An Interprofessional Simulation-Based Orientation Program for Transitioning Novice Nurses to Critical Care Roles in the Emergency Department: Pilot Implementation and Evaluation.
The emergency department (ED) relies on high-functioning teams to deliver consistent and safe patient care. Experts recommend that both emergency physicians and ED nurses participate in team training. However, there are currently no nationally accepted curricula for either profession to embed this training in their professional development, particularly for health workers who are novice or transitioning into critical care roles. An interprofessional educator team designed and embedded a series of simulation scenarios within a novel orientation program for novice nurses transitioning to critical care roles in the ED to teach clinical and teamwork skills for conjoint groups of resident physician and novice nurse learners. The team created four interprofessional simulations to represent the acuity and breadth of patient populations in the ED critical care bays. To date, the team has conducted 24 two-week orientation sessions for 48 nurses and 51 resident physicians. Overall mean scores for the Debriefing Assessment for Simulation in Healthcare (DASH) instrument from nursing participants in the first 18 sessions were high. Qualitative evaluation data from both nurses and physicians demonstrated a positive impact of the simulations and provided insight into respective roles, identities, and priorities across professions. Participant feedback led to iterative steps in refinement of the simulations, including adjustments in debriefings and logistics of the orientation program. A team-based interprofessional simulation program was found to be feasible and acceptable for practicing novice physicians and nurses as part of a nursing critical care orientation program in the ED. Future work will assess the program's long-term impact on teamwork and safety in the actual clinical environment.


Microglial derived nitric oxide decreases serotonin content in rat basophilic leukemia (RBL-2H3) cells.
Nitric oxide (NO) and serotonin (5-hydroxytryptamine; 5-HT) are important neuromodulators that are involved in a myriad of biochemical reactions. In this work, we describe a novel model co-culture system to study the interactions between NO and 5-HT. NO derived from cytokine stimulated Bv2 microglial cells depleted 5-HT from RBL-2H3 cells. Reduction of 5-HT content by NO derived from the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was concentration-dependent, independent of intracellular Ca(2+) and inhibited by reduced glutathione (GSH). Collectively, these data indicate that this cell co-culture system is a viable model to study the mechanisms of interaction between nitrergic and serotonergic pathways.


Endogenous adenosine inhibits excitatory transmission in the rat olfactory cortex slice.
Excitatory neurotransmission in the rat olfactory cortex slice has been monitored by measuring the amplitude of the N-wave surface field potential evoked by stimulation of the lateral olfactory tract. Application of exogenous adenosine or aspartate depressed the N-wave amplitude and evoked synthesis of cyclic AMP. These effects were partially antagonized by theophylline and the reduction of amplitude of the N-wave was potentiated by dipyridamole. When the olfactory tract slice was stimulated, dipyridamole alone reduced the amplitude of the N-wave and increased levels of cyclic AMP, both effects being antagonized by theophylline. Exogenous adenosine significantly attenuated the K+-evoked release of [3H]D-aspartate by a mechanism insensitive to either theophylline or dipyridamole. It is concluded that synaptic activation of the olfactory cortex releases adenosine, possibly as the result of the actions of the transmitter candidate of the olfactory tract, aspartate, and that this causes sufficient adenosine to accumulate to depress excitatory transmission and elevate tissue levels of cyclic AMP although there is no positive evidence that these two effects are directly related.


Anorexia, functional capacity, and clinical outcome in patients with chronic heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).
We aimed to assess determinants of anorexia, that is loss of appetite in patients with heart failure (HF) and aimed to further elucidate the association between anorexia, functional capacity, and outcomes in affected patients. We assessed anorexia status among 166 patients with HF (25 female, 66 ± 12 years) who participated in the Studies Investigating Co-morbidities Aggravating HF. Anorexia was assessed by a 6-point Likert scale (ranging from 0 to 5), wherein values ≥1 indicate anorexia. Functional capacity was assessed as peak oxygen uptake (peak VO2 ), 6 min walk test, and short physical performance battery test. A total of 57 patients (34%) reported any anorexia, and these patients showed lower values of peak VO2 , 6 min walk distance, and short physical performance battery score (all P < 0.05). Using multivariate analysis adjusting for clinically important factors, only high-sensitivity C-reactive protein [odds ratio (OR) 1.24, P = 0.04], use of loop diuretics (OR 5.76, P = 0.03), and the presence of cachexia (OR 2.53, P = 0.04) remained independent predictors of anorexia. A total of 22 patients (13%) died during a mean follow-up of 22.5 ± 5.1 months. Kaplan-Meier curves for cumulative survival showed that those patients with anorexia presented higher mortality (Log-rank test P = 0.03). Inflammation, use of loop diuretics, and cachexia are associated with an increased likelihood of anorexia in patients with HF, and patients with anorexia showed impaired functional capacity and poor outcomes.


Expression of MEGAP mRNA during embryonic development.
Mental retardation (MR) affