches to reduce the reverberation, including designs with an eccentric core, absorptive shield, and arc edge. The effect was experimentally validated with a photoacoustic signal excitation. Compared with bare single-mode fibers in simulation, the low-reverberation design increased the signal-to-noise ratio by 32.1 dB with identical excitation. The experimental results demonstrated the "clean" response with almost invisible reverberations, which was validated by a commercial hydrophone. This research solved the reverberation problems and provided a low-noise design for fiber optic ultrasound sensing.


Expression of transforming growth factor alpha during development.
Transforming growth factors (TGFs) are polypeptides that are produced by transformed and tumour cells, and that can confer phenotypic properties associated with transformation on normal cells in culture. One of these growth-regulating molecules, transforming growth factor alpha (TGF-alpha), is a 50 amino acid polypeptide that is related to epidermal growth factor (EGF) and binds to the EGF receptor. Previous studies have shown that TGF-alpha is expressed during rodent embryogenesis between 7 and 14 days gestation. To investigate the cellular sites of TGF-alpha mRNA expression during development, we have performed Northern analyses and in situ hybridization histochemistry on the conceptus and maternal tissues at various gestational ages. Contrary to previous reports, both Northern analyses and in situ hybridization histochemistry indicate that TGF-alpha mRNA is predominantly expressed in the maternal decidua and not in the embryo. Decidual expression is induced following implantation, peaks at day 8, and declines through day 15 when the decidua is being resorbed. In situ hybridization revealed that expression of TGF-alpha mRNA is highest in the region of decidua adjacent to the embryo and is low or nondetectable in the uterus, placenta, and embryo. In addition, we could not detect TGF-alpha mRNA expression in other maternal tissues, indicating that the induction of TGF-alpha transcripts in the decidua is tissue specific, and not a pleiotropic response to changes in hormonal milieu that occur during pregnancy. The developmentally regulated expression of TGF-alpha mRNA in the decidua, together with the presence of EGF receptors in this tissue, suggests that this peptide may stimulate mitosis and angiogenesis locally by an autocrine mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)


[Changes in the incidence of tuberculosis among residents of the Semipalatinsk region].
The incidence of tuberculosis among the Semipalatinsk Region's residents over 29 years (1971-1990) is analyzed. It increased in all age groups (children, adolescents, and adults) and in urban populations. In the last 10 years, the incidence of tuberculosis also rose and reached the rate among males under 40 years.


Promoting healthy sleep.
What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The article discussed the stages of sleep, the factors that may influence quality of sleep, and the effects of suboptimal sleep on patients and nurses.


Postconcussive Symptoms After Single and Repeated Concussions in 10- to 20-Year-Olds: A Cross-Sectional Study.
The objective was to characterize cognitive deficits and postconcussive symptoms in a pediatric population with no concussion, a single concussion, and ≥2 concussions, using a cross-sectional design. Cognitive function and postconcussive symptoms were assessed in participants (age 10-20) with no concussion (n = 1118), single concussion (n = 368), and repeated (≥2) concussions (n = 252). Analyses were adjusted for age and gender. Individuals with ≥2 concussions exhibited more total postconcussive symptoms; more loss of consciousness, amnesia and confusion; more headaches; and poorer cognitive function compared to no concussion and single concussion. Postconcussive symptoms may play a modulatory role in cognitive dysfunction after repeated concussions as those with loss of consciousness, amnesia, confusion, or headaches exhibited worse verbal memory, visual memory, visual-motor processing, and poorer impulse control compared to those without these symptoms. This analysis demonstrates that repeated concussions is associated with poorer cognitive function and postconcussive symptoms compared to a single concussion.


Full time directional versus user selectable microphone modes in hearing aids.
The purpose of this experiment was to systematically examine hearing aid benefit as measured by speech recognition and self-assessment methods across omnidirectional and directional hearing aid modes. These data were used to compare directional benefit as measured by speech recognition in the laboratory to hearing aid wearer's perceptions of benefit in everyday environments across full-time directional, full-time omnidirectional, and user selectable directional fittings. Identification of possible listening situations that resulted in different self reported hearing aid benefit as a function of microphone type was a secondary objective of this experiment. Fifteen adults with symmetrical, sloping sensorineural hearing loss were fitted bilaterally with in-the-ear (ITE) directional hearing aids. Measures of hearing aid benefit included the Profile of Hearing Aid Benefit (PHAB), the Connected Sentence Test (CST), the Hearing in Noise Test (HINT), and a daily use log. Additionally, two new subscales were developed for administration with the PHAB. These subscales were developed to specifically address situations in which directional hearing aids may provide different degrees of benefit than omnidirectional hearing aids. Participants completed these measures in three conditions: omnidirectional only (O), directional only with low-frequency gain compensation (D), and user-selectable directional/omnidirectional (DO). Results from the speech intelligibility in noise testing indicated significantly more hearing aid benefit in directional modes than omnidirectional. PHAB results indicated more benefit on the background noise subscale (BN) in the DO condition than in the O condition; however, this directional advantage was not present for the D condition. Although the reliability of the newly proposed subscales is as yet unknown, the data were interpreted as revealing a directional advantage in situations where the signal of interest was in front of the participant and a directional disadvantage in situations where the signal of interest was behind the listener or localization was required. Laboratory directional benefit is reflected in self-assessment measures that focus on listening in noise when the sound source of interest is in front of the listener. The use of a directional hearing aid mode; however, may have either a positive, a neutral, or a negative impact on hearing aid benefit measured in noisy situations, depending on the specific listening situation.


Multielemental determination in breast cancerous and non-cancerous biopsies by inductively coupled plasma-mass spectrometry following small volume microwave-assisted digestion.
A microwave-assisted digestion method amenable to analysis of small size biological samples (<30 mg dry mass) has been optimized for determining twelve elements (Ag, As, Cd, Co, Cu, Cr, Mn, Mo, Ni, Pb, Se and Zn) by inductively coupled plasma-mass spectrometry (ICP-MS) in breast cancerous and non-cancerous biopsies. The use of three small volume PTFE closed vials (6-mL capacity) placed inside a conventional microwave vessel allows to drastically diminishing the volume of acid needed for digestion. A Plackett-Burman experimental design was used to evaluate the robustness of the digestion procedure. Effects of nitric acid volume, need for predigestion step, microwave power and digestion time were assessed. No significant effects were found, the digestion method being robust enough to be recommended for a routine practice. The method was successfully validated against CRM BCR 185 (bovine liver), CRM NRCC TORT-2 (lobster hepatopancreas), CRM NRCC DORM-2 (dogfish muscle) and CRM NRCC DOLT-2 (dogfish liver). Procedural detection limits ranged from 0.54 to 40 ng g(-1). Within-batch precision values were less than 3%, whereas between-batch precision values were in the range 2-11%. Forty-seven biopsies from thirty-nine women were analyzed: 20 samples corresponding to mammoplasties from healthy women and 27 samples from patients suffering from cancer pathology, 19 of which corresponded to tumour and 8 to adjacent normal tissue. After applying parametric and non-parametric statistical tests, a significant accumulation of Cu, Mn, Zn and Se in cancerous tissues was demonstrated.


Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2 phase and promotes the G2/M cell cycle transition.
Two controversies have emerged regarding the signaling pathways that regulate Golgi disassembly at the G(2)/M cell cycle transition. The first controversy concerns the role of mitogen-activated protein kinase activator mitogen-activated protein kinase kinase (MEK)1, and the second controversy concerns the participation of Golgi structure in a novel cell cycle "checkpoint." A potential simultaneous resolution is suggested by the hypothesis that MEK1 triggers Golgi unlinking in late G(2) to control G(2)/M kinetics. Here, we show that inhibition of MEK1 by RNA interference or by using the MEK1/2-specific inhibitor U0126 delayed the passage of synchronized HeLa cells into M phase. The MEK1 requirement for normal mitotic entry was abrogated if Golgi proteins were dispersed before M phase by treatment of cells with brefeldin A or if GRASP65, which links Golgi stacks into a ribbon network, was depleted. Imaging revealed that unlinking of the Golgi apparatus begins before M phase, is independent of cyclin-dependent kinase 1 activation, and requires MEK signaling. Furthermore, expression of the GRASP family member GRASP55 after alanine substitution of its MEK1-dependent mitotic phosphorylation sites inhibited both late G(2) Golgi unlinking and the G(2)/M transition. Thus, MEK1 plays an in vivo role in Golgi reorganization, which regulates cell cycle progression.


Prevalence of risk factors for coronary artery disease in the community in eastern Nepal--a pilot study.
Coronary artery disease is a major cause of morbidity and mortality in Nepal, however, there are very few published reports of prevalence of various risk factors for coronary artery disease in the community from Nepal. We evaluated 140 adult subjects by simple randomization from all wards in the community in Dharan, a small city located in the foothills in eastern Nepal. After exclusion of subjects with insufficient data, 119 subjects were included for the final analysis. Age ranged from 35 to 86 (mean 54.1+ 10.5) years and there were 63 males and 56 females. Various parameters which were studied included :history of diabetes mellitus, hypertension, coronary artery disease, smoking, hereditary history, family history, measurement of blood pressure, anthropometric parameters such as body mass index and waist hip ratio and biochemical parameters such as random blood sugar and serum cholesterol. The prevalence of various risk factors for coronary artery disease was found to be: hypertension 42 (35.3%), diabetes mellitus--19 (15.9%), history of current smoking--46 (38.7%), hypercholesterolemia--15 (12.6%), sedentary life style 56 (47.1%), body mass index>25 kg/m2--40 (33.6%) and central obesity 50 (42.1%). Approximately one third of the subjects had more than one risk factor. The study highlights prevalence of various risk factors for coronary artery disease in the community. Since majorly of the risk factors are modifiable, timely intervention can help in reducing morbidity and mortality due to this disease.


Cell-wall defective bacteria and Crohn's disease: studies using athymic nude mice.
Indirect immunofluorescence studies were performed to determine whether the antigenic recognition by Crohn's disease (CD) sera of lymphoid tissue from nude (nu/nu) mice injected with CD filtrate is related to cell wall defective pseudomonas-like bacterial revertant forms (CWD-RF). Antisera raised in rabbits against two CWD-RF isolates from CD tissues did not stain lymphomas or hyperplastic lymph nodes produced by CD filtrates, although these tissues demonstrated positive immunofluorescence with CD sera. Pre-absorption of reactive CD sera with CWD-RF did not block this immunofluorescence. Formalinized suspensions of CWD-RF were injected into 36 nu/nu, 12 nu/+, and 31 conventional mice. Thirty other mice were fed suspensions of bacteria. Several nu/nu injected with CWD-RF developed lymphoma (n = 2) and plasma cell hyperplasia (n = 5), none of which reacted with CD sera. Mice fed bacteria did not show intestinal pathology. These studies demonstrate that CWD-RF are not directly related to lymphomagenesis in nu/nu induced by CD filtrates and that different CD serum antibodies are involved in recognition of CWD-RF and lymphoid tissues from nu/nu previously injected with CD filtrates.


Stabilization of garnet/Li interphase by diluting the electronic conductor.
The high interfacial resistance and lithium (Li) dendrite growth are two major challenges for solid-state Li batteries (SSLBs). The lack of understanding on the correlations between electronic conductivity and Li dendrite formation limits the success of SSLBs. Here, by diluting the electronic conductor from the interphase to bulk Li during annealing of the aluminium nitride (AlN) interlayer, we changed the interphase from mixed ionic/electronic conductive to solely ionic conductive, and from lithiophilic to lithiophobic to fundamentally understand the correlation among electronic conductivity, Li dendrite, and interfacial resistance. During the conversion-alloy reaction between AlN and Li, the lithiophilic and electronic conductive LixAl diffused into Li, forming a compact lithiophobic and ionic conductive Li3N, which achieved an ultrahigh critical current density of 2.6/14.0 mA/cm2 in the time/capacity-constant mode, respectively. The fundamental understanding on the effect of interphase nature on interfacial resistance and Li dendrite suppression will provide guidelines for designing high-performance SSLBs.


Electrophysiologic and antiarrhythmic effects of AZD1305 in canine pulmonary vein sleeves.
The objective of this study was to examine the electrophysiologic and antiarrhythmic effects of the new antiarrhythmic agent tert-butyl (2-[7-[2-(4-cyano-2-fluorophenoxy)ethyl]-9-oxa-3,7-diazabicyclo[3.3.1]non3-yl]ethyl)carbamate (AZD1305) in canine pulmonary vein (PV) sleeve preparations isolated from untreated and long-term amiodarone-treated animals. Ectopic activity arising from PV sleeves plays a prominent role in the development of atrial fibrillation (AF). Delayed afterdepolarizations (DADs) and late phase 3 early afterdepolarizations (EADs), originating from the PV have been proposed as potential triggers in initiation of AF. Action potentials were recorded from canine superfused PV sleeves using standard microelectrode techniques. Acetylcholine (1 microM), isoproterenol (1 microM), or their combination was used to induce EADs, DADs, and triggered activity (TA). The effects of AZD1305 (0.1-10 microM) were evaluated in PV sleeve preparations isolated from untreated and amiodarone-treated (40 mg/kg daily for 6 weeks) dogs. AZD1305 (0.1-10 microM, 30 min) significantly prolonged action potential duration and reduced excitability. Abbreviating basic cycle length from 1000 to 300 ms resulted in a decrease of V(max) from 314 +/- 79 to 251 +/- 55 V/s (Delta = -20%) in control and from 177 +/- 53 to 76.5 +/- 33 V/s (Delta = -57%) after AZD1305 (n = 6, p < 0.05). AZD1305 markedly attenuated or suppressed DADs and DAD-induced TA, but not late phase 3 EADs. AZD1305-induced attenuation of excitability, leading to activation failure at much longer cycle lengths, was much more pronounced in PV from amiodarone-treated dogs. Potent effects of AZD1305 to depress excitability, prolong action potential duration, and suppress DAD-induced triggered activity in canine PV sleeve preparations may be effective in suppressing triggers responsible for the genesis of AF and other atrial arrhythmias.


[Clinical course and treatment of duodenal ulcer in women].
Overall 260 women and 202 men were examined comparatively during duodenal ulcer exacerbation. 53.8% of the women demonstrated an atypical disease course. Fibrogastroscopy is a method of early diagnosis of duodenal ulcer in women. As compared to men, the size and depth of ulcers in women was less. Acid and peptic factor was also less pronounced. The four-week treatment with the use of the diet, antacids, gastrozepine and repair agents brought about ulcer healing in 82% of the women. The single and daily doses of antacids administered to women were 1.5 times less than in men. The use of H2-blockers is indicated in women with a severe course of peptic ulcer. The inclusion of antibacterial agents is indicated if the mucous membrane of the antral part of the stomach demonstrates Campylobacter pylori.


The effect of acute exercise on objectively measured sleep and cognition in older adults.
Exercise can improve cognition in aging, however it is unclear how exercise influences cognition, and sleep may partially explain this association. The current study aimed to investigate whether objectively measured sleep mediates the effect of an acute exercise intervention on cognition in older adults. Participants were 30 cognitively unimpaired, physically active older adults (69.2 ± 4.3 years) with poor sleep (determined via self-report). After a triple baseline cognitive assessment to account for any natural fluctuation in cognitive performance, participants completed either a single bout of 20-minutes of high intensity exercise on a cycle ergometer, or a control condition, in a cross-over trial design. Cognition was measured immediately post-intervention and the following day, and sleep (total sleep time, sleep onset latency, sleep efficiency, % of rapid eye movement sleep, light sleep and deep sleep) was characterized using WatchPAT™ at baseline (5 nights) and measured for one night after both exercise and control conditions. Results showed no effect of the exercise intervention on cognition immediately post-intervention, nor an effect of acute exercise on any sleep variable. There was no mediating effect of sleep on associations between exercise and cognition. However, a change from baseline to post-intervention in light sleep and deep sleep did predict change in episodic memory at the ~24 h post-intervention cognitive assessment, regardless of intervention condition. There was no effect of acute high intensity exercise on sleep or cognition in the current study. However, results suggest that associations between sleep and cognition may exist independently of exercise in our sample. Further research is required, and such studies may aid in informing the most effective lifestyle interventions for cognitive health.


Depression, sleep, and antidepressants.
Sleep disturbances are an integral feature of depressive disorders. Like the disorders themselves, the sleep disturbances associated with depression are heterogeneous, ranging from hypersomnia to marked difficulties maintaining sleep. These difficulties are to some extent age dependent and reflect abnormalities of central nervous system arousal. Moreover, the sleep disturbances associated with depression have both reversible, or state-dependent, and more persistent trait-like characteristics. Polysomnographic recordings can be used to document sleep maintenance difficulties, and they often also reveal reduced slow wave sleep, an early onset of the first episode of rapid eye movement (REM) sleep, and increased phasic REM sleep. A deficit of serotonergic neurotransmission, a relative increase in pontine cholinergic activity, and, perhaps, an excess of noradrenergic and corticotropin-releasing hormone activity have been implicated in the pathogenesis of the sleep disturbances of more severe depressive disorders. Antidepressant medications have class- and compound-specific effects on polysomnographic profiles. Unlike other antidepressants, bupropion may increase or intensify REM sleep. While no single effect of antidepressants on sleep neurophysiology is necessary or sufficient for treatment efficacy, differences in drug effects may provide important clues to selection of specific medications for particular patients.


Insights into the Use of Point-of-Care Ultrasound for Diagnosing Obstructive Sleep Apnea.
Obstructive sleep apnea (OSA) is a sleeping disorder caused by complete or partial disturbance of breathing during the night. Existing screening methods include questionnaire-based evaluations which are time-consuming, vary in specificity, and are not globally adopted. Point-of-care ultrasound (PoCUS), on the other hand, is a painless, inexpensive, portable, and useful tool that has already been introduced for the evaluation of upper airways by anesthetists. PoCUS could also serve as a potential screening tool for the diagnosis of OSA by measuring different airway parameters, including retropalatal pharynx transverse diameter, tongue base thickness, distance between lingual arteries, lateral parapharyngeal wall thickness, palatine tonsil volume, and some non-airway parameters like carotid intima-media thickness, mesenteric fat thickness, and diaphragm characteristics. This study reviewed previously reported studies to highlight the importance of PoCUS as a potential screening tool for OSA.


Enhanced attosecond bursts of relativistic high-order harmonics driven by two-color fields.
We study the generation of attosecond x-ray and ultraviolet pulses from relativistically driven overdense plasma targets with two-color incident light. Particle-in-cell simulations show that significant improvement in pulse intensity and isolation is achievable with appropriate laser and plasma parameters. Conversion of 5% of incident laser energy to its second harmonic can enhance the intensity of generated attosecond pulses by an order of magnitude. This approach allows the generation of higher attosecond pulse intensities with existing experimental laser technology and offers a powerful tool for the analysis of the dynamics of relativistic laser-plasma interaction.


The future of the provision process for mobility assistive technology: a survey of providers.
The purpose of this study was to evaluate the opinions of providers of mobility assistive technologies to help inform a research agenda and set priorities. This survey study was anonymous and gathered opinions of individuals who participate in the process to provide wheelchairs and other assistive technologies to clients. Participants were asked to rank the importance of developing various technologies and rank items against each other in terms of order of importance. Participants were also asked to respond to several open-ended questions or statements. A total of 161 providers from 35 states within the USA consented to participation and completed the survey. This survey revealed themes of advanced wheelchair design, assistive robotics and intelligent systems, human machine interfaces and smart device applications. It also outlined priorities for researchers to provide continuing education to clients and providers. These themes will be used to develop research and development priorities. Implications for Rehabilitation • Research in advanced wheelchair design is needed to facilitate travel and environmental access with wheelchairs and to develop alternative power sources for wheelchairs.• New assistive robotics and intelligent systems are needed to help wheelchairs overcome obstacles or self-adjust, assist wheelchair navigation in the community, assist caregivers and transfers, and aid ambulation.• Innovations in human machine interfaces may help advance the control of mobility devices and robots with the brain, eye movements, facial gesture recognition or other systems.• Development of new smart devices is needed for better control of the environment, monitoring activity and promoting healthy behaviours.


Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right Ventricular Cardiomyopathy: 31 Cases (2001-2013).
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in people and boxer dogs that has recently been described in English bulldogs. The objective of this retrospective study was to describe the clinical characteristics of English bulldogs with presumed ARVC. The medical records were searched for English bulldogs examined between 2001 and 2013 with a clinical diagnosis of ARVC. The average age of the 31 dogs identified was 9.2 ± 1.6 yr (range 7-13 yr). Males were overrepresented by a factor of 2.9 to 1. At initial presentation, 5 dogs had subclinical arrhythmia, 10 dogs had clinical signs attributable to arrhythmia, and 16 dogs had congestive heart failure. Eighteen dogs (58%) had ventricular tachycardia and five (16%) also had supraventricular arrhythmias. Four dogs experienced sudden death, 2 dogs died from congestive heart failure, 11 dogs were euthanized for cardiac causes, and 2 dogs died or were euthanized for noncardiac causes. Kaplan-Meier analysis showed a median survival time of 8.3 mo. This is the first study to describe the clinical characteristics of a population of English bulldogs with presumed ARVC. Further studies are needed to better characterize the clinical features of the disease in this breed.


RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes.
The RUNX1 (AML1) gene is a frequent mutational target in myelodysplastic syndromes and acute myeloid leukemia. Previous studies suggested that RUNX1 mutations may have pathological and prognostic implications. We screened 93 patients with cytogenetically normal acute myeloid leukemia for RUNX1 mutations by capillary sequencing of genomic DNA. Mutation status was then correlated with clinical data and gene expression profiles. We found that 15 out of 93 (16.1%) patients with cytogenetically normal acute myeloid leukemia had RUNX1 mutations. Seventy-three patients were enrolled in the AMLCG-99 trial and carried ten RUNX1 mutations (13.7%). Among these 73 patients RUNX1 mutations were significantly associated with older age, male sex, absence of NPM1 mutations and presence of MLL-partial tandem duplications. Moreover, RUNX1-mutated patients had a lower complete remission rate (30% versus 73% P=0.01), lower relapse-free survival rate (3-year relapse-free survival 0% versus 30.4%; P=0.002) and lower overall survival rate (3-year overall survival 0% versus 34.4%; P<0.001) than patients with wild-type RUNX1. RUNX1 mutations remained associated with shorter overall survival in a multivariate model including age and the European Leukemia Net acute myeloid leukemia genetic classification as covariates. Patients with RUNX1 mutations showed a unique gene expression pattern with differential expression of 85 genes. The most prominently up-regulated genes in patients with RUNX1-mutated cytogenetically normal acute myeloid leukemia include lymphoid regulators such as HOP homeobox (HOPX), deoxynucleotidyltransferase (DNTT, terminal) and B-cell linker (BLNK), indicating lineage infidelity. Our findings firmly establish that RUNX1 mutations are a marker of poor prognosis and provide insights into the pathogenesis of RUNX1 mutation-positive acute myeloid leukemia.


Why don't stage-based activity promotion interventions work?
Despite the well-described benefits of regular physical activity, around 70% of adults in the UK fail to meet current activity recommendations. Interventions based on the Transtheoretical, or Stages of Change, Model of behaviour change have been proposed as one potentially effective method of promoting physical activity levels. However, two recent reviews have found little evidence that individualized stage-based activity promotion interventions are any more effective than control conditions in promoting long-term adherence to increased levels of physical activity. Possible reasons for this are: that exercise behaviour is a more complex group of behaviours than currently recognized; that many algorithms for determining current stage of activity change have not been validated; that exercise behaviour is determined by a number of factors not addressed by stage-based interventions; that the stages of change model encourages focus on stage progression which is not always associated with behaviour change; and that truly stage-based interventions are highly complex requiring more than one level of development and evaluation--a challenge that has not yet been met. Thus, stage-based activity promotion interventions may simplify exercise behaviour beyond what is useful for practitioners and health promoters. Paradoxically, stage-based activity promotion interventions that have been developed to date may have failed to appreciate the true complexity of the task.


Appearance of dark neurons following anodal polarization in the rat brain.
An anodal direct current of 3.0 microA or 30.0 microA was unilaterally applied for 30 min or 3 h to the surface of the sensorimotor cortex of rats, and the effects of polarization on the morphology of brain cells were examined by light microscopy. After five repeated anodal polarization trials, dark neurons appeared mainly in the polarized neocortex regardless of the intensity and duration of the polarizing currents. Such dark neurons were scarce in the control animals or the animals receiving only one trial of polarization. The dark neurons were most abundant in the second to fourth layers of the ipsilateral superior-lateral convexity of the frontal cortex, but a few were present in the contralateral cortex. The dark neurons began to appear 24 h after the last polarization; thereafter almost all of these neurons gradually reverted to their normal morphological profiles through a transitory state within 1 month of the last trial of repeated polarization. No morphological changes were apparent in any of the brain structures other than the cerebral cortex. These findings indicate that repeated anodal polarization has reversible morphological effects on the cortical neurons, suggesting that the appearance of dark neurons after anodal polarization is an important index for evaluation of cortical plastic change induced by polarization.


A new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from the Solomon ground skink, Sphenomorphus solomonis (Boulenger) (Sauria: Scincidae) from Papua New Guinea.
Between September 1990 and November 1991, 19 Sphenomorphus spp. skinks, including nine S. jobiense, three S. simus, and seven Solomon ground skinks, S. solomonis (Boulenger), were collected from Madang and Morobe Provinces, Papua New Guinea (PNG), and examined for coccidia. A single S. solomonis was found to be infected with a new species of Eimeria Schneider, 1875. Oöcysts of Eimeria perkinsae n. sp. are ellipsoidal with a smooth, colourless, bi-layered wall, measure 18.6 × 14.7 μm, and have a length/width (L/W) ratio of 1.3; both micropyle and oöcyst residuum are absent, but a fragmented polar granule is present. Sporocysts are ovoidal, 8.9 × 6.4 μm, L/W 1.4; neither Stieda, sub-Stieda or para-Stieda bodies are present; a sporocyst residuum consisted of a loose cluster of granules dispersed between sporozoites. Sporozoites are comma-shaped with spheroidal anterior and posterior refractile bodies. This represents the first report of coccidia from this skink genus.


The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.
Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch.


Reversible Adrenal Insufficiency in Three Patients With Post-Roux-en-Y Gastric Bypass Noninsulinoma Pancreatogenous Hypoglycemia Syndrome.
Objective. Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a disorder of endogenous hyperinsulinemia that is clinically distinguishable from insulinoma, with a greater preponderance after Roux-en-Y gastric bypass (RYBG). Hyperinsulinemic hypoglycemia can predispose to attenuation of counterregulatory hormone responses to hypoglycemia, and consequent suppression of the hypothalamic-pituitary-adrenal (HPA) axis. This case series describes 3 individuals who were diagnosed with adrenal insufficiency (AI) after undergoing RYGB, complicated by NIPHS. Methods. A retrospective chart review was performed for each individual. Chart review applied particular attention to the onset of hyperinsulinemic hypoglycemia following bariatric surgery and the dynamic testing leading to the diagnoses of NIPHS and AI. Results. In each case, reactive hypoglycemia ensued within months to years after RYGB. Cosyntropin stimulation testing confirmed the diagnosis of AI. Hydrocortisone therapy reduced the frequency and severity of hypoglycemia and was continued until successful medical and/or surgical management of hyperinsulinism occurred. Follow-up testing of the HPA axis demonstrated resolution of AI. In all cases, hydrocortisone therapy was finally discontinued without incident. Conclusion. We speculate that transient AI is a potential complication in patients who experience recurrent hyperinsulinemic hypoglycemia after RYGB. The putative mechanism for this observation may be attenuation of the HPA axis after prolonged exposure to severe, recurrent hypoglycemia. We conclude that biochemical screening for AI should be considered in individuals who develop post-RYGB hyperinsulinemic hypoglycemia. If AI is diagnosed, supportive treatment should be maintained until hyperinsulinemic hypoglycemia has been managed effectively.


