Combined diazepam and HDAC inhibitor treatment protects against seizures and neuronal damage caused by soman exposure.
The occurrence of status epilepticus (SE) is considered the main cause of brain lesions and morphological alterations, such as hippocampal neuron loss, that result in chronic epilepsy. Previous work demonstrated the convulsive and widespread neuropathological effects of soman, an organophosphorus compound that causes SE and severe recurrent seizures as a result of exposure. Seizures begin rapidly after exposure, can continue for hours, and contribute to prolonged physical incapacitation of the victim. This study attempts to identify anticonvulsive and neuroprotective drugs against soman exposure. Male Sprague-Dawley rats were exposed to 1.0 LD(50) soman. EEGraphical and neuropathological (Fluoro-Jade B staining) effects were analyzed at 72 h post-exposure to soman and subsequent treatments with diazepam (DZP) alone or in combination with histone deacetylase inhibitors, suberoylanilide hydroxamic acid (SAHA) or valproic acid (VPA). The extent of brain damage was dependent on the length of SE and not on the number of recurrent seizures. DZP treatment alone decreased SE time and damage in hippocampus, amygdala, thalamus and cortex, but not in piriform nuclei. The combination of DZP and VPA 100 mg/kg showed more anticonvulsive effects, decreased SE time, and afforded more neuroprotection in the hippocampus, mainly the ventral portion. The combination DZP and SAHA 25 mg/kg was more neuroprotective, but not more anticonvulsant than DZP alone. The DZP combination with VPA HDAC inhibitor proved to be a good treatment for SE and neuronal damage caused by soman exposure.


Study of enantioseparation of β-blockers using amylose tris(3-chloro-5-methylphenylcarbamate) as chiral stationary phase under polar-organic, reversed-phase and hydrophilic interaction liquid chromatography conditions.
In this study, we describe the experimental variables influencing enantioseparation of twelve β-blockers when analyzed under polar-organic, reversed-phase and hydrophilic interaction liquid chromatography conditions on a column with immobilized amylose tris(3-chloro-5-methylphenylcarbamate) as chiral stationary phase. Regarding polar-organic mode, two component mobile phases consisting of methanol, ethanol or acetonitrile with the addition of basic additives such as diethylamine, triethylamine, mono-ethanolamine, ethylendiamine or trifluoroacetic acid/diethylamine mixture were evaluated. Studies of retention at different temperatures were also performed. In reversed-phase mode, mixtures consisting of methanol or acetonitrile with either aqueous boric acid-borate buffer or sodium hydrogen carbonate-carbonate buffer solutions were compared aiming to study the influence of organic modifier as well as buffer type and pH on resolution. In addition, a systematic evaluation of the retention factors of β-blockers enantiomers in hydro-organic eluents containing acetonitrile in presence of diethylamine as additive was carried out by increasing progressively the water content, in order to check for retention dependencies indicative of the interplay of both hydrophilic interaction liquid chromatography and reversed-phase modes.


Sensory processing in Huntington's disease.
An intriguing electrophysiological feature of patients with Huntington's disease (HD) is the delayed latency and decreased amplitude of somatosensory long-latency evoked potentials (LLeps). We investigated whether such dysfunction was associated with delayed conscious perception of the sensory stimulus. Sixteen HD patients and 16 control subjects faced a computer screen showing the Libet's clock (Libet et al., 1983). In Rest trials, subjects had to memorize the position of the clock handle at perception of either electrical or thermal stimuli (AW). In React, additionally, they were asked to make a fist with their right hand, in a simple reaction time task (SRT). LLseps were recorded from Cz in both conditions. LLeps negative peak latency (N2) and SRT were abnormally delayed in patients in all conditions. AW was only abnormally prolonged in the React condition but the time difference between AW and the negative peak of the LLeps was not different in the two groups. There was a significant negative correlation between SRT and AW or LLeps amplitude in patients but not in healthy subjects. Our HD patients did not show abnormalities in conscious perception of sensory stimuli but their LLeps abnormalities were more marked when they had to react. This is compatible with failure to detect stimulus salience rather than with a cognitive defect. HD patients at early stages of the disease have preserved subjective perception of sensation but faulty sensorimotor integration.


Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents.
Triazine-linked triazole compounds (4a-j) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.


Low load, high repetition resistance training program increases bone mineral density in untrained adults.
High load, low repetition resistance training increases BMD in untrained adults; however, many older and untrained adults cannot maintain this type of strenuous program. Our goal was to evaluate whether a low load, high repetition resistance training program would increase BMD in untrained adults. Twenty sedentary, but otherwise healthy, adults (6 men and 14 women, age 28-63 yrs) completed a 27-week group exercise program. The participants were randomly assigned to one of two strength groups: one group completed full body, low load, high repetition weight training classes (S-WEIGHT), while the other group completed core focused fusion classes (S-CORE). Both groups also completed indoor cycling classes for cardiovascular conditioning. After a 3-week familiarization period, all participants completed a 12-week block of 5 fitness classes per week (3 cycling + 2 strength) and concluded with another 12-week block of 6 classes per week (3 cycling + 3 strength). We completed iDXA scans at baseline (week 3) and final (week 28). Compared to baseline, BMD significantly increased for S-WEIGHT in the arms (+4%, P<0.001), legs (+8%, P<0.01), pelvis (+6%, P<0.01) and lumbar spine (+4%, P<0.05), whereas BMD did not significantly change for S-CORE at any site. These results suggest that a low load, high repetition resistance training program may be an effective method to improve bone mass in adults.


Randomized, double-blind trial of guanfacine extended release in children with attention-deficit/hyperactivity disorder: morning or evening administration.
To examine the efficacy and tolerability of guanfacine extended release (GXR) administered in the morning or evening in children with attention-deficit/hyperactivity disorder (ADHD). In this multicenter, double-blind, placebo-controlled, dose-optimization study, children 6 to 12 years of age with ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the evening (GXR am), placebo in the morning and GXR in the evening (GXR pm), or twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV (ADHD-RS-IV). A total of 333 child participants received study drug in the following cohorts: GXR am (n = 107), GXR pm (n = 114), or placebo (n = 112). Mean (standard deviation) changes from baseline to week 8 (visit 10 or last observation carried forward) in ADHD-RS-IV total scores were significant for both GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR am: -19.8 [12.95]; GXR pm: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p < .001 for all). Most spontaneously-elicited treatment-emergent adverse events were mild or moderate in severity; the most common was somnolence (GXR all-active: 44.3%; GXR am: 46.7%; GXR pm: 42.1%; placebo: 12.5%). GXR administered either in the morning or evening was associated with significant and clinically meaningful improvements in ADHD symptoms. The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening. Clinical trial registration information-Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study.


Pharmacogenetics and schizophrenia.
Emergent pharmacogenetic studies indicate that the efficacy of antipsychotic medications in schizophrenia may be predicted through genetic analysis. There also is evidence that the side-effect profiles of second-generation antipsychotic medications and their propensity to cause weight gain, glucose and lipid abnormalities, and tardive dyskinesia may be predicted by pharmacogenetic analysis in this patient population. In the future, this targeted approach with the choice of antipsychotic medication based on the likelihood of clinical response and development of side effects in light of a particular patient's genetic status may gain hold as new treatments are developed with even fewer side effects.


Decomposition of roots in a Chihuahuan Desert ecosystem.
Mass losses of tethered buried roots of two woody shrubs and two herbaceous annuals buried in plots irrigated at 25 mm·month-1, 6 mm·week-1 and no irrigation were measured. At the end of 1 year, 10-15% of the mass of the herbaceous annual roots remained and 60% of the mass of woody shrub roots remained. There were no differences in mass loss attributable to added water. Rates of mass losses of roots in the Chihuahuan Desert were equal to or higher than those reported from mesic ecosystems. Roots of woody shrubs had relatively constant C:N ratios through the experiment. There was significant N immobilization in Baileya multiradiata roots. Percent mass loss of grass roots, Erioneuron pulchellum, and herbaceous annual roots, B. multiradiata, in plots with termites was 62% and in plots without termites was 15%. These data suggest that subterranean termites are responsible for most of the mass loss and mineralization of carbon and nitrogen in dead grass and herbaceous roots in the northern Chihuahuan Desert.


Methodological quality of guidelines for management of Lyme neuroborreliosis.
Many aspects of clinical management of Lyme neuroborreliosis are subject to intense debates. Guidelines show considerable variability in their recommendations, leading to divergent treatment regimes. The most pronounced differences in recommendations exist between guidelines from scientific societies and from patient advocacy groups. Assessment of the methodological quality of these contradictory guideline recommendations can be helpful for healthcare professionals. Systematic searches were conducted in MEDLINE and databases of four international and national guideline organizations for guidelines on Lyme neuroborreliosis published from 1999-2014. Characteristics (e.g., year of publication, sponsoring organization) and key recommendations were extracted from each guideline. Two independent reviewers assessed the methodological quality of each guideline according to the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. AGREE II scores from guidelines developed by scientific societies and from patient advocacy groups were compared across domains. We identified eight eligible guidelines of which n = 6 were developed by scientific societies and n = 2 by patient advocacy groups. Agreement on AGREE II scores was good (Cohen's weighted kappa = 0.87, 95% CI 0.83-0.92). Three guidelines, all from scientific societies, had an overall quality score of ≥ 50%. Two of them were recommended for use according to the AGREE II criteria. Across all guidelines, the AGREE II domain with the highest scores was "Clarity of Presentation" (65, SD 19%); all other domains had scores < 50% with the domain "Applicability" having the lowest scores (4, SD 4%). Guidelines developed by scientific societies had statistically significantly higher scores regarding clarity of presentation than guidelines from patient advocacy groups (p = 0.0151). No statistically significant differences were found in other domains. Current guidelines on Lyme neuroborreliosis vary in methodological quality and content. Health care providers and patients need to be aware of this variability in quality when choosing recommendations for their treatment decisions regarding Lyme neuroborreliosis. No statement can be given on quality of content and validity of recommendations, as these issues are not subject to assessment with the AGREE II tool and are prone to individual interpretation of the available evidence by the corresponding guideline panels. To enhance guideline quality, guideline panels should put more emphasis on linking recommendations to the available evidence, transparency in reporting how evidence was searched for and evaluated, and the implementation of recommendations into clinical practice.


Histamine H3-receptor activation augments voltage-dependent Ca2+ current via GTP hydrolysis in rabbit saphenous artery.
1. Actions of histamine on the voltage-dependent Ba2+(Ca2+) currents (IBa, ICa) were investigated using the whole-cell patch-clamp technique on dispersed smooth muscle cells from the rabbit saphenous artery. 2. Histamine (half-maximal dose, EC50 = 530 nM) augmented the IBa evoked by a brief depolarizing pulse (100 ms duration; to +10 mV from a holding potential of -80 mV) in a concentration-dependent manner. The maximum augmentation was obtained with 30 microM-histamine (1.29 times control). This augmentation of IBa was inhibited by the H3-antagonist, thioperamide (Ki = 30 nM, slope of the Schild plot = 1.0), but not by H1- or H2-antagonists (mepyramine or diphenhydramine, or cimetidine, respectively). 3. An H3-agonist, R alpha-methylhistamine (EC50 = 93 nM), also augmented IBa in a concentration-dependent manner at a holding potential of -80 mV and the maximum augmentation (1.25 times control) was obtained with 10 microM. This augmentation was also inhibited by thioperamide, but not by the above H1- and H2- antagonists. 4. Intracellularly applied 500 microM-guanosine 5'-triphosphate (GTP) enhanced, but 1 mM-guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) abolished, the histamine-induced augmentation of IBa. When one of the non-hydrolysable GTP analogues, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S; greater than 5 microM), guanylyl-imidodiphosphate (GMP-PNP; 200 microM) or guanylyl (beta, gamma-methylene)-diphosphonate (GMP-PCP; 1 mM) was intracellularly applied, the IBa amplitude evoked without the application of histamine was not affected, but the excitatory effect of histamine on IBa was reversed to an inhibition. Pre-treatment with pertussis toxin (PTX: 300 ng/ml and 3 micrograms/ml) did not modify the histamine-induced responses in the absence or presence of GTP gamma S. 5. 4 beta-Phorbol 12,13-dibutylate (PDBu) increased the amplitude of IBa. However, this action of PDBu was not enhanced by the application of GTP (500 microM) in the pipette, but additional application of histamine further increased the amplitude of IBa. Pre-treatment with a potent non-selective protein kinase inhibitor, 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7; 100 microM), did not modify the histamine-induced current augmentation or inhibition observed in the presence or absence of intracellular GTP gamma S.(ABSTRACT TRUNCATED AT 400 WORDS)


Incidence of postoperative acute kidney injury in patients with chronic kidney disease undergoing minimally invasive valve surgery.
We hypothesize that minimally invasive valve surgery in patients with chronic kidney disease (CKD) is superior to a conventional median sternotomy. We retrospectively analyzed 1945 consecutive patients who underwent isolated valve surgery. Included were patients with CKD stages 2 to 5. In-hospital mortality, composite complication rates, and intensive care unit and total hospital lengths of stay of those who underwent a minimally invasive approach were compared with those who underwent a standard median sternotomy. Resource use was approximated based on intensive care unit and total hospital lengths of stay. There were 688 patients identified; 510 (74%) underwent minimally invasive surgery, and 178 (26%) underwent a median sternotomy. There was no significant difference in mortality. Minimally invasive surgery was associated with fewer composite complications (33.1% vs 49.4%; odds ratio, 0.5; P ≤ .001), shorter intensive care unit (48 [interquartile range {IQR}, 33-74] hours vs 71 [IQR, 42-96] hours; P < .01), and hospital (8 [IQR, 6-9] days vs 10 [IQR, 8-15] days; P < .001) lengths of stay, and a lower incidence of acute kidney injury (8% vs 14.7%; odds ratio, 0.5; P = .01), compared with median sternotomy. In a multivariable analysis, minimally invasive surgery was associated with a 60% reduction in the risk of development of postoperative acute kidney injury. In patients with CKD undergoing isolated valve surgery, minimally invasive valve surgery is associated with reduced postoperative complications and lower resource use.


The pathogenesis of glaucoma in Sturge-Weber syndrome.
What is the cause of glaucoma in Sturge-Weber syndrome? Looking for the answer to this puzzling question, we examined 21 patients with the disease. Sixteen patients had gglaucoma: three bilateral and 13 unilateral. Episcleral hemangiomas were visible in all glaucomatous eyes. In general, the more extensive the hemangioma, the more severe was the glaucoma. During gonioscopy, blood could easily be made to reflux into Schlemm's canal of glaucomatous eyes. Often the canal separated into multiple fine channels. Episcleral venous pressure, which we measured in 11 patients, was high in all glaucomatous eyes. These observations suggest that glaucoma in Sturge-Weber syndrome is caused by elevated episcleral venous pressure. Most likely, veins draining aqueous from the canal of Schlemm are part of an intrascleral or episcleral hemangioma. The canal of Schlemm itself may be part of the hemangioma. Arteriovenous shunts in the hemangioma raise episcleral venous pressure, which in turn elevates intraocular pressure.


Improvement of cerebral CT abnormalities following liver transplantation in a patient with Wilson disease.
Cerebral CT performed in patients with Wilson disease (hepatolenticular degeneration) often reveals abnormalities of the putamen, globus pallidus, thalamocapsular region, cerebral cortex, dentate nucleus, and brain stem. We report a patient with Wilson disease who demonstrated rapid reversal of CT abnormalities following orthotopic liver transplantation.


A Proposal for Progression-Free Survival Assessment in Patients with Early Progressive Cancer.
Progression-free survival (PFS), which is evaluated in oncology clinical trials, is determined based on tumor progression evaluated according to an assessment schedule. There is possibly a bias in median PFS and hazard ratio (HR) for PFS depending on the assessment schedule referring to randomized controlled trials (RCTs) in patients with metastatic colorectal cancer. We re-analyzed the PFS in the FTD/TPI phase 2 trial by changing the assessment schedule. To assess biases in median PFS and HR for PFS resulting from different assessment schedules, we performed a computational simulation. The reanalysis of FTD/TPI phase 2 trial and the simulation results showed that there were biases in median PFS and HR for PFS. In RCTs for early progressive cancer, median PFS is dependent on the assessment schedule; however, HR for PFS can be assessed without clinically-meaningful differences between assessment schedules, regardless of biomarker assumptions.


Low-metastatic melanoma cells acquire enhanced metastatic capability via exosomal transfer of miR-199a-1-5p from highly metastatic melanoma cells.
The mean survival of metastatic melanoma is less than 1 year. While the high mortality rate is associated with the efficient metastatic colonization of the involved organs, the underlying mechanisms remain elusive. The role of exosomes in facilitating the interactions between cancer cells and the metastatic microenvironment has received increasing attention. Previous studies on the role of exosomes in metastasis have been heavily focused on cancer cell-derived exosomes in modulating the functions of stromal cells. Whether the extravasated neighboring cancer cells at the distant organ can alter the metastatic properties of one another, a new mechanism of metastatic colonization, has not been demonstrated prior to this report. In this study, a paired M4 melanoma derivative cell lines, i.e., M14-OL and POL, that we established and characterized were employed. They exhibit high (POL cells) and low (OL cells) metastatic colonization efficiency in vivo, respectively. We show that exosomal crosstalk between metastatic cancer cells is a new mechanism that underlies cancer metastasis and heterogeneity. Low metastatic melanoma cells (OL) can acquire the "metastatic power" from highly metastatic melanoma cells (POL). POL achieves this goal by utilizing its exosomes to deliver functional miRNAs, such as miR-199a-1-5p, to the targeted OL cell which in turn inactivates cell cycle inhibitor CDKN1B and augments metastatic colonization.


Amperometric biosensor for choline based on layer-by-layer assembled functionalized carbon nanotube and polyaniline multilayer film.
Conducting polymer film was prepared by electrochemical polymerization of aniline. Multiwalled carbon nanotubes (MWNTs) were treated with a mixture of concentrated sulfuric and nitric acid to introduce carboxylic acid groups to the nanotubes. By using the layer-by-layer method, homogeneous and stable MWNTs and polyaniline (PANI) multilayer films were alternately assembled on glassy carbon (GC) electrodes. Conducting polymer of PANI had three main functions: (i) excellent antiinterference ability, (ii) protection ability in favor of increasing the amount of the MWNTs immobilized on GC electrodes, and (iii) superior transducing ability. The protection effect of PANI film and the electrostatic interaction between positively charged PANI and negatively charged MWNTs both attributed to immobilizing abundant MWNTs stably, thereby enhancing the catalytic activity. The layer-by-layer assembled MWNTs and PANI-modified GC electrodes offered a significant decrease in the overvoltage for the H2O2 and were shown to be excellent amperometric sensors for H2O2 from +0.2V over a wide range of concentrations. As an application example, by linking choline oxidase (CHOD), an amplified biosensor toward choline was prepared. The choline biosensor exhibited a linear response range of 1x10(-6) to 2x10(-3) M with a correlation coefficient of 0.997, and the response time and detection limit (S/N=3) were determined to be 3 s and 0.3 microM, respectively. The antiinterference biosensor displays a rapid response and an expanded linear response range as well as excellent reproducibility and stability.


Development of electrochemical methods for determination of tramadol--analytical application to pharmaceutical dosage forms.
A square-wave voltammetric (SWV) method and a flow injection analysis system with amperometric detection were developed for the determination of tramadol hydrochloride. The SWV method enables the determination of tramadol over the concentration range of 15-75 microM with a detection limit of 2.2 microM. Tramadol could be determined in concentrations between 9 and 50 microM at a sampling rate of 90 h(-1), with a detection limit of 1.7 microM using the flow injection system. The electrochemical methods developed were successfully applied to the determination of tramadol in pharmaceutical dosage forms, without any pre-treatment of the samples. Recovery trials were performed to assess the accuracy of the results; the values were between 97 and 102% for both methods.