A Physio-Morphological Trait-Based Approach for Breeding Drought Tolerant Wheat.
In the past, there have been drought events in different parts of the world, which have negatively influenced the productivity and production of various crops including wheat (Triticum aestivum L.), one of the world's three important cereal crops. Breeding new high yielding drought-tolerant wheat varieties is a research priority specifically in regions where climate change is predicted to result in more drought conditions. Commonly in breeding for drought tolerance, grain yield is the basis for selection, but it is a complex, late-stage trait, affected by many factors aside from drought. A strategy that evaluates genotypes for physiological responses to drought at earlier growth stages may be more targeted to drought and time efficient. Such an approach may be enabled by recent advances in high-throughput phenotyping platforms (HTPPs). In addition, the success of new genomic and molecular approaches rely on the quality of phenotypic data which is utilized to dissect the genetics of complex traits such as drought tolerance. Therefore, the first objective of this review is to describe the growth-stage based physio-morphological traits that could be targeted by breeders to develop drought-tolerant wheat genotypes. The second objective is to describe recent advances in high throughput phenotyping of drought tolerance related physio-morphological traits primarily under field conditions. We discuss how these strategies can be integrated into a comprehensive breeding program to mitigate the impacts of climate change. The review concludes that there is a need for comprehensive high throughput phenotyping of physio-morphological traits that is growth stage-based to improve the efficiency of breeding drought-tolerant wheat.


Gunnilactams A-C, Macrocyclic Tetralactams from the Mycelial Culture of the Entomogenous Fungus Paecilomyces gunnii.
Three novel macrocyclic tetralactams, gunnilactam A (1), gunnilactam B (2), and gunnilactam C (3), were isolated from the submerged fermentation broth of Paecilomyces gunnii, an entomogenous fungus identified as the anamorph of Cordyceps gunnii. Their structures were determined using NMR data, HREIMS, and single-crystal X-ray crystallography. Gunnilactam A exhibited selective cytotoxic activity against human prostate cancer C42B cells with an IC50 value of 5.4 μM.


Soft-tissue reconstruction in orthopedic surgery. Secondary procedures.
The original consulting microsurgeon should be present to assist in the identification and protection of the vascular pedicle during secondary procedures on microvascular transplants. Flap elevation, trimming, and bone graft placement should be completed during a single tourniquet time, whenever possible. Flaps can easily be resutured on the original bed while the tourniquet is still inflated. Although proximal pedicle transection is possible, it should be avoided by careful planning, because the transplanted tissue cannot be predictably expected to survive, especially with muscle transplants. The distal muscle should be transected only in situations in which the muscle inset is extremely complex. Transection in the extramuscular portion of the main pedicle may require prompt microsurgical repair in immature muscle transplants. The safest approach is to avoid the pedicle whenever additional secondary procedures are necessary following free microvascular tissue transplantation. Placement of vascular pedicles such that the anterior crest of the tibia is avoided if the Ilizarov technique is required permit uncomplicated distraction osteosynthesis. Simultaneous Ilizarov fixation and microvascular tissue transfer are safe, practical procedures for limb salvage. Placement of the Ilizarov fixator at the time of microvascular transplantation provides stable fixation and eliminates the need for a subsequent anesthetic for fixator placement. This form of stabilization, when performed at the time of microvascular tissue transfer, allows the orthopedic surgeon direct visualization of the fracture site as the fixator is placed and eliminates the need for placement of the fixation device through the transplanted tissue. Tissue expansion or suction lipectomy are sometimes needed to optimize the clinical result.


An unhealable wound: left by suicide.
This article is about the author's experience of being left by suicide and the effect the experience had on her work as an analyst in the consulting room and as a member of psychological organizations. The effects are generalized to others who have been left by suicide based on the writings of those left, and on writings of authors who have researched the subject. Shame and the effects the judgments of society now and in the past have on the person who suffers this experience are central, as well as the positive and negative ways groups are used by a person left by suicide to find solace and to emerge from the darkness of such abandonment. There is a constant longing (often unconscious) for replacement of the lost one. The article seeks to help analysts and those who have been left by suicide understand the suffering and the indelible mark that is experienced when there is a suicide of someone close. Understanding by the analyst is important in order to modulate the shame of this experience.


Intra-arterial digital subtraction angiography for children with idiopathic renal bleeding: a diagnosis of nutcracker phenomenon.
Among children with asymptomatic hematuria, 28 cases of nonglomerular idiopathic renal bleeding were subjected to this series of study. Intra-arterial digital subtraction angiography (DSA) and/or renal venography were performed to investigate the hematuria of unknown etiology. DSA clearly demonstrated the entrapment of the left renal vein (LRV), or nutcracker phenomenon in the majority of our patients (22 out of 28 cases): obstruction of the LRV with well-developed collaterals were found in 8 cases, and in the remaining 14 cases, various degrees of LRV compression were demonstrated. A characteristic real-time DSA image was the congestion of LRV associated with collaterals and/or intermittent venous flow at the compressed segment of LRV. The pullback pressures from LRV to the inferior vena cava (IVC) that were obtained from 5 of these patients demonstrated gradients of 2 mmHg (3 cases), 3 mmHg (1 case), and 5 mmHg (1 case), respectively. The parallel application of ultrasonography has given positive signs for LRV entrapment, although they have not necessarily coincided with the existing criteria of nutcracker phenomenon. Considering the high incidence of LRV entrapment among children with nonglomerular hematuria, most nutcracker phenomenon should be diagnosed on ultrasonography. However, intra-arterial DSA is an important tool to establish the disease entity and ultrasonic criteria.


Nanosecond UV lasers stimulate transient Ca2+ elevations in human hNT astrocytes.
Astrocytes respond to various stimuli resulting in intracellular Ca2+ signals that can propagate through organized functional networks. Recent literature calls for the development of techniques that can stimulate astrocytes in a fast and highly localized manner to emulate more closely the characteristics of astrocytic Ca2+ signals in vivo. In this article we demonstrate, for the first time, how nanosecond UV lasers are capable of reproducibly stimulating Ca2+ transients in human hNT astrocytes. We report that laser pulses with a beam energy of 4-29 µJ generate transient increases in cytosolic Ca2+. These Ca2+ transients then propagate to adjacent astrocytes as intercellular Ca2+ waves. We propose that nanosecond laser stimulation provides a valuable tool for enabling the study of Ca2+ dynamics in human astrocytes at both a single cell and network level. Compared to previously developed techniques nanosecond laser stimulation has the advantage of not requiring loading of photo-caged or -sensitising agents, is non-contact, enables stimulation with a high spatiotemporal resolution and is comparatively cost effective.


Cytoplasmic CXCR4 expression in breast cancer: induction by nitric oxide and correlation with lymph node metastasis and poor prognosis.
Lymph nodes constitute the first site of metastasis for most malignancies, and the extent of lymph node involvement is a major criterion for evaluating patient prognosis. The CXC chemokine receptor 4 (CXCR4) has been shown to play an important role in lymph node metastasis. Nitric oxide (NO) may also contribute to induction of metastatic ability in human cancers. CXCR4 expression was analyzed in primary human breast carcinoma with long-term follow-up. The relationship between nitrotyrosine levels (a biomarker for peroxynitrate formation from NO in vivo) and lymph node status, CXCR4 immunoreactivity, and other established clinico-pathological parameters, as well as prognosis, was analyzed. Nitrite/nitrate levels and CXCR4 expressions were assessed in MDA-MB-231 and SK-BR-3 breast cancer cell lines after induction and/or inhibition of NO synthesis. CXCR4 staining was predominantly cytoplasmic; this was observed in 50%(56/113) of the tumors. Cytoplasmic CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis. Kaplan-Meier survival curves showed that cytoplasmic CXCR4 expression was associated with reduced disease-free and overall survival. In multivariate analysis, cytoplasmic CXCR4 expression emerged as a significant independent predictor for overall and disease-free survival. Cytoplasmic expression of functional CXCR4 in MDA-MB-231 and SK-BR-3 cells was increased by treatment with the NO donor DETA NONOate. This increase was abolished by L-NAME, an inhibitor of NOS. Our data showed a role for NO in stimulating cytoplasmic CXCR4 expression in vitro. Formation of the biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in vivo. In addition, cytoplasmic CXCR4 expression may serve as a significant prognostic factor for long-term survival in breast cancer.


Surgery for ulcerative colitis in the era of the pouch: the St Mark's Hospital experience.
The choice of operation for ulcerative colitis among 422 patients having all their surgery at one hospital between 1976 (the year of the first restorative proctocolectomy) and 1990, was reviewed. The 15 year period was divided into three quinquennia (1976-80, 1981-85, 1986-90). Elective surgery was performed in 316 patients with one operative death. The proportions of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia were 36/60, 17/60, 4/60; 29/111, 30/111, 35/111; 30/145, 17/145, 75/145. Of 106 urgent operations with three postoperative deaths, 12 had a conventional proctocolectomy and 86 a colectomy with ileostomy and preservation of the rectum. Of 85 survivors of the latter there were two late deaths and in 13 no further surgery had been done at the time of this assessment. In the remaining 70 having subsequent surgery the proportion of conventional proctocolectomy, colectomy with ileorectal anastomosis, and restorative proctocolectomy for the three quinquennia respectively were 19/27, 4/27, 14/27; 11/21, 2/21, 8/21; 5/22, 4/22, 13/22. Of the 76 patients having colectomy with ileorectal anastomosis 12 (16%) no longer had a functioning rectum at the end of 1990. Of the 153 patients having an ileoanal pouch procedure, 11 (7%) no longer had, a functioning anus. The study showed an increase in the numbers of patients having elective surgery for ulcerative colitis during the three quinquennia. It also showed a rise of restorative over conventional proctocolectomy with diminution in elective colectomy with ileorectal anastomosis in the last five year period.