Prospective preference assessment of patients' willingness to participate in a randomized controlled trial of intensity-modulated radiotherapy versus proton therapy for localized prostate cancer.
To investigate patients' willingness to participate (WTP) in a randomized controlled trial (RCT) comparing intensity-modulated radiotherapy (IMRT) with proton beam therapy (PBT) for prostate cancer (PCa). We undertook a qualitative research study in which we prospectively enrolled patients with clinically localized PCa. We used purposive sampling to ensure a diverse sample based on age, race, travel distance, and physician. Patients participated in a semi-structured interview in which they reviewed a description of a hypothetical RCT, were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment, and completed a questionnaire assessing characteristics such as demographics and prior knowledge of IMRT or PBT. Patients' stated WTP was assessed using a 6-point Likert scale. Forty-six eligible patients (33 white, 13 black) were enrolled from the practices of eight physicians. We identified 21 factors that impacted patients' WTP, which largely centered on five major themes: altruism/desire to compare treatments, randomization, deference to physician opinion, financial incentives, and time demands/scheduling. Most patients (27 of 46, 59%) stated they would either "definitely" or "probably" participate. Seventeen percent (8 of 46) stated they would "definitely not" or "probably not" enroll, most of whom (6 of 8) preferred PBT before their physician visit. A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa.


Coronary Vasospasm as an Unexpected Cause of Intraoperative Hemodynamic Instability and Cardiac Arrest.
We present a case of intraoperative coronary artery vasospasm during thoracic surgery causing profound hemodynamic instability. A 68-year-old man undergoing completion right pneumonectomy exhibited intraoperative widespread ST elevation with associated hypotension. Transesophageal echocardiography performed by the anesthetist revealed hypokinetic apical and lateral walls, prompting transportation to the catheterization laboratory, with angiography demonstrating widespread coronary artery spasm. Intracoronary nitroglycerin relieved the vasospasm; however, heparin administration caused significant postoperative bleeding, resulting in cardiac arrest requiring resuscitation and return to the operating room. He ultimately recovered and was discharged to a rehabilitation facility 3 weeks later.


Two-dimensional Monte Carlo simulations of a colloidal dispersion composed of rod-like ferromagnetic particles in the absence of an applied magnetic field.
Influences of the magnetic interaction between particles and the aspect ratio of particles on aggregate structures in a colloidal dispersion composed of rod-like ferromagnetic particles were investigated by means of the cluster-moving Monte Carlo method. The internal structures of the aggregates obtained in simulations were analyzed in terms of the number density distribution of the clusters and radial distribution functions. The results show that as the magnetic interaction between particles increases, many small clusters such as anti-parallel particle pairs, raft-like clusters, and small loop-like clusters are formed; these gather to form larger aggregates. In the case of a relatively strong magnetic interaction between particles, solid-like rectangular clusters are formed when the aspect ratio is approximately 2, since the suitable distance between magnetic charges enables particles to form a fundamental structure of two normal anti-parallel particle pairs. As the aspect ratio increases beyond 2, many more stable raft-like clusters are formed, since the increase in distance between magnetic charges makes the two normal anti-parallel particle pair structures unstable. For a significantly larger aspect ratio, large network microstructures are produced by the formation of many chain-like and loop-like structures.


Pseudo-obstruction syndromes.
Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome characterized by symptoms and signs of intestinal occlusion, in absence of any mechanical obstruction of the gut lumen. It causes impaired transit of intestinal contents and is determined by abnormalities of motor activity. The term CIP is used to indicate a heterogeneous group of disorders with many different pathogenic mechanisms. The defect in the regulation of intestinal transit can be at any level of motility control. Two main types of CIP are recognized, termed respectively myogenic (when smooth muscle cells are affected) and neurogenic (caused by abnormalities of extrinsic and/or intrinsic nervous supplies). Both types may be secondary to a variety of recognizable diseases or idiopathic. In myogenic CIP, intestinal transit is impaired because of lack of propulsive strength; in the neurogenic form, contractions are powerful but not sufficiently co-ordinated to propel intestinal contents aborally in an organized fashion. CIP belongs to the large and loosely defined group of digestive functional disorders. These disorders probably share common pathogenic mechanisms but with different expressiveness. The reasons why only some patients present recurrent symptomatological bouts resembling mechanical occlusion has not been clarified. This aspect is of great clinical relevance and deserves attention, as CIP patients, unlike other patients with severe functional disorders, may undergo repeated, useless and potentially dangerous operations. The diagnosis of CIP may be suggested by clinical features and is based on radiological, endoscopic, manometric, and histological findings. Recent technological improvements facilitate the recognition of this intriguing syndrome. In particular, manometric recording of the small bowel motility, which has long been considered an important research technique, can now also be regarded as a useful diagnostic tool.


Compounds of wastewater origin in remote upland lakes in Ireland.
It is well established that persistent organic pollutants are transported long distances in the atmosphere and deposited into aquatic and terrestrial ecosystems in remote areas, including high altitude lakes. The objective of this research was to evaluate whether compounds of wastewater origin were present in four remote upland headwater lakes in Ireland that primarily receive loadings from atmospheric deposition. Using Polar Organic Chemical Integrative Samplers (POCIS) deployed in the lakes for 60 to 68 days, seven compounds were detected at levels that could be quantified but 25 of the target compounds were not detected. The detected compounds included the cannabinoid metabolite, tetrahydrocannabinol carboxylate (THC-COOH), codeine, acetaminophen (paracetamol), ibuprofen, and the artificial sweeteners, sucralose, and saccharin, which were all present at concentrations estimated to be < 125 ng/L. Caffeine was also present in the lakes at estimated concentrations between 213 and 1320 ng/L. Cocaine and tramadol were detected in POCIS deployed in some of the lakes, but at levels below the limits of quantitation. The highest concentrations of the target analytes were detected in two lakes located in the eastern part of Ireland. These data are consistent with regional atmospheric transport of these compounds originating from wastewater treatment plants in Ireland. However, contaminants from wastewater treatment plants in the United Kingdom may also be a source in these upland lakes that are located far from emissions of urban pollution.


Cortisol in deciduous tooth tissues: A potential metric for assessing stress exposure in archaeological and living populations.
Cortisol is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis that is regularly assessed in modern human and non-human populations in saliva, blood, and hair as a measure of stress exposure and stress reactivity. While recent research has detected cortisol concentrations in modern and archaeological permanent dental tissues, the present study assessed human primary (deciduous) teeth for cortisol concentrations. Fifty-one dentine and enamel samples from nine modern and 10 archaeological deciduous teeth were analyzed for cortisol concentrations via enzyme-linked immunosorbent assay (ELISA). Detectable concentrations of cortisol were identified in 15 (of 32) dentine and 8 (of 19) enamel samples coming from modern and archaeological deciduous teeth. This study is the first known analysis of cortisol from deciduous dental tissues, demonstrating the potential to identify measurable concentrations. The ability to analyze deciduous teeth is integral to developing dental cortisol methods with multiple potential future applications, including research on the biological embedding of stress in the skeleton. This study marks a key step in a larger research program to study stress in primary dentition from living and archaeological populations. Multiple samples generated cortisol values that were not detectable with ELISA. Minimum quantities of tissue may be required to generate detectable levels of cortisol. Future research should include larger sample sizes and consideration of intrinsic biological and extrinsic preservation factors on dental cortisol. Further method validation and alternative methods for assessing dental cortisol are needed.


Molecular conversions of recombinant staphylokinase during plasminogen activation in purified systems and in human plasma.
Recombinant staphylokinase (STAR) is produced as a 136 amino acid protein with NH2-terminal sequence Ser-Ser-Ser (mature STAR, HMW-STAR), which may be converted to lower molecular weight forms (LMW-STAR) by removal of the first six residues (yielding STAR-delta 6 with NH2-terminal Gly-Lys-Tyr-) or the first ten residues (yielding STAR-delta 10 with NH2-terminal Lys-Gly-Asp-). In the present study the occurrence and effects of these conversions during plasminogen activation by HMW-STAR were studied in purified systems and in human plasma. In stoichiometric mixtures of HMW-STAR and native human plasminogen (Glu-plasminogen), rapid and quantitative conversion of HMW-STAR to LMW-STAR occurred, concomitant with exposure of the active site in the plasmin-STAR complex. NH2-terminal amino acid sequence analysis revealed the sequence Lys-Gly-Asp- in addition to the known sequences of the Lys-plasmin chains, identifying STAR-delta 10 as the derivative generated from HMW-STAR. In mixtures of catalytic amount of HMW-STAR and human plasminogen, plasmin generation occurred progressively, following an initial lag phase, during which HMW-STAR was converted to LMW-STAR. Plasmin-mediated conversion of HMW-STAR to LMW-STAR obeyed Michaelis-Menten kinetics with Km = 3.6 microM and k2 = 0.38 s-1. The specific clot lysis activities of HMW-STAR (122,000 +/- 8,000 units/mg) and LMW-STAR (129,000 +/- 8,000 units/mg) were indistinguishable. In an in vitro system consisting of a 60 microliters plasma clot submerged in 250 microliters plasma, 80% clot lysis within 1 h was obtained with 70 nM HMW-STAR.(ABSTRACT TRUNCATED AT 250 WORDS)


Cytochemical staining characteristics of peripheral nodes of Ranvier in hexacarbon intoxication.
Changes in the distribution of stainable gap substance and subaxolemmal density at peripheral nodes of Ranvier in hexacarbon-intoxicated rats have been studied by light and electron microscopy. Cupric ion binding to the nodal gap substance was seen in normal nodes as a discrete annulus by the formation with ferrocyanide of Hatchett's Brown reaction product. Staining of osmicated fibres with ferrocyanide ions alone gave a deposit of black reaction product at the subaxolemmal region at nodes of Ranvier. Paranodal distension by neurofilamentous masses and separation of the terminal myelin loops in the early phase of paranodal dilatation produced no change in the distribution of the two kinds of stainable material. Paranodal myelin retraction with increases both in nodal gap width and nodal axon diameter resulted in displacement and attenuation of both stained regions. Axonal protrusion at the nodal region tended only to displace the stained gap substance, but sometimes it resulted in its attenuation. Occasionally loss of subaxolemmal staining was found. The possible functional relevance of these abnormal findings is discussed in relation to changes in conduction in affected nerves.