Robust and General Late-Stage Methylation of Aryl Chlorides: Application to Isotopic Labeling of Drug-like Scaffolds.
The preparation of isotopically labeled compounds for drug discovery and development presents a unique challenge. Both stable and radioactive isotopes must be incorporated into complex bioactive molecules as efficiently as possible, using precious, and often expensive, isotopically enriched reagents. Due to the ubiquity and importance of methyl groups in drug molecules, there is a requirement for a general, late-stage methylation that allows for the incorporation of both carbon and hydrogen isotopes. Herein, we report a highly efficient, robust palladium-catalyzed approach, optimized via high-throughput experimentation, for the methylation of aryl chlorides using potassium methyltrifluoroborate. A practically straightforward route to isotopically labeled methylating agents has also been developed, and the methodology applied to isotopologue synthesis, including the installation of isotopic labels in a range of drug-like scaffolds.


Performance enhancement for a GPS vector-tracking loop utilizing an adaptive iterated extended Kalman filter.
This paper deals with the problem of state estimation for the vector-tracking loop of a software-defined Global Positioning System (GPS) receiver. For a nonlinear system that has the model error and white Gaussian noise, a noise statistics estimator is used to estimate the model error, and based on this, a modified iterated extended Kalman filter (IEKF) named adaptive iterated Kalman filter (AIEKF) is proposed. A vector-tracking GPS receiver utilizing AIEKF is implemented to evaluate the performance of the proposed method. Through road tests, it is shown that the proposed method has an obvious accuracy advantage over the IEKF and Adaptive Extended Kalman filter (AEKF) in position determination. The results show that the proposed method is effective to reduce the root-mean-square error (RMSE) of position (including longitude, latitude and altitude). Comparing with EKF, the position RMSE values of AIEKF are reduced by about 45.1%, 40.9% and 54.6% in the east, north and up directions, respectively. Comparing with IEKF, the position RMSE values of AIEKF are reduced by about 25.7%, 19.3% and 35.7% in the east, north and up directions, respectively. Compared with AEKF, the position RMSE values of AIEKF are reduced by about 21.6%, 15.5% and 30.7% in the east, north and up directions, respectively.


Risk factors for sudden cardiac arrest in patients with ST-segment elevation myocardial infarction: a retrospective cohort study.
Sudden cardiac arrest (SCA) is a critical complication of acute myocardial infarction, especially ST-segment elevation myocardial infarction (STEMI). This study identified the risk factors for SCA in patients with STEMI before receiving catheterization. We retrospectively analyzed the data of patients with STEMI and cardiac arrest who presented to a tertiary care center in Taiwan between January 1, 2016, and December 31, 2019. Only patients with coronary artery disease (CAD) confirmed by coronary angiography were included in this study. We collected the patients' demographic and clinical data, such as age, sex, medical history, estimated glomerular filtration rate (eGFR), and coronary angiographic findings. The primary outcome of this study was SCA in patients with STEMI. Continuous and nominal variables were compared using the two-sample Student's t-test and chi-squared test, respectively. The results of logistic regression were subjected to multivariate analysis with adjustment for possible confounders. A total of 920 patients with STEMI and coronary angiography-documented CAD and 108 patients with SCA who presented between January 1, 2016, and December 31, 2019, were included. The bivariate logistic regression analysis of patients' demographic data revealed that patients with STEMI and SCA were slightly younger, were more likely to have diabetes mellitus, and had a lower eGFR than did the patients without SCA. The coronary angiographic findings indicated a higher prevalence of left main CAD and three-vessel disease in patients with SCA than in patients without SCA. Multivariate logistic regression revealed that left main CAD (odds ratio [OR]: 3.77; 95% confidence interval [CI], 1.84 to 7.72), a lower eGFR (OR: 0.97; 95% CI, 0.96 to 0.98), and younger age (OR: 0.98; 95% CI, 0.96 to 0.99) were the risk factors for SCA in patients with STEMI. Left main CAD, lower eGFR, and younger age are the risk factors for cardiac arrest in patients with acute myocardial infarction.


[Concept analysis of the nursing profession, published from 1994 to 2008].
Concept analysis is a research method in which concepts are examined in a logical and systematic fashion to form clear and rigorous conceptual definitions. To describe the concept analyses published between 1994 and 2008 and identify the emerging tendencies in the Nursing discipline, a two-staged study has been developed. In the first stage a systematic review of the literature was conducted: research published in the journals indexed in the MedLine, CINAHL and Cochrane databases were judged eligible, if they reported the theme of 'concept analysis' and 'nursing' in the title or in their key words and were published in English language. In the second stage, the articles that emerged were subjected to a content analysis. Some 158 concept analyses emerged, on average 10/year (range 1-22, median 11, +/- 5.6): these regarded 129 different concepts. Ninety-one (57.6%) concepts were focused on the nursing profession, while 67 (42.4%) were focused on the patients. Although in a few cases the effort made by the researchers moved toward the definition of new concepts, in others it appeared oriented toward including in Nursing some typical concepts from other disciplines, thus tracing an expansion of the domain of the Nursing discipline. Monitoring over time the concepts analysed constitutes an important research area to comprehend, both at a national and international level, the progressive evolution of the Nursing discipline.


Case report: Intraabdominal infection of Mycobacterium syngnathidarum in an immunocompetent patient confirmed by whole-genome sequencing.
The taxonomic group of non-tuberculous mycobacteria (NTM) encompasses more than 190 species and subspecies, some of which can cause pulmonary and extrapulmonary diseases across various age groups in humans. However, different subspecies exhibit differential drug sensitivities, and traditional detection techniques struggle to accurately classify NTM. Therefore, clinicians need more effective detection methods to identify NTM subtypes, thus providing personalized medication for patients. We present the case of a 47-year-old female patient diagnosed with an intraabdominal infection caused by Mycobacterium syngnathidarum. Despite computed tomography of the chest suggesting potential tuberculosis, tuberculosis infection was ruled out due to negative TB-DNA results for ascites fluid and sputum and limited improvement of lung lesions after treatment. Additionally, acid-fast staining and Lowenstein-Jensen culture results revealed the presence of mycobacterium in ascites fluid. Subsequent whole-genome sequencing (WGS) confirmed the DNA sequences of Mycobacterium syngnathidarum in colonies isolated from the ascites fluid, which was further corroborated by polymerase chain reaction and Sanger sequencing. Ultimately, the patient achieved a complete recovery following the treatment regimen targeting Mycobacterium syngnathidarum, which involved clarithromycin, ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid. This is the first reported case of Mycobacterium syngnathidarum infection in humans. Mycobacterium syngnathidarum was detected by WGS in this case, suggesting that WGS may serve as a high-resolution assay for the diagnosis of different subtypes of mycobacterium infection.


Action plans in asthma.
Action plans are recommended for most patients with persistent asthma to reduce the morbidity associated with this chronic disease. Unfortunately, despite these recommendations, this tool remains underused. The authors conducted a descriptive study at the asthma clinic of a tertiary care centre to determine the number of asthmatic patients presenting to a respiratory physician (new reference or follow-up visit) who possessed an individualized, written action plan, and to evaluate the patients' level of confidence and perceived efficacy toward their plans. In addition, for all patients in the study, the level of confidence in and the perceived efficacy of three different action plans (two traditional tools versus a simplified tool) were compared. A total of 92 asthmatic patients were included in the study. Overall, 46% of the patients possessed an action plan. The patients' average level of confidence and perceived efficacy toward their action plans were high (4.1 out of five and 3.3 out of four, respectively). When the three different action plans were compared, the level of confidence in and perceived efficacy of the traditional tools were similar, both being superior to the simplified tool. The number of asthmatic patients who presented to the asthma clinic and who possessed an action plan was higher than the reported Canadian mean of 10%; however, most of the patients were treated by specialized respiratory physicians, which may explain this improvement. Considering that most patients with persistent asthma should have an individualized, written action plan, the present study confirms that this tool is still not used for all asthmatic patients.


A Short Review on the Synthetic Strategies of Duocarmycin Analogs that are Powerful DNA Alkylating Agents.
The duocarmycins and CC-1065 are members of a class of DNA minor groove, AT-sequence selective, and adenine-N3 alkylating agents, isolated from Streptomyces sp. that exhibit extremely potent cytotoxicity against the growth of cancer cells grown in culture. Initial synthesis and structural modification of the cyclopropa[c] pyrrolo[3,2-e]indole (CPI) DNA-alkylating motif as well as the indole non-covalent binding region in the 1980s have led to several compounds that entered clinical trials as potential anticancer drugs. However, due to significant systemic toxicity none of the analogs have passed clinical evaluation. As a result, the intensity in the design, synthesis, and development of novel analogs of the duocarmycins has continued. Accordingly, in this review, which covers a period from the 1990s through the present time, the design and synthesis of duocarmycin SA are described along with the synthesis of novel and highly cytotoxic analogs that lack the chiral center. Examples of achiral analogs of duocarmycin SA described in this review include seco-DUMSA (39 and 40), seco-amino-CBI-TMI (13, Centanamycin), and seco-hydroxy-CBI-TMI (14). In addition, another novel class of biologically active duocarmycin SA analogs that contained the seco-iso-cyclopropylfurano[2,3-e]indoline (seco-iso-CFI) and seco-cyclopropyltetrahydrofurano[2,3-f]quinoline (seco-CFQ) DNA alkylating submit was also designed and synthesized. The synthesis of seco-iso-CFI-TMI (10, Tafuramycin A) and seco-CFQ-TMI (11, Tafuramycin B) is included in this review.


Enhanced surveillance of Clostridium difficile infection occurring outside hospital, England, 2011 to 2013.
There are limited national epidemiological data for community-associated (CA)-Clostridium difficile infections (CDIs). Between March 2011 and March 2013, laboratories in England submitted to the Clostridium difficile Ribotyping Network (CDRN) up to 10 diarrhoeal faecal samples from successive patients with CA-CDI, defined here as C. difficile toxin-positive diarrhoea commencing outside hospital (or less than 48 hours after hospital admission), including those cases associated with community-based residential care, with no discharge from hospital within the previous 12 weeks. Patient demographics and C. difficile PCR ribotypes were compared for CA-CDIs in our study and presumed healthcare-associated (HA) CDIs via CDRN. Ribotype diversity indices, ranking and relative prevalences were very similar in CA- vs HA-CDIs, although ribotypes 002 (p ≤ 0.0001),020 (p = 0.009) and 056 (p < 0.0001) predominated in CA-CDIs; ribotype 027 (p = 0.01) predominated in HA-CDIs. Epidemic ribotypes 027 and 078 predominated in institutional residents with CDI (including care/nursing homes) compared with people with CDI living at home. Ribotype diversity decreased with increasing age in HA-CDIs, but not in CA-CDIs. Ribotype 078 CA-CDIs were significantly more common in elderly people (3.4% (6/174) vs 8.7% (45/519) in those aged < 65 and ≥ 65 years, respectively; p = 0.019). No antibiotics were prescribed in the previous four weeks in about twofold more CA-CDI vs HAs (38.6% (129/334) vs 20.3% (1,226/6,028); p < 0.0001). We found very similar ribotype distributions in CA- and HA-CDIs, although a few ribotypes significantly predominated in one setting. These national data emphasise the close interplay between, and likely common reservoirs for, CDIs, particularly when epidemic strains are not dominant.


Dexamethasone phosphate in antibiotic ear drops for the treatment of acute bacterial otitis externa.
To compare the efficacy and safety of polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU/dexamethasone phosphate 0.1% (PN+Dx) otic solution with polymyxin sulfate 7500 IU/neomycin sulfate 3500 IU (PN-Dx) in patients with acute bacterial otitis externa (AOE), in order to determine the possible benefit of the addition of dexamethasone. Active controlled, double-blind, randomized, parallel group, multi-center clinical trial in ear, nose, and throat (ENT) specialist practices with a planned interim analysis for sample size adaptation. In total, 338 patients aged 18-76 who had a previous episode of otitis externa within the last year were randomized to receive 10 +/- 2 days of treatment with two drops, three times daily, of either PN+Dx or PN-Dx. Change in the clinical symptom score (consisting of the subscores redness, swelling, pain, and secretion) and of the visual analogue scale (VAS) rating for pain from Visit 1 (Day 1) to Visit 2 (Day 4 +/- 1), patient's assessment of efficacy at Visit 3 (Day 10 +/- 2), and the frequency and type of adverse events. There was a significantly greater reduction of swelling from Visit 1 to Visit 2 with PN+Dx, and more patients rated the efficacy of PN+Dx as 'very good' or 'good' at Visit 3 (p = 0.03). There was also a significantly greater decrease in the clinical symptom score from Visit 1 to Visit 2 in the PN+Dx group in patients who had at least a moderately severe symptom score with more than seven points at Visit 1 (p = 0.01) and in patients suffering from their current episode of otitis externa for more than 2 days (p = 0.02). In total, 14 adverse events were reported during the study period with no related adverse drug reactions for PN+Dx. The addition of dexamethasone phosphate to polymyxin B/neomycin significantly reduces swelling in patients with AOE and leads to significantly higher patient's ratings of treatment efficacy. It especially leads to an overall reduction of symptoms in cases of moderately or more severe otitis externa and cases lasting for more than 2 days.


General practitioner follow-up in older patients after an emergency department admission.
Few studies have investigated older patients with regards to general practice follow-up after an emergency department (ED) admission. We measured the proportion of older patients given explicit general practice follow-up instructions who sought care by day seven after an ED admission. Patients discharged from Fairfield Hospital ED (south-western Sydney) who were 65 years and older were approached for a structured telephone interview. Data from the interview and patients' ED discharge summaries were analysed descriptively. Exploratory statistical analyses were conducted to identify potential explanatory factors. Fifty patients participated in the study. Most participants (76%) attended general practice follow-up by day seven. Those with more relatives who could be called on for help were more likely to attend the follow-up appointment (P = 0.003). Participants who were not married (54% versus 84%) and non-drivers (53% versus 90%) were less likely to attend for follow-up. Close family support and car transport might influence general practice follow-up in older people. Further exploration of contributing factors may be warranted.


Low grade central chondrosarcoma of the fifth costotransverse joint.
Chondrosarcoma (CHS) is the third most frequent primary malignant tumour of bone exceeded only by myeloma and osteosarcoma. It usually occurs in the trunk bones (pelvic girdle, shoulder, ribs) followed by the femur and humerus and is very rare in the spine accounting for about 5% of all CHSs. The majority of patients affected are over 50 years old. We report a case of a 22-year-old woman with a 2-month history of pain on the right side of the upper thoracic spine. Complete imaging work-up with radiographs, CT, MRI and digital subtraction angiography showed an osteolytic lesion of the right transverse process of T5 with extension into the ipsilateral rib and enhancing extracompartmental tissue involving the paraspinal muscles. Both CT-guided core needle biopsy and excisional biopsy were consistent with grade I central CHS with myxoid change and focal areas of Grade II CHS.


Modelling the impacts of altered management practices, land use and climate changes on the water quality of the Millbrook catchment-reservoir system in South Australia.
Sustainable management of drinking water reservoirs requires taking into account the potential effects of their catchments' development. This study is an attempt to estimate the daily patterns of nutrients transport in the catchment - reservoir systems through the application of the ensemble of complementary models SWAT-SALMO. SWAT quantifies flow, nitrate and phosphate loadings originating in catchments before entering downstream reservoirs meanwhile SALMO determines phosphate, nitrate, and chlorophyll-a concentrations within the reservoirs. The study applies to the semi-arid Millbrook catchment-reservoir system that supplies drinking water to north-eastern suburbs of Adelaide, South Australia. The catchment hosts viti- and horticultural land uses. The warm-monomictic, mesotrophic reservoir is artificially aerated in summer. After validating the simulation results for both Millbrook catchment and reservoir, a comprehensive scenario analysis has been conducted to reveal cascading effects of altered management practices, land uses and climate conditions on water quality in the reservoir. Results suggest that the effect on reservoir condition in summer would be severe, most likely resulting in chlorophyll-a concentrations of greater than 40 μg/l if the artificial destratification was not applied from early summer. A 50% curbing of water diversion from an external pipeline to the catchment will slightly limit chlorophyll-a concentrations by 1.22% as an effect of reduced inflow phosphate loads. The simulation of prospective land use scenarios converting 50% of present pasture in the Millbrook catchment into residential and orchards areas indicates an increase of summer chlorophyll-a concentrations by 9.5-107.9%, respectively in the reservoir. Global warming scenarios based on the high emission simulated by SWAT-SALMO did result in earlier growth of chlorophyll-a but overall the effects on water quality in the Millbrook reservoir was not significant. However scenarios combining global warming and land use changes resulted in significant eutrophication effects in the reservoir, especially in the unmanaged condition with stratification in summer. This study has demonstrated that complementary model ensembles like SWAT-SALMO allow to comprehend more realistically cascading effects of distinct catchment processes on internal reservoir's processes, and facilitate integrated management scenarios.


Urea distribution kinetics analyzed by simultaneous injection of urea and inulin: demonstration that transcapillary exchange is rate limiting.
The kinetics of urea and inulin were studied after simultaneous i.v. injection in six anesthetized dogs. The distribution of both compounds was characterized by a three-compartment model. The initial volume of urea distribution averaged 2.21 +/- 0.39 liters (+/- S.D.) and was similar to the expected volume of intravascular space. Although the 0.66 +/- 0.05 liters/kg of total volume of urea distribution corresponds to total body water, transcapillary exchange between intravascular space and rapid and slow equilibrating interstitial fluid spaces is the rate-limiting step in urea distribution and accounts for the three-compartmental structure of the system used to model the distribution kinetics of both urea and inulin. The free-water diffusion coefficient ratio of urea and inulin and the intercompartment clearances calculated after the simultaneous injection of these compounds were used to estimate blood flows to the fast and slow equilibrating interstitial fluid compartments. The sum of these flows averaged 97% of measured cardiac output (range, 83-113%) and was not significantly different from cardiac output. These studies suggest that the rate of urea removal during dialysis may be affected by hemodynamic factors, as we have shown previously for drugs.