Roux-en-Y gastric bypass reversal: a systematic review.
Due to the large number of Roux-en-Y gastric bypass surgeries performed over the last decade, reversal of the bypass to normal anatomy has been increasingly reported. University affiliated Teaching Hospital, United States. The aim of this systematic review was to summarize the literature data regarding the indications, technical considerations, and outcomes of gastric bypass reversal. PubMed/MEDLINE search was conducted for articles reporting reversal of gastric bypass to normal anatomy. Patients' demographic characteristics, primary reason for reversal, reversal technique, and postreversal events were retrieved and categorized from each eligible paper. Thirty-five articles encompassing a total of 100 patients were eligible. Malnutrition was the most common indication for reversal (12.3%), followed by severe dumping syndrome (9.4%), postprandial hypoglycemia (8.5%), and excessive weight loss (8.5%). Techniques for gastrogastrostomy were available in 42 patients, with the hand-sewn technique as the most common (67.4%) followed by the linear stapler (23.2%) and the end-to-end anastomosis stapler used in 3 patients (6.9%). The reversal technique was performed endoscopically and described in 3 studies (3 patients). Techniques for handling the Roux limb were described in 56 patients (56%); the limb was reconnected in 32 patients (57.2%) and resected in 24 patients (42.8%). Weight regain was the most prevalent postreversal event (28.8%), followed by severe gastroesophageal reflux diseases (10.2%) and persistent abdominal pain (6.8%). There was no reported mortality. Gastric bypass reversal is indicated for excessive weight loss, dumping syndrome, and postprandial hypoglycemia. The procedure is well tolerated and feasible when performed laparoscopically and has no reported mortality.


Biological responses related to agonistic, antagonistic and synergistic interactions of chemical species.
The fact that the essential or toxic character of elements is species specific has encouraged the development of analytical strategies for chemical speciation over the last twenty years; indeed, there are now a great number of them that provide very good performance. However, biological systems are exposed to a complex environment in which species of elements can interact in a synergistic/antagonistic fashion. Thus, the metabolism of trace elements cannot be considered in isolation. On the other hand, biological systems are dynamic, so it is necessary to study the trafficking of species of elements between organs, tissues or cell compartments in order to decipher the biochemical processes of the interactions in which they are involved. Although the application of liquid chromatography-inductively coupled plasma-based "metallomics" methods in combination with organic mass spectrometry can provide much-needed insight, new analytical strategies are required to really understand the role of species of elements in biological systems and the mechanisms of their interactions. In the present paper, the interactions of the most widely studied elements in this context (Se, Hg and As) are discussed, as well as other important interactions between different elements.


Ureteroscopy in the elderly: safety and functional results.
To evaluate the effectiveness and safety of ureteroscopy (URS) for urinary stones treatment in patients ≥ 80 years of age. From 2012 to 2021, 96 patients ≥ 80 years underwent URS for urinary stone disease. Patients' demographics and surgical outcomes were examined. The median length of follow-up was 25 months. Median age was 84 years. Half of the patients (53%) were ASA score 3 and 16% ASA 4. Mean stone diameter (SD) was 10.6 mm, and mean procedure time was 78 min. Eighty-three patients underwent follow-up imaging (ultrasonography or computed tomography) with a median time of 31 days. Stone-free rate was 73.9%. Twenty patients (20.7%) experienced a minor complication [Clavien-Dindo (CD) I-II] whereas five (5.7%) experienced a major complication (CD III-V). SD ≥ 10 mm predicted CD III-V complications (OR 1.25, 95% CI 1.01-1.55, p = 0.03). Urinary drainage prior the procedure with double J stent, nephroureteral stent or percutaneous nephrostomy tube had no impact on patients' SFR [74.6% in the drained group versus 64.0% in the undrained group (p = 0.44)] nor on major complications (OR 4.68, 95% CI 0.25-87.77, p = 0.30). In elderly patients, URS for treatment of renal and ureteral stones is a relatively efficient and safe procedure. The risk of major complications is low, and the only associated risk factor found was SD ≥ 10 mm. Urinary drainage prior the procedure did not affect patients' outcomes.


Eradication of Helicobacter pylori in a Living Donor Liver Transplant Recipient With Immunosuppressive Therapy of Cyclosporine A: A Case Report.
A 54-year-old woman underwent living donor liver transplantation (LDLT) for primary biliary cholangitis (PBC) three years earlier. She took cyclosporine A (CyA) 150 mg/day as immunosuppression for prevention of rejection and PBC recurrence. Routine upper gastrointestinal endoscopy showed chronic atrophic gastritis and hyperplastic polyp, and rapid urease test was positive. Anti-Helicobacter pylori (H. pylori) serum IgG was elevated to 51 U/ml. We performed H. pylori eradication therapy with amoxicillin, clarithromycin and lansoprazole measuring the blood CyA concentration every day. Although the blood CyA concentration reached a peak (the concentration 2 hours after the administration: 818 ng/ml) on the second day, she did not develop renal dysfunction or other obvious adverse effects. Five weeks after the treatment, we confirmed eradication of H. pylori with the urea breath test. We herein reported a case of successful eradication of H. pylori in a LDLT recipient on immunosuppressive therapy with CyA without adverse effects.


Inhibition by adiponectin of IL-8 production by human macrophages upon coculturing with late apoptotic cells.
Adiponectin, an adipocyte-derived hormone, reportedly suppresses the production of TNF-alpha and IL-6 by LPS-stimulated human or porcine macrophages, and the phagocytosis of microbeads by human macrophages. In this study, we used a high molecular weight form of adiponectin purified from human plasma to examine its effects on the phagocytosis of late apoptotic cells by human macrophages and the subsequent IL-8 production. Adiponectin suppressed both the phagocytosis of apoptotic cells and the IL-8 production. In contrast, adiponectin augmented both the phagocytosis of apoptotic cells and the IL-8 production in the presence of LPS. These results suggest that adiponectin is not an anti-inflammatory hormone but rather a dual modulator of innate responses.


Platythorax progresses with lung involvement in pleuroparenchymal fibroelastosis.
Patients diagnosed with pleuroparenchymal fibroelastosis (PPFE) exhibit unique clinical features, including upper lobe-dominant lung involvement and platythorax (or flattened thoracic cage). Although platythorax have been shown to be a sign of disease progression, the temporal relationship between the progression of platythorax and the extent of lung involvement has not been closely investigated. We retrospectively investigated patients diagnosed with PPFE, who did not exhibit fibrotic lesions other than PPFE in the lower lobes. We estimated the fibrosis score, which is a visual score indicating the percentage of lung parenchyma occupied by the disease on computed tomography images selected every 2 cm from the lung apex to the lung base, and the flat chest index (the ratio of the anteroposterior diameter of the thoracic cage to the transverse diameter of the thoracic cage). Additionally, we investigated serial changes in the flat chest index and fibrosis score. A total of 29 patients were included in this study. The fibrosis score was found to be weakly and inversely correlated with forced vital capacity %predicted at the diagnosis (r = -0.40, p = 0.038). Furthermore, the annual changes in the flat chest index and fibrosis score was found to be moderately and inversely correlated (r = -0.663, p = 0.0037). These results indicate that there is a causal relationship between the progression of fibroelastosis and that of platythorax in patients with PPFE.


Race, explicit racial attitudes, implicit racial attitudes, and COVID-19 cases and deaths: An analysis of counties in the United States.
To examine the potential moderating effects of explicit racial attitudes and implicit racial attitudes on the relationship between percent of Black county residents and COVID-19 cases and deaths. We collected data from a variety of publicly available sources for 817 counties in the US. (26% of all counties). Cumulative COVID-19 deaths and cases from January 22 to August 31, 2020 were the dependent variables; explicit racial attitudes and implicit racial attitudes served as the moderators; subjective poor or fair health, food insecurity, percent uninsured, percent unemployed, median family income, percent women, percent of Asian county resident, percent of Hispanic county residents, and percent of people 65 or older were controls. The percent of Black county residents was positively associated with COVID-19 cases and deaths at the county level. The relationship between percent of Black residents and COVID-19 cases was moderated by explicit racial attitudes and implicit racial attitudes. Implicit racial attitudes can take on a shared property at the community level and effectively explain racial disparities. COVID-19 cases are highest when both the percent of Black county residents and implicit racial attitudes are high.


Methylcobalamin induces a long-lasting enhancement of the postsynaptic field potential in hippocampal slices of the guinea pig.
Methylcobalamin (CH3-B12) enhanced postsynaptic field potential (PSP) elicited from hippocampal slices (around 180% at a maximum), lasting more than 1 h after washing out, while it had no effect on antidromic spike potential (AP). By contrast, cyanocobalamin containing CN- instead of CH3- showed no enhancement in the PSP amplitude, suggesting that CH3- plays an important role for the PSP enhancement by methylcobalamin. The treatment with N-methyl-D-aspartate (NMDA) receptor specific antagonist, DL-2-amino-5-phosphonovaleric acid (APV) inhibited methylcobalamin-induced PSP enhancement by 50%, suggesting that NMDA receptor is partially relevant to the formation of this enhancement. Glutamate release from electrically stimulated slices was not enhanced by the treatment with methylcobalamin, suggesting that methylcobalamin affects the postsynaptic sites in hippocampal neurons. In whole cell voltage clamp recordings using cultured hippocampal neurons, methylcobalamin increased the currents elicited by NMDA time-dependently. These results may indicate that CH3- is required to modulate the PSP amplitude at the postsynaptic site and at least, NMDA receptor is involved in the formation of long-lasting PSP potentiation induced by methylcobalamin.