Grazing enhances belowground carbon allocation, microbial biomass, and soil carbon in a subtropical grassland.
Despite the large contribution of rangeland and pasture to global soil organic carbon (SOC) stocks, there is considerable uncertainty about the impact of large herbivore grazing on SOC, especially for understudied subtropical grazing lands. It is well known that root system inputs are the source of most grassland SOC, but the impact of grazing on partitioning of carbon allocation to root tissue production compared to fine root exudation is unclear. Given that different forms of root C have differing implications for SOC synthesis and decomposition, this represents a significant gap in knowledge. Root exudates should contribute to SOC primarily after microbial assimilation, and thus promote microbial contributions to SOC based on stabilization of microbial necromass, whereas root litter deposition contributes directly as plant-derived SOC following microbial decomposition. Here, we used in situ isotope pulse-chase methodology paired with plant and soil sampling to link plant carbon allocation patterns with SOC pools in replicated long-term grazing exclosures in subtropical pasture in Florida, USA. We quantified allocation of carbon to root tissue and measured root exudation across grazed and ungrazed plots and quantified lignin phenols to assess the relative contribution of microbial vs. plant products to total SOC. We found that grazing exclusion was associated with dramatically less overall belowground allocation, with lower root biomass, fine root exudates, and microbial biomass. Concurrently, grazed pasture contained greater total SOC, and a larger fraction of SOC that originated from plant tissue deposition, suggesting that higher root litter deposition under grazing promotes greater SOC. We conclude that grazing effects on SOC depend on root system biomass, a pattern that may generalize to other C4-dominated grasslands, especially in the subtropics. Improved understanding of ecological factors underlying root system biomass may be the key to forecasting SOC and optimizing grazing management to enhance SOC accumulation.


Scavenge-ROMP-filter: a facile strategy for soluble scavenging via norbornenyl tagging of electrophilic Reagents.
[reaction: see text] A new "chemical tagging" method for homogeneous electrophilic scavenging is described. The method utilizes 5-norbornene-2-methanol to scavenge/tag a variety of electrophiles that are present in excess. Once tagging is complete, the crude reaction mixture is subjected to a rapid ROM polymerization event utilizing the second generation Grubbs catalyst. This process yields a polymer that can be precipitated with methanol or ether/hexane, leaving products in excellent yield and purity.


General approach to the total synthesis of 9-methoxy-substituted indole alkaloids: synthesis of mitragynine, as well as 9-methoxygeissoschizol and 9-methoxy-N(b)-methylgeissoschizol.
Herein, the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3), and 9-methoxy-N(b)-methylgeissoschizol (4) are described. Initially, an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of D-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc-protected aniline 10b was crucial to the success of this heteroannulation. The alpha,beta-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)(2)-mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-N(b)-methylgeissoschizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1).


Comparison of psychiatric-mental health nursing education objectives: consumers, educators, and practitioners.
This consumer-nurse study was part of a larger project, Research in Mental Health Education, which compared the priorities of educators and practitioners within and between three core mental health professions and between the professionals and consumers. In the consumer-nurse portion of the study, the objectives for graduate education in psychiatric-mental health nursing were validated by psychiatric-mental health nursing educators (N=20) based in four university programs in the East, West, and Midwest. Another sample of nurse educators and practitioners in this specialty area, drawn from nine states, prioritized these objectives. A separate deck of objectives for mental health professionals was generated and prioritized by consumers (N=15) who were members of the Mental Health Association of Minnesota. Standardized procedures for generating and validating the objectives for nurses and consumers and the same task, the Priority Sort, were used by all subjects, nurses, and consumers, to prioritize the objectives. Similarities and differences between nurses and consumers are discussed. Differences between nurse educators and practitioners, which are statistically significant, also are described. Implications for consumer and practitioner input into curricular decisions are discussed as well as interdisciplinary courses that could conserve faculty time and budgetary resources.


Investigation of the Bonding Mechanism between Overlapping Textile Layers for FRP Repair Based on Dry Textile Patches.
Lots of damaged fiber-reinforced plastic (FRP) components are replaced by new components instead of repairing. Furthermore, only very labor-intensive repair methods are available on the market to fully restore the integrity of the structure. This requires a high level of experience or, alternatively, very cost-intensive technology, such as the use of computer tomography and robotics. The high costs and CO2 emissions caused by the manufacture of FRP components then bear no relation to their service life. The research project IGF-21985 BR "FRP-Repair" aims to solve the named challenges. Using semiconductor oxide catalysts, the matrix can be locally depolymerized by ultraviolet (UV) radiation, and thus removed from the damaged area of the FRP component. Subsequently, the damaged fibers in this area can be detached. By using customized textile repair patches and local thermoset reinfiltration, the repair area is restored. With this process, the fiber structure can be repaired locally with new fibers on the textile level. The repair is similar to the original production of a fiber composite in an infusion process. No additional adhesive material is used. As a result, repaired FRP structures with restored mechanics and a near-original surface can be realized. This article provides an insight into the actual steps of the development of the FRP component repair process using dry textile patches. The empirical investigation of overlapped rovings and UD material showed the expected results. Residual fracture forces of up to 86% could be achieved. The most interesting approach on the roving level was splicing the overlapping fibers. The free ends of the fibers of the patch and part are mechanically bonded. This bond at the textile level is further strengthened by infusion with matrix.


Identification of a pterin derivative in Escherichia coli DNA photolyase.
DNA photolyase from Escherichia coli contains reduced flavin adenine dinucleotide plus a second chromophore, partially characterized in previous studies. Both chromophores function as sensitizers in catalysis. The second chromophore has been identified as a 6-substituted pterin derivative. The compound is oxidized with permanganate to yield 6-carboxypterin or reduced with sodium cyanoborohydride to yield a 5,6,7,8-tetrahydropterin derivative. The second chromophore exhibits spectral properties (lambda max = 360, 255 nm, pH 2) similar to that observed for 7,8-dihydropterin cations. The compound does not exhibit a spectrally detectable pKa around 4 but is converted to a dication (lambda max = 346, 255 nm) in strong acid (pKa approximately 1). Similar ionization behavior is observed with 7,8-dihydropterin derivatives that are alkylated at N(5). The instability of the second chromophore in weakly alkaline solution is due to a fully reversible conversion to a labile bleached form. As compared with other pterin derivatives, the hydrolytic instability is unusual but is very similar to that observed for 5,6-dialkyl-7,8-dihydropterinium salts. It is proposed that the second chromophore is a 7,8-dihydropterin with substituents at positions 5 and 6. The discovery that a pterin derivative functions as a photosensitizer in DNA repair is apparently the first example of a photobiological function for pterins.


Degeneration of the intervertebral disc with new approaches for treating low back pain.
This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.


Treatment of hypophonia with collagen vocal cord augmentation in patients with parkinsonism.
We conducted structured interviews of patients with Parkinson's disease (PD) and other parkinsonian disorders and their caregivers after augmentation of vocal folds with collagen injections. A total of 12 patients (mean age, 73.7 +/- 8.6 years) completed the questionnaire after an average of 3.0 +/- 1.7 collagen injections, with an average of 13.8 +/- 7.4 weeks between each injection. In addition to improvement in all six voice quality questions, there was significant improvement (P < 0.05) in the Glascow Benefit Inventory (GBI) score. The injection procedure was tolerated well by patients with an average duration of benefit lasting 7.8 +/- 8.5 weeks. Augmentation of vocal folds with collagen provides temporary improvement in voice in patients with parkinsonian hypophonia.


Endothelial keratoplasty: the influence of preoperative donor endothelial cell densities on dislocation, primary graft failure, and 1-year cell counts.
The purpose of this study was to determine if an association exists between preoperative donor central endothelial cell density (ECD) and the complications of donor dislocation, iatrogenic primary graft failure (IPGF), and endothelial survival at 1 year after endothelial keratoplasty (EK) surgery. A prospective, nonrandomized, interventional case study was conducted evaluating 629 consecutive EK procedures. The preoperative donor ECD was recorded for each case. The mean preoperative ECD of the group of EK cases with postoperative donor dislocation was compared with the mean ECD of the group of EK cases that did not suffer donor dislocation. The subset of eyes that underwent Descemet stripping automated endothelial keratoplasty (DSAEK) was also evaluated for dislocation, IPGF, and ECD at 1 year. There were 31 eyes that suffered a dislocation in the overall group of 629 eyes (4.9% dislocation rate). The mean preoperative ECD of the donor tissue in this dislocation group was 2769 cells per square millimeter (range = 2147-3454 cells/mm). The mean preoperative ECD of the donor tissue in the group that did not dislocate (n = 598) was 2818 cells per square millimeter (range = 2110-4209 cells/mm). There was no significant difference in preoperative ECD between these groups (P = 0.428). There was a subset of 350 cases of DSAEK, of which 9 cases dislocated (2.6% dislocation rate). The mean preoperative ECD of the donor tissue in this dislocation group was 2604 cells per square millimeter (range = 2323-3175 cells/mm), with 5 of the 9 dislocation donors with a preoperative ECD above 2500 cells per square millimeter. The mean preoperative ECD of the donor tissue in the group that did not dislocate (n = 341) was 2825 cells per square millimeter (range = 2110-4209 cells/mm). There was no significant difference in preoperative ECD between these groups (P = 0.069). There was no significant correlation between preoperative ECD and the ECD at 1 year after DSAEK (n = 90; Pearson correlation = 0.184; P = 0.082). There were no IPGFs in the entire series of 350 consecutive DSAEK cases, and therefore, no statistical analysis is possible for IPGF. Preoperative donor ECD was not associated with donor dislocation for any form of EK surgery. Tissue with donor cell counts below 2500 cells per square millimeter can attach, and tissue with donor cell counts above 2500 cells per square millimeter can detach. Higher preoperative donor ECD was not correlated with higher ECD at 1 year postoperatively. Surgeons' requests for donor tissue with an ECD above 2500 cells per square millimeter for DSAEK surgery for the purpose of avoiding dislocations, IPGF, or improving 1-year ECD are not supported by this data.