Kinetics of drug-induced changes in dopamine and serotonin metabolite concentrations in the CSF of the rat.
Cerebrospinal fluid (CSF) was removed at a constant flow rate of 1 microliter/min from the third ventricle of anesthetized rats. Every 15 min, CSF dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined by direct injection of CSF into a liquid chromatographic system coupled with electrochemical detection. Mean CSF concentrations of DOPAC, HVA, and 5-HIAA were 1.29 microM, 0.88 microM, and 2.00 microM, respectively. In order to determine the turnover rates of dopamine (DA) and serotonin, experiments using monoamine oxidase (MAO) inhibition were performed. Tranylcypromine (20 mg/kg i.p.) induced a sharp exponential decrease of CSF DOPAC, HVA, and 5-HIAA, with respective half-lives of 15.60 min, 16.91 min, and 77.23 min. Their respective turnover rates were 3.74, 2.22, and 1.18 nmol X ml-1 X h-1. m-Hydroxybenzylhydrazine (NSD-1015, 100 mg/kg i.p.) and monofluoromethyl-DOPA (100 mg/kg i.p.), two decarboxylase inhibitors, induced a slow exponential decrease of all three CSF metabolites. alpha-Methyl-p-tyrosine (250 mg/kg i.p.) also induced a slow exponential decrease of DOPAC and HVA. These decreases of CSF DOPAC and HVA induced by DA synthesis inhibitors may reflect the turnover of DA in vivo. Haloperidol (0.5 mg/kg i.p.) considerably enhanced CSF DOPAC and HVA without affecting 5-HIAA, confirming that dopaminergic receptors modulate DA neurotransmission in vivo. Haloperidol administered 1.5 h after NSD-1015 did not increase DOPAC and HVA, in contrast to reserpine (5 mg/kg i.p.) injected under the same conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


PhenoImageShare: an image annotation and query infrastructure.
High throughput imaging is now available to many groups and it is possible to generate a large quantity of high quality images quickly. Managing this data, consistently annotating it, or making it available to the community are all challenges that come with these methods. PhenoImageShare provides an ontology-enabled lightweight image data query, annotation service and a single point of access backed by a Solr server for programmatic access to an integrated image collection enabling improved community access. PhenoImageShare also provides an easy to use online image annotation tool with functionality to draw regions of interest on images and to annotate them with terms from an autosuggest-enabled ontology-lookup widget. The provenance of each image, and annotation, is kept and links to original resources are provided. The semantic and intuitive search interface is species and imaging technology neutral. PhenoImageShare now provides access to annotation for over 100,000 images for 2 species. The PhenoImageShare platform provides underlying infrastructure for both programmatic access and user-facing tools for biologists enabling the query and annotation of federated images. PhenoImageShare is accessible online at http://www.phenoimageshare.org .


Calcium microemboli and microfilters in valve operations.
Fatal microemboli occurred in 3 of 100 consecutive patients having aortic valve replacement; 2 occurred during perfusion before the microfilter era, and 1 occurred intraoperatively despite the use of in-line filters. In all 3 patients cerebral symptoms were present immediately postoperatively, and each died of severe brain damage. On postmortem examination cerebral calcium microemboli were verified in only 2 patients, although the brain of each patient contained minute infarctions. However, calcium particles were found in the kidneys of all 3 patients. Thus the kidneys proved to be the best place for detection of calcium emboli on postmortem examination. Although the microfilters currently available effectively prevent microemboli during extracorporeal circulation, the surgeon should be aware that embolization can also occur immediately after discontinuation of perfusion. The means of protecting the patient from this are discussed.


Studies on avian infectious bronchitis virus (IBV). II. Propagation of IBV in several cultured cells.
The growth of ten strains of avian infectious bronchitis virus (IBV) in several cultured cells was examined. The cultured cells used were chick kidney (CK), chick embryo (CE), HeLa and BHK-21 cells. The results obtained can be summarized as follows. 1. All the strains showed similar growth curves in CK cells. Progeny viruses appeared in the culture medium 4 to 6 hours after inoculation and peak virus titers of 10(6.5)--10(8.5) TCID50 per 0.1 ml were obtained after 36 hours. A cytopathogenic effect (CPE) was detected within 24 hours. No distinct CPE and low multiplicities were observed on culturing at 30 degrees C. 2. All strains replicated in CE cells, although only small amounts of virus were produced. No CPE was observed. 3. Only Beaudette-42 and Holte strains grew in BHK-21 cells. 4. No IBV strains grew in HeLa cells.


Self-Stabilized and Strongly Adhesive Supramolecular Polymer Protective Layer Enables Ultrahigh-Rate and Large-Capacity Lithium-Metal Anode.
Constructing a solid electrolyte interface (SEI) is a highly effective approach to overcome the poor reversibility of lithium (Li) metal anodes. Herein, an adhesive and self-healable supramolecular copolymer, comprising of pendant poly(ethylene oxide) (PEO) segments and ureido-pyrimidinone (UPy) quadruple-hydrogen-bonding moieties, is developed as a protection layer of Li anode by a simple drop-coating. The protection performance of in-situ-formed LiPEO-UPy SEI layer is significantly enhanced owing to the strong binding and improved stability arising from a spontaneous reaction between UPy groups and Li metal. An ultrathin (approximately 70 nm) LiPEO-UPy layer can contribute to stable and dendrite-free cycling at a high areal capacity of 10 mAh cm-2 at 5 mA cm-2 for 1000 h. This coating together with the promising electrochemical performance offers a new strategy for the development of dendrite-free metal anodes.


Demystifying evidential Dempster Shafer-based CNN architecture for fetal plane detection from 2D ultrasound images leveraging fuzzy-contrast enhancement and explainable AI.
Ultrasound imaging is a valuable tool for assessing the development of the fetal during pregnancy. However, interpreting ultrasound images manually can be time-consuming and subject to variability. Automated image categorization using machine learning algorithms can streamline the interpretation process by identifying stages of fetal development present in ultrasound images. In particular, deep learning architectures have shown promise in medical image analysis, enabling accurate automated diagnosis. The objective of this research is to identify fetal planes from ultrasound images with higher precision. To achieve this, we trained several convolutional neural network (CNN) architectures on a dataset of 12400 images. Our study focuses on the impact of enhanced image quality by adopting Histogram Equalization and Fuzzy Logic-based contrast enhancement on fetal plane detection using the Evidential Dempster-Shafer Based CNN Architecture, PReLU-Net, SqueezeNET, and Swin Transformer. The results of each classifier were noteworthy, with PreLUNet achieving an accuracy of 91.03%, SqueezeNET reaching 91.03% accuracy, Swin Transformer reaching an accuracy of 88.90%, and the Evidential classifier achieving an accuracy of 83.54%. We evaluated the results in terms of both training and testing accuracies. Additionally, we used LIME and GradCam to examine the decision-making process of the classifiers, providing explainability for their outputs. Our findings demonstrate the potential for automated image categorization in large-scale retrospective assessments of fetal development using ultrasound imaging.


A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors.
A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G2/M phase further confirming their ability to inhibit tubulin polymerisation.


Inhibition of gastrointestinal transit by morphine and FK 33-824 in the rat and comparative narcotic antagonist properties of naloxone and its N-methyl quaternary analog.
Morphine and the enkephalin-like peptide FK 33-824 given i.p. to rats potently inhibit gastrointestinal transit of a charcoal test meal, the doses inhibiting transit by 50% being respectively about 10 and 1 microgram/kg. These intestinal effects are opiate-specific, locally elicited and presumably involve the same action site since they are reversed by the "peripherally selective" narcotic antagonist N-methyl naloxone with apparent pA2 values of 7.34 and 7.10 respectively against morphine and FK 33-824. The calculated pA2 value for naloxone/morphine with the same in vivo test procedure (8.83) and the relative ability of naloxone and N-methyl naloxone to prevent 3H-etorphine binding to rat brain membranes (IC50 43 and 541 nM), indicate different potency ratios between the two narcotic antagonists in the in vitro binding cell-free system (about 1:10) and in vivo (about 1:30), but the latter ratio agrees with published findings in the isolated guinea pig ileum.


Time from blood draw to multiple electrode aggregometry and association with platelet reactivity.
Results from multiple electrode aggregometry (MEA) may vary according to pre-analytic factors. This study aimed to analyze the association of time from blood draw to MEA in patients undergoing percutaneous coronary intervention (PCI). In this observational single-center cohort study, platelet aggregation (aggregation units, U) was quantified by MEA (Multiplate Analyzer) after stimulation with adenosine diphosphate (ADP; final concentration [Fc] 6.4 μM), thrombin receptor activating peptide (TRAP; Fc 32 μM), or arachidonic acid (AA; Fc 0.5 mM) in patients treated with ASA and clopidogrel following PCI. High on-clopidogrel platelet reactivity (HPR) was defined as ADP-induced platelet aggregation ≥ 46 U. The manufacturer recommends performing the analysis within 30-180 min after blood draw. Patients were grouped according to the time from blood draw to MEA: 30-180 min, < 30 min, or > 180 min. Platelet function of 273 patients with coronary artery disease undergoing PCI with dual antiplatelet therapy was analyzed. The median age was 72 years (interquartile range, IQR 62-79) and 179 (66%) were male. Median ADP-, TRAP-, and AA-induced aggregation was 25 (IQR 18-36) U, 79 (IQR 63-96) U, and 12 (IQR 7-18) U, respectively. For those analyzed within 30-180 min from blood draw, no significant correlation of time from blood draw to MEA was observed 1) ADP (r = - 0.04, p = 0.51); 2) TRAP (r = - 0.06, p = 0.32); 3) AA (r = - 0.03, p = 0.67). In patients undergoing percutaneous coronary intervention and treated with dual antiplatelet therapy, the time from blood draw to multiple electrode aggregometry does not correlate with ADP- induced aggregation when the measurement occurred within the recommended time interval of 30-180 min after blood draw.


Strenuous exercise activates growth factors and chemokines over-expression in human serum of top-level triathlon athletes during a competitive season.
Regular exercise offers protection against all-cause mortality, primarily by protection against atherosclerosis and insulin resistance. There is evidence that physical training is effective as a treatment in patients with chronic heart diseases and type 2 diabetes. With excessive repetition of the training stimulus, local inflammation can generate a systemic inflammatory response. Cytokines play an important role in these processes. Our data confirm that cytokines that are considered to induce systemic bioactivity following exercise are not alone, but also growth factors and chemokines, which are secreted in exercise without the involvement of traditional proinflammatory cytokines, could be potent angiogenic factors.


Timing and outcomes of testicular torsion during the COVID-19 crisis.
During the COVID-19 crisis, there has been widespread reporting that non-COVID-19-related medical care has been delayed, even for emergent conditions. Testicular torsion is an emergent condition with higher risk of testicular loss with longer ischemic times. We sought to investigate whether patients with testicular torsion had longer time from symptom onset to initial presentation, longer total ischemic time, and higher rate of orchiectomy during the pandemic. Using billing data, we identified all patients age >1yo seen in our hospital from 1/1/2018 through 5/31/2020 who underwent emergent scrotal exploration for confirmed testicular torsion, comparing the COVID-19 crisis (3/1/2020-5/31/20) to the pre-COVID-19 period (1/1/2018-2/29/20). The primary outcome was time from symptom onset to initial presentation and secondary outcomes were ischemic time (time from symptom onset to entry of the OR) and orchiectomy rate. Parameters were compared with Mann-Whitney U and Fisher's exact tests; Poisson regression compared rates of torsion. Of 94 total cases, 77 occurred during the pre-COVID-19 period and 17 during the COVID-19 crisis. Median time from symptom onset to initial presentation was not significantly different (2.4 h [IQR 1.1 h-38.9] during COVID-19 vs. 5.6 h [IQR 1.6-16.9] during pre-COVID-19 period, p = 0.476). Time to presentation was >12 h in 5/17 patients (29%) during COVID-19 and 24/77 patients (31%) during pre-COVID-19 period (p = 1.00). Median ischemic time during COVID-19 was 7.5 h (IQR 4.7 h-45.5 h) compared to 9.4 h (IQR 5.4 h-22.5 h) during pre-COVID-19 period (p = 0.694). Incidence of orchiectomy in our center was 29% (5/17) during COVID-19 and 17% (13/77) during pre-COVID-19 period (p = 0.397). About half of patients were seen initially at outside facilities prior to arrival (47% [8/17] during COVID-19 vs. 49% [38/77] during pre-COVID-19 period, p = 1.00). The number of torsion case presentations per week to our facility increased from 0.7 cases/week in the pre-COVID-19 period to 1.3 cases/week during COVID-19 (p = 0.015); when comparing only the March 1 to May 31 calendar period, there were 0.6 cases/week during the pre-COVID-19 period and 1.3 cases/week during COVID-19 (p = 0.021). Time to presentation, ischemic times, and orchiectomy rates for testicular torsion at our center were not significantly different during the COVID-19 period compared to the preceding 2 year period. The number of torsion case per week presenting to our facility increased significantly.


A novel profuse color card for convenient visual determination of iodide in human urine based on catalytic oxidation reaction.
In this work, we reported a novel and convenient profuse color card for naked eye determination of iodide (I-) in urine using chromogenic substrate 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). I- catalyzed the oxidation of ABTS by peroxyacetic acid causing ABTS to yield cyan product ABTS+ with a new absorption peak at 730 nm. The addition of rose-red dye rhodamine B (RhB) changes the overall color of the solution from pink to purple and finally to blue, which makes the solution multicolor and easy to distinguish. A good linear relationship for I- was obtained ranging from 10.0 to 500.0 μg/L with the detection limit of 9.2 μg/L. Importantly, the sensor can semi-quantitatively estimate the concentration of I- in human urine with naked eye through the standard color card and assess the deficiency or excess of iodine in human body. The proposed profuse color card opens up a new colorimetric method for the rapid, simple and reliable determination of I- in clinic, and has promising applications in developing assay kit for the clinical diagnosis of I- in urine.


Novel CGRP receptor antagonists from central amide replacements causing a reversal of preferred chirality.
A previously utilized quinoline-for-N-phenylamide replacement strategy was employed against a central amide in a novel class of CGRP receptor antagonists. A unique and unexpected substitution pattern was ultimately required to maintain reasonable affinity for the CGRP receptor, while at the same time predicting acceptable heterocycle positioning for related analogs. Subsequently, specific quinoline and naphthyridine compounds were prepared which supported these structural predictions by displaying CGRP binding affinities in the 0.037-0.15 nM range.


Statistical methods for detecting activated regions in functional MRI of the brain.
Two statistical tests for detecting activated pixels in functional MRI (fMRI) data are presented. The first test (t-test) is the optimal solution to the problem of detecting a known activation signal in Gaussian white noise. The results of this test are shown to be equivalent to the cross-correlation method that is widely used for activation detection in fMRI. The second test (F test) is the optimal solution when the measured data are modeled to consist of an unknown activation signal that lies in a known lower dimensional subspace of the measurement space with added Gaussian white noise. A model for the signal subspace based on a truncated trigonometric Fourier series is proposed for periodic activation-baseline imaging paradigms. The advantage of the second method is that it does not assume any information about the shape or delay of the activation signal, except that it is periodic with the same period as the activation-baseline pattern. The two models are applied to experimental echo-planar fMRI data sets and the results are compared.


Electron immunocytochemical localization of enkephalin-like material in catecholamine-containing cells of the carotid body, the adrenal medulla, and in pheochromocytomas of man and other mammals.
Enkephalin-like immunoreactivity has been localized to electron-dense secretory granules of cat and piglet carotid bodies and adrenal medullae, horse adrenal medulla, and also to human adrenal medulla and pheochromocytomas using a gold-labeled antibody technique performed at the electron microscopic level. The same granules were also demonstrated to exhibit dopamine-beta-hydroxylase-like immunoreactivity, which suggests a granular colocalization of amines and peptides in catecholamine-storing cells.


Period versus cohort modeling of up-to-date cancer survival.
Recently, 2 modeling strategies have been proposed and shown to be useful to increase precision of up-to-date cancer survival estimates and to predict cancer patient survival: modeled period analysis and modeled cohort analysis. We aimed to compare the performance of both types of modeling for providing up-to-date and precise cancer survival estimates. Data from the nationwide Finnish Cancer Registry were used to assess how well both approaches would have been able to predict 5-year relative survival of concurrently diagnosed patients if they had been applied for that purpose throughout the past decades. Analyses were carried out for 20 common forms of cancer. For each cancer, 5-year relative survival was modeled with either approach for each single calendar year from 1962 to 1997. Mean differences and mean squared differences from 5-year relative survival later observed for patients diagnosed in the 5-year period around those calendar years were calculated. Survival estimates obtained by period modeling had much lower standard errors than those obtained by cohort modeling. Furthermore, for a clear majority of cancers, period modeling on average also provided better prediction of 5-year relative survival than cohort modeling. We conclude that, although both modeling strategies have their merits and specific indications, period modeling of survival has distinct advantages for up-to-date and precise estimation of cancer survival in population-based cancer survival studies.


Comparative proteomic analysis of engineered Saccharomyces cerevisiae with enhanced free fatty acid accumulation.
The engineered Saccharomyces cerevisiae strain △faa1△faa4 [Acot5s] was demonstrated to accumulate more free fatty acids (FFA) previously. Here, comparative proteomic analysis was performed to get a global overview of metabolic regulation in the strain. Over 500 proteins were identified, and 82 of those proteins were found to change significantly in the engineered strains. Proteins involved in glycolysis, acetate metabolism, fatty acid synthesis, TCA cycle, glyoxylate cycle, the pentose phosphate pathway, respiration, transportation, and stress response were found to be upregulated in △faa1△faa4 [Acot5s] as compared to the wild type. On the other hand, proteins involved in glycerol, ethanol, ergosterol, and cell wall synthesis were downregulated. Taken together with our metabolite analysis, our results showed that the disruption of Faa1 and Faa4 and expression of Acot5s in the engineered strain △faa1△faa4 [Acot5s] not only relieved the feedback inhibition of fatty acyl-CoAs on fatty acid synthesis, but also caused a major metabolic rearrangement. The rearrangement redirected carbon flux toward the pathways which generate the essential substrates and cofactors for fatty acid synthesis, such as acetyl-CoA, ATP, and NADPH. Therefore, our results help shed light on the mechanism for the increased production of fatty acids in the engineered strains, which is useful in providing information for future studies in biofuel production.


Evaluation of the genotoxicity of treated urban sludge in the Tradescantia micronucleus assay.
The sludge produced in sewage treatment plants can contain toxic substances. Among these, the genotoxic substances are of great concern. The present paper aimed at evaluating the genotoxicity of treated sludge samples collected at four different sewage treatment plants (STP) located in the State of São Paulo, Brazil using the Trad-MN assay. Another objective of the study was to compare the responses of the Clone #4430 with the Tradescantia pallida. Sludge samples mixed with reference soil in concentrations of 10, 25 and 50% (v/v) were tested in experiments with 3 months exposure in the field. Negative and positive controls (arsenic trioxide) were also tested with both plants. In Clone #4430 two sludge samples induced genotoxicity while in T. pallida three were positive, although no clear dose-response were observed for both plants. Results with the negative and positive controls suggest that T. pallida presented similar results when compared to the Clone #4430. The protocol using plants chronically exposed to sludge mixed with soil seems to be a promising tool to assess the genotoxicity of sludge although time consuming.


Influence of immobilisation of limbs in kittens on the morphology of the developing neuromuscular junctions.
Immobilisation of limbs in kittens, in which the neuromuscular apparatus is in active growing phase, affects the maturation of the end-plates, which appear smaller and pointed. Longer periods of immobilisation lead to a significant reduction in the surface area of the neuromuscular junctions which were seen to be "V" or "W" shaped.


AHNS endocrine surgery section consensus statement on nasopharyngolaryngoscopy and clinic reopening during COVID-19: How to get back to optimal safe care.
This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID-19 pandemic. The aim is to provide evidence-based recommendations defining the risks of COVID-19 in clinic, the importance of pre-visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.


Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients.
The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer. We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates. The effects of ASI were compared with those of surgery alone, and a pooled analysis was performed with the use of the data from random- or fixed-effect models. Twelve trials matched our inclusion criteria (n = 2993, including 1842 control subjects). The overall analysis showed a significant survival benefit [1-, 2-, 3-, 4-, 5-, 6- and 7-year overall survival (OS), P < 0.05; 10-year OS, P < 0.001] in favor of ASI immunotherapy combined with surgery, but there was not an improvement in the 8- or 9-year OS (P > 0.05). The disease-free survival (DFS) rate was improved after the combination of ASI immunotherapy (2-, 3-, 5- and 10-year DFS, P < 0.05), but no significant improvement was noted for the 1-, 4-, 6-, 7-, 8- or 9-year DFS (P > 0.05). In addition, the disease-specific survival (DSS) was improved at some time points after the combination of ASI immunotherapy and surgery (2-, 3-, 4-, 5- and 6-year DSS, P < 0.05, but not the 1-, 7-, 8- or 9-year DSS, P > 0.05). An improved 2-, 3-, 4-, 5- and 6-year recurrence-free interval (RFI) (P < 0.05) was also observed in patients who received ASI therapy, but this was not observed for the 1-year RFI (P > 0.05). Furthermore, an analysis of the recurrence-free survival (RFS) showed that it was significantly increased in the ASI plus surgery group (1-, 2-, 3-, 4-, 5- and 6-year RFS, P < 0.001). The funnel plots showed that the analyses were relatively reliable and the publication bias was small. The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone.


Concentration of 18:1 and 16:1 transunsaturated fatty acids in the adipose body tissue of decedents dying of ischaemic heart disease compared with controls: analysis by gas liquid chromatography.
Proportions of "lower" 16:1 and 18:1 trans acids (TL) and "higher" C20 and C22 trans acids (TH) in samples of depot fat taken at postmortem examination from 136 people who had died of ischaemic heart disease (cases) and from those who had died of unrelated causes (controls) have been determined. Whereas mean percentages of TH are virtually identical for cases and controls, the mean value of TL was significantly higher for the case specimens. Although these lower trans acids are present in small amounts in ruminant-animal fat, they are more characteristic of commercially hydrogenated fats. We conclude, therefore, that the cases consumed on average a higher proportion of those hydrogenated fats rich in 16:1 trans and 18:1 trans acids and a lower proportion of ruminant fat than did the controls.


Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition.
Safinamide is a novel neuroprotectant combining sodium and calcium channel blocking properties with selective, reversible monoamine oxidase type B (MAO B) inhibition. Phase 1 studies have demonstrated that in healthy volunteers, the ED50 (a dose that inhibits enzyme activity by 50% in 50% of treated subjects) for MAO B inhibition is 87.5 microg/kg/day orally, and that no MAO A inhibition occurs after 10-mg/kg oral dosing. To assess the risk of inducing the "cheese effect," the effect of safinamide and placebo on the pressor response to tyramine was investigated in a group of healthy male volunteers. The study was an open, single-dose placebo-controlled trial with the 2 treatments in sequence. An increase of 30 mm Hg systolic blood pressure was obtained by intravenous tyramine administered by 0.5-mg incremental boluses injected at 15-minute intervals. The amount of tyramine necessary to achieve such a blood pressure increase was the same after the safinamide 2-mg/kg oral load compared with placebo. These results suggest that dietary restrictions for food with high tyramine content should not be required under safinamide treatment.


Effects of ethanol on lipids and atherosclerosis.
Moderate alcohol consumption is associated with an increase in plasma high density lipoprotein (HDL) cholesterol concentration and a decrease in low density lipoprotein (LDL) cholesterol concentration. Changes in the concentration and composition of lipoproteins are estimated to account for more than half of alcohol's protective effect for coronary heart disease. Alcohol intake also affects plasma proteins involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, and phospholipases. In addition, alcohol intake may result in acetaldehyde modification of apolipoproteins. Furthermore, "abnormal" lipids, phosphatidylethanol and fatty acid ethyl esters are formed in the presence of ethanol and are associated with lipoproteins in plasma. Ethanol and ethanol-induced modifications of lipids may modulate the effects of lipoproteins on the cells in the arterial wall. The molecular mechanisms involved in these processes are complex, requiring further study to better understand the specific effects of ethanol in the pathogenesis of atherosclerosis. This review discusses the effects of ethanol on lipoproteins and lipoprotein metabolism, as well as the novel effects of lipoproteins on vascular wall cells.


Comprehensive plasma metabolites profiling reveals phosphatidylcholine species as potential predictors for cardiac resynchronization therapy response.
This study aimed to identify the plasma metabolite fingerprint in patients with heart failure and to develop a prediction tool based on differential metabolites for predicting the response to cardiac resynchronization therapy (CRT). We prospectively recruited 32 healthy individuals and 42 consecutive patients with HF who underwent CRT between January 2018 and January 2019. Peripheral venous blood samples, clinical data, and echocardiographic signatures were collected before CRT implantation. Liquid chromatography-mass spectrometry was used to perform untargeted metabolites profiling for peripheral plasma under ESI+ and ESI- modes. After 6 month follow-up, patients were categorized as CRT responders or non-responders based on the alterations of echocardiographic characteristics. Compared with healthy individuals, patients with HF had distinct metabolomic profiles under both ESI+ and ESI- modes, featuring increased free fatty acids, carnitine, β-hydroxybutyrate, and dysregulated lipids with heterogeneous alterations such as phosphatidylcholines (PCs) and sphingomyelins. Disparities of baseline metabolomics profile were observed between CRT responders and non-responders under ESI+ mode but not under ESI- mode. Further metabolites analysis revealed that a group of 20 PCs metabolites under ESI+ mode were major contributors to the distinct profiles between the two groups. We utilized LASSO regression model and identified a panel of four PCs metabolites [including PC (20:0/18:4), PC (20:4/20:0), PC 40:4, and PC (20:4/18:0)] as major predictors for CRT response prediction. Among our whole population (n = 42), receive operating characteristics analysis revealed that the four PCs-based model could nicely discriminate the CRT responders from non-responders (area under the curve = 0.906) with a sensitivity of 83.3% and a specificity of 90.0%. Cross-validation analysis also showed a satisfactory and robust performance of the model with the area under the curve of 0.910 in the training dataset and 0.880 in the testing dataset. Patients with HF held significantly altered plasma metabolomics profile compared with the healthy individuals. Within the HF group, the non-responders had a distinct plasma metabolomics profile in contrast to the responders to CRT, which was characterized by increased PCs species. A novel predictive model incorporating four PCs metabolites performed well in identifying CRT non-responders. These four PCs might severe as potential biomarkers for predicting CRT response. Further validations are needed in multi-centre studies with larger external cohorts.


Temporal fluctuations in vigilance and neural networks after sleep deprivation.
Vigilance instability in the sleep-deprived state was deemed to result from the imbalance in thalamic-FPN-DMN circuits (FPN: frontoparietal network; DMN: default mode network), but the behavioural correlation of this neural hypothesis is still unclear. To address this issue, we applied dynamic functional connectivity (DFC) analysis on the task-based fMRI data and detected high arousal state (HAS) and low arousal state (LAS). Relative to HAS, LAS demonstrated higher positive connectivity within task-positive networks (TPN), attenuated TPN-DMN anti-correlation, and greater anti-correlation between cerebral and subcortico-cerebellar networks. Critically, DFC differences between HAS and LAS were correlated with the ongoing vigilance performance in the sleep-deprived state. The current findings confirmed a direct link between vigilance instability and DFC in the thalamic-FPN-DMN circuits. In particular, we postulated that the integration within task-related system and segregation between task-related system and the subcortico-cerebellar system might be the critical neural markers underlying vigilance instability in the sleep-deprived state.


A method to detect 2-keto-3-deoxyoctanat and related compounds on pherograms and chromatograms.
A variation of the thiobarbituric acid spray reagent to detect 2-keto-3-deoxyoctanat (KDO), KDO derivatives, 2-deoxysugars, and N-acetylneuraminic acid on pherograms and chromatograms is described. Using all reagents in organic solvents and developing the color at room temperature, accurate locations of the spots without spreading and a low background stain are achieved.


Differential Gene Expression Profiles Involved in the Inflammations Due to COVID-19 and Inflammatory Bowel Diseases and the Investigation of Predictive Biomarkers.
Gastrointestinal manifestations in COVID-19 were attributed to 74-86% of the hospitalised patients due to severe or prolonged pathogenesis. Though it is a respiratory disease, the impact it elicits on the gastrointestinal tract and brain are intense. Inflammatory bowel disease including Crohn's disease and ulcerative colitis are idiopathic inflammatory disorders of the gastrointestinal tract. The intrinsic mechanisms involved in gut inflammations due to a respiratory viral disease can be deciphered when the gene expression profiles of COVID-19 and IBD are compared. The current study utilises an integrated bioinformatics approach to unravel them. The publicly available gene expression profiles of colon transcriptomes infected with COVID-19, Crohn's disease and Ulcerative colitis were retrieved, integrated and analysed for the identification of differentially expressed genes. The inter-relational analysis along with gene annotation and pathway enrichment detailed the functional and metabolic pathways of the genes during normal and diseased conditions. The protein-protein interactions deduced from the STRING database and the identified hub genes predicted potential biomarker candidates for COVID-19, Crohn's disease and ulcerative colitis. The inflammatory response pathways were upregulated and enrichment of chemokine signalling, altered lipid metabolism, coagulation and complement cascades were seen in all three conditions along with impaired transport mechanisms. CXCL11, MMP10, and CFB are predicted to be overexpressed biomarkers, whilst GUCA2A, SLC13A2, CEACAM, and IGSF9 as downregulated novel biomarker candidates for colon inflammations. The three miRNAs hsa-miR-16-5p, hsa-miR-21-5p, and hsa-miR-27b-5p exhibited significant interactions with the upregulated hub genes and four long non-coding RNAs NEAT1, KCNQ1OT1, and LINC00852 capable of regulating miRNA were also predicted. This study offers significant information on the underlying molecular mechanisms of inflammatory bowel disease with identification of potential biomarkers.