An Efficient One-Pot Synthesis of Densely Functionalized Fused-Quinolines via Sequential Ugi4CC and Acid-Mediated Povarov-Type Reaction.
A divergent synthesis of fused-quinolines has been explored by performing Ugi four-component condensation and sulfuric acid promoted deprotection/Povarov-type reaction in one-pot. The process involves Ugi condensation of propiolic acids, aldehydes/ketones, aminoaldehyde acetals and isocyanides followed by sulfuric acid promoted deprotection and Povarov-type reaction with anilines in ethanol. This method enables straightforward access to the structurally diverse 2,3-dihydro-1H-pyrrolo[3,4-b]quinolin-1-ones (DHPQ), 3,4-dihydrobenzo[b][1,6]naphthyridin-1(2H)-ones (DHBN), and 2,3,4,5-tetrahydro-1H-azepino[4,3-b]quinolin-1-ones (THAQ), starting from readily available starting materials.


[Postoperative analgesic and anti-inflammatory effects of rofecoxib after total knee replacement].
To evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR). Thirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured. The pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05). Preoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.


Ultrasmall Gold Nanoparticles Coated with Zwitterionic Glutathione Monoethyl Ester: A Model Platform for the Incorporation of Functional Peptides.
Ultrasmall gold nanoparticles (AuNPs) are an emerging class of nanomaterials exhibiting distinctive physicochemical, molecular, and in vivo properties. Recently, we showed that ultrasmall AuNPs encompassing a zwitterionic glutathione monoethyl ester surface coating (AuGSHzwt) were highly resistant to aggregation and serum protein interactions. Herein, we performed a new set of biointeraction studies to gain a more fundamental understanding into the behavior of both pristine and peptide-functionalized AuGSHzwt in complex media. Using the model Strep-tag peptide (WSHPQFEK) as an integrated functional group, we established that AuGSHzwt could be conjugated with increasing numbers of Strep-tags by simple ligand exchange, which provides a generic approach for AuGSHzwt functionalization. It was found that the strep-tagged AuGSHzwt particles were highly resistant to nonspecific protein interactions and retained their targeting capability in biological fluid, displaying efficient binding to Streptactin receptors in nearly undiluted serum. However, AuGSHzwt functionalized with multiple Strep-tags displayed somewhat lower resistance to protein interactions and lower levels of binding to Streptactin than monofunctionalized AuGSHzwt under given conditions. These results underscore the need for optimizing ligand density onto the surface of ultrasmall AuNPs for improved performance. Collectively, our findings support ultrasmall AuGSHzwt as an attractive platform for engineering functional, protein-mimetic nanostructures capable of specific protein recognition within the complex biological milieu.


Forelimb blood flow distribution during hypothalamic dilator response.
An attempt is made to determine whether hypothalamically induced forelimb vascular dilation in the dog affects primarily exchange beds or shunt circuits. Slug injections of [131I] albumin and 86RbCl were used to measure the active vascular volume of the forelimbs and permeability surface area product (PS), respectively. Changes in total vascular volume (TVV), filtration, and capillary filtration coefficient (CFD) were measured by plethysmography. During stimulation, forelimb blood flow increased 25% and TVV increased an average 1.5 ml. There was no plethysmographic evidence of outward capillary filtration. Active vascular volume decreased 11%. PS decreased 11%, and CFC decreased 20%. These results point to a redistribution of blood flow from exchange circuits to faster flow channels. During constant-inflow perfusion, there was evidence from CFC and PS measurements that the capillary surface area was increased while active vascular volume decreased. The results observed with hypothalamic stimulation are different from those obtained with pharmacologic dilators and denervation. It is suggested that the former method has a more selective effect in lowering resistance in the faster shuntlike vessels.


Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS.
Cystathionine beta-synthase (CBS; EC 184.108.40.206) is a key enzyme in the generation of cysteine from methionine. A deficiency of CBS leads to homocystinuria, an inherited human disease characterized by mental retardation, seizures, psychiatric disturbances, skeletal abnormalities, and vascular disorders; however, the underlying mechanisms remain largely unknown. Here, we show the regional and cellular distribution of CBS in the adult and developing mouse brain. In the adult mouse brain, CBS was expressed ubiquitously, but it is expressed most intensely in the cerebellar molecular layer and hippocampal dentate gyrus. Immunohistochemical analysis revealed that CBS is preferentially expressed in cerebellar Bergmann glia and in astrocytes throughout the brain. At early developmental stages, CBS was expressed in neuroepithelial cells in the ventricular zone, but its expression changed to radial glial cells and then to astrocytes during the late embryonic and neonatal periods. CBS was most highly expressed in juvenile brain, and a striking induction was observed in cultured astrocytes in response to EGF, TGF-alpha, cAMP, and dexamethasone. Moreover, CBS was significantly accumulated in reactive astrocytes in the hippocampus after kainic acid-induced seizures, and cerebellar morphological abnormalities were observed in CBS-deficient mice. Taken together, these results suggest that CBS plays a crucial role in the development and maintenance of the CNS and that radial glia/astrocyte dysfunction might be involved in the complex neuropathological features associated with abnormal homocysteine metabolism.


Mechanisms of retroaxonal barrage firing in hippocampal interneurons.
We recently described a new form of neural integration and firing in a subset of interneurons, in which evoking hundreds of action potentials over tens of seconds to minutes produces a sudden barrage of action potentials lasting about a minute beyond the inciting stimulation. During this persistent firing, action potentials are generated in the distal axon and propagate retrogradely to the soma. To distinguish this from other forms of persistent firing, we refer to it here as 'retroaxonal barrage firing', or 'barrage firing' for short. Its induction is blocked by chemical inhibitors of gap junctions and curiously, stimulation of one interneuron in some cases triggers barrage firing in a nearby, unstimulated interneuron. Beyond these clues, the mechanisms of barrage firing are unknown. Here we report new results related to these mechanisms. Induction of barrage firing was blocked by lowering extracellular calcium, as long as normal action potential threshold was maintained, and it was inhibited by blocking L-type voltage-gated calcium channels. Despite its calcium dependence, barrage firing was not prevented by inhibiting chemical synaptic transmission. Furthermore, loading the stimulated/recorded interneuron with BAPTA did not block barrage firing, suggesting that the required calcium entry occurs in other cells. Finally, barrage firing was normal in mice with deletion of the primary gene for neuronal gap junctions (connexin36), suggesting that non-neuronal gap junctions may be involved. Together, these findings suggest that barrage firing is probably triggered by a multicellular mechanism involving calcium signalling and gap junctions, but operating independently of chemical synaptic transmission.


Single-dose methotrexate for the treatment of ectopic pregnancy: Our experience from 2010 to 2015.
To evaluate the success of systemic single-dose methotrexate (MTX) treatment in patients with ectopic pregnancy (EP) and to investigate factors related to treatment success. This retrospective study had been performed in Yildirim Beyazit University between January 2010 and December 2015. Demographic and clinical characteristics, ultrasonografic findings, pretreatment serum β-human chorionic gonadotropin (β-hCG) and progesterone levels of 58 patients with EP were retrieved from hospital records retrospectively. The patients were grouped according to MTX treatment success (response vs. failure). Single-dose MTX-treatment was successful in 72.4% (42/58) of patients. The mean pretreatment β-hCG level was significantly lower in responders than in failures (2080 ± 2322 vs. 5707 ± 3885 IU/L, p = 0.001), and 2678 IU/L was the most suitable cutoff to predict success (75% sensitivity, 73.8% specificity). Moreover, failure rate was 8.45 times more in group of patients whose β-hCG values were determined above the cutoff. The presence of fetal cardiac activity adversely affected treatment success (odds ratio = 12, p = 0.004). Treatment success was not affected by past history of ectopic pregnancy, thickness of endometrium, progesterone value or presences of pseudosac and free pelvic fluid. The success rate of single dose MTX in this study was 72.8 %, and we found that failure rate of MTX treatment was 8.45 times more in group of patients whose initial serum β-hCG values were above 2678 IU/L and 12 times more in patients with fetal cardiac activity.


Impact of Group 13 Metals on Cp2TiCl2 Reduction and Structural Characterization of Resulting Compounds.
The aim of the current study was to examine the effects of group 13 metals on Cp2TiCl2 reduction in the presence of 2-methoxyethanol (MeOEtOH) or ethanol (EtOH) and the compositions of the resulting products. Direct reaction of Cp2TiCl2 and M [Al, Al (Fe contaminated), Ga, In] in toluene/alcohol for 2 h gave a new family of uncommon homo- and heterometallic compounds: [Cp2Ti2Al(μ,η2-OEtOMe)4Cl2][Ti2(μ,η2-OEtOMe)3(η2-OEtOMe)2Cl4] (1), [Cp2Ti2Al(μ,η2-OEtOMe)4Cl2]Cl (2), [Cp2Ti2Al(μ,η2-OEtOMe)4Cl2][Cp2Ti(η2-HOEtOMe)][FeCl4] (3), [Cp2Ti(η2-HOEtOMe)][Ga2Cl6]0.25[Cl]0.5 (4), [Cp3Ti2(μ-OEt)2(OEt)][GaCl4] (5), [CpTi(μ,η2-OEtOMe)Cl]2 (6), and [Cp3Ti2(μ,η2-OEtOMe)(μ-OEtOMe)Cl] (7). The reaction with indium for 48 h resulted in isolation of [TiIn2(μ,η2-OEtOMe)4(OEtOMe)2Cl4] (8), [In2(μ-OEtOMe)2(HOEtOMe)4Cl4]2 (9), and [Ti(OEtOMe)4] (10). The complexes were characterized using elemental analysis, IR and NMR spectroscopies, and, for 1-9, single-crystal X-ray diffraction. The use of metallic gallium and indium to reduce Cp2TiCl2 opens up a previously unexplored path that may provide access to novel and unique compounds.