Exposure to indoor and outdoor air pollution in schools in Africa: Current status, knowledge gaps, and a call to action.
Chronic exposure to indoor and outdoor air pollution is linked to adverse human health impacts worldwide, and in children, these include increased respiratory symptoms, reduced cognitive and academic performance, and absences from school. African children are exposed to high levels of air pollution from aging diesel and gasoline second-hand vehicles, dusty roads, trash burning, and solid-fuel combustion for cooking. There is a need for more empirical evidence on the impact of air pollutants on schoolchildren in most countries of Africa. Therefore, we conducted a scoping review on schoolchildren's exposure to indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 μm and PM10 (particulate matter with an aerodynamic diameter less than 10 μm) in Africa. Following PRISMA guidelines, our search strategy yielded 2975 records, of which eight peer-reviewed articles met our selection criteria and were considered in the final analysis. We also analyzed satellite data on PM2.5 and PM10 levels in five African regions from 1990 to 2019 and compared schoolchildren's exposure to PM2.5 and PM10 levels in Africa with available data from the rest of the world. The findings showed that schoolchildren in Africa are frequently exposed to PM2.5 and PM10 levels exceeding the recommended World Health Organization air quality guidelines. We conclude with a list of recommendations and strategies to reduce air pollution exposure in African schools. Education can help to produce citizens who are literate in environmental science and policy. More air quality measurements in schools and intervention studies are needed to protect schoolchildren's health and reduce exposure to air pollution in classrooms across Africa.


Improving the quality of long-term care services in workforce dimension: expert views from Australia and South Korea.
The long-term care workforce is an essential factor in the provision of qualified long-term care services. Identifying workforce issues can help developing countries in East Asia and the Pacific prepare for the increase in the older population. Their experiences can be used as lessons for other countries. This study aimed to identify the workforce issues that should be addressed in order to provide high-quality long-term care services for older adults. In-depth interviews and content analysis were conducted with a purposive sample of long-term care experts. There were eight participants from Australia and 14 from South Korea. The participants were questioned on important workforce issues to improve the quality of long-term care services. These were open-ended questions that comprised ideas derived from the literature. Major themes were systematically and comprehensively classified and coded to examine recurring comments and themes. The issues in the two countries were very similar: labor shortages, inadequate working conditions, insufficient career and staff training, and the need of counselors or consultants for finding proper services. There were also differences in terms of competency of the service operators and their corresponding multicultural competency. Providing high-quality long-term care service requires multipronged approaches to workforce capacity and work environment. An adequate and competent workforce should be established to match the service needs of the older population. To improve quality, better working conditions and improved motivation to work in care for older people should be considered. Concurrently, each country would need a workforce strategy tailored to different conditions and environments. This should include policies to induce an influx into the workforce.


The paradoxical effects of suppressing anxious thoughts during imminent threat.
In line with the ironic processing theory of Wegner (Psychol. Rev. 101 (1994) 34), it is often argued that the suppression of anxiety-related thoughts results in a paradoxical increase of anxiety and thought intrusions, both after and during the thought suppression. In a sample of undergraduate students (14 men, 18 women), we investigated the effects of suppressing anxious thoughts about an imminent painful electrocutaneous stimulus. During thought suppression, self-reported anxiety and frequency of anxious thoughts did not increase, and duration of anxious thoughts decreased. After thought suppression, participants experienced an increase in self-reported anxiety and the frequency of anxious thoughts. There was no effect upon thought duration. The results support the idea that suppression of anxiety-related thoughts may result in a paradoxical increase in anxiety, and may cause and/or maintain anxiety problems.


Update of recent clinical trials in heart failure and myocardial infarction.
There are currently many on-going clinical trials assessing therapies for the treatment of patients with heart failure. The purpose of this series of papers is to present concise summaries of current randomised trials in the field of heart failure and myocardial infarction (MI). Data from large double-blind, placebo-controlled trials, which are on-going or have only recently been published, are given in a format allowing easy comparison. Where appropriate, data from smaller studies are included. Major studies which are examined in this issue include CIBIS II, MERIT-HF, RESOLVD, SPICE, VEST, MACH-1, ATLAS, RALES, CIDS and CASH. These trials assess the efficacy and safety of beta-blocker, angiotensin-II-receptor blocker, positive inotropic agent, calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor, aldosterone receptor blocker, and antiarrhythmic interventions in the treatment of heart failure. The presentation of data from these on-going trials should allow an up-to-date assessment, by physicians, of the most appropriate and effective treatment for patients with heart failure. It is evident that some therapies may play no further role in the treatment of heart failure, due to the increased risk of mortality associated with their administration, whilst others may convey significant benefits.


Heart rate and blood pressure biofeedback: II. A review and integration of recent theoretical models.
The theoretical models put forth separately by Bremer, Lang, and Schwartz to account for the data on biofeedback and cardiovascular responses are summarized and evaluated in light of recent empirical studies. Although each model makes some use of the idea that learning to control heart rate, particularly heart rate acceleration, is like motor skills learning, each model also emphasizes different sets of factors or variable. An attempted integration of these three models is presented.


Added value of combined acromiohumeral distance and critical shoulder angle measurements on conventional radiographs for the prediction of rotator cuff pathology.
To investigate the role of acromiohumeral distance (AHD) and critical shoulder angle (CSA) measurements from conventional radiographs (CR) in isolation and combined (prognostic index PIAHD-CSA) as predictors of full thickness rotator cuff tendon tears (RCT) and critical fatty degeneration (CFD; i.e. as much fat as muscle). In this retrospective study AHD and CSA were measured in 127 CR. MR arthrograms served as reference standard and were screened for RCT and CFD. Statistical analysis for inter-reader agreement, Spearman's rank correlation, linear stepwise regression and logistic regression for AHD and CSA with ROC analyses including PIAHD-CSA were performed. In 90 subjects (17 females, mean age 36.1 ± 14.1) no RCT were found on MR imaging and served as control group. In 37 patients (13 females, mean age 58.7 ± 13.2) ≥ one RCT was found. Inter-reader agreements rated between к = 0.42-0.82 for categorical and 0.91-0.96 for continuous variables. No significant correlation of AHD and CSA with either age or sex was seen (p = 0.28 and p = 0.74, respectively). Case group had significantly smaller mean AHD (8.7 ± 3.2 vs. 10.8 ± 2.2 mm; p < 0.001) and larger mean CSA (36.5 ± 4.5° vs. 33.1 ± 4.0°; p < 0.001). PIAHD-CSA increased diagnostic performance for prediction of RCT and CFD (AUC = 0.78 and 0.71), compared to isolated AHD (0.74 and 0.71) and CSA (0.71 and 0.66). AHD and CSA do not depend on age or sex but differ significantly between healthy and pathologic rotator cuffs. A decreased AHD is most influenced by infraspinatus muscle atrophy and fatty degeneration. Combined PIAHD-CSA increases diagnostic performance for predicting RCT and CFD.


The operative treatment of sacro-iliac subluxation and disruption of the symphysis pubis.
A method of internal fixation of the disrupted symphysis publis is discribed which uses readily available AO plates and tools. Patients can be mobilized at 3 days and discharged within 2 weeks. This method of treatment represents a considerable saving in nursing time and a great improvement for the patient, who is usually free from pain after 1 week.


Investigating the computational power of spiking neurons with non-standard behaviors.
Spiking neural networks have been called the third generation of neural networks. Their main difference with respect to the previous two generations is the use of realistic neuron models. Their computational power has been well studied with respect to threshold gates and sigmoidal neurons. However, biologically realistic models of spiking neurons can produce behaviors that can be computationally relevant, but their power has not been assessed in the same way. This paper studies the computational power of neurons with different behaviors based on the previous analyses conducted by Maass and Schmitt. The studied behaviors are rebound spiking, resonance and bursting. The results of the analysis are presented. A theoretical motivation for this study is presented and a discussion is done on the possible implications of the findings for using networks of spiking neurons for performing computations.


Roux-en-Y Gastric Bypass as Conversion Procedure of Failed Gastric Banding: Short-Term Outcomes of 1295 Patients in One Single Center.
Laparoscopic adjustable gastric band (LAGB) has high technical and weight loss failure rates. We evaluate here the 1-year morbidity, mortality, and weight loss of laparoscopic Roux-en-Y-gastric bypass (LRYGB) as a feasible conversion strategy. Patients with a failed primary LAGB who underwent LRYGB from July 2004 to December 2019 were selected from an electronic database at our center. Patients had a conversion to LRYGB at the same time (one-stage approach) or with a minimum of 3 months in between (two-stage approach). Primary outcomes included 30-day morbidity and mortality. Secondary outcomes were body mass index (BMI), percent excess weight loss (%EWL), and percent excess BMI lost (%EBMIL) at 1 year postoperatively. A total of 1295 patients underwent a conversion from LAGB to LRYGB at our center: 1167 patients (90.1%) in one stage and 128 patients (9.9%) in two stages. There was no mortality. An early (30-day) postoperative complication occurred in 93 patients (7.2%), with no significant difference found between groups. Hemorrhage was the most common complication in 39 patients (3.0%), and the reoperation was required in 19 patients (1.4%). At 1 year postoperatively, the mean BMI was 28.0 kg/m2, the mean %EWL 72.8%, and the mean %EBMIL 87.0%. No statistically significant difference was found between the groups. Conversion to LRYGB can be considered as a safe and effective option with low complication rate and good weight loss outcomes at 1 year. One-stage conversion provides the same early outcome as two-step surgery with a competent surgeon.


Growth of Cyanobacterium aponinum influenced by increasing salt concentrations and temperature.
The increasing requirement of food neutral biofuels demands the detection of alternative sources. The use of non-arable land and waste water streams is widely discussed in this regard. A Cyanobacterium was isolated on the area of a possible algae production side near a water treatment plant in the arid desert region al-Wusta. It was identified as Cyanobacterium aponinum PB1 and is a possible lipid source. To determine its suitability of a production process using this organism, a set of laboratory experiments were performed. Its growth behavior was examined in regard to high temperatures and increasing NaCl concentrations. A productivity of 0.1 g L-1 per day was measured at an alga density below 0.75 g L-1. C. aponinum PB1 showed no sign of altered growth behavior in media containing 70 g L-1 NaCl or less. Detection of a negative effect of NaCl on the growth using Pulse-Amplitude-Modulation chlorophyll fluorescence analysis was not more sensitive than optical density measurement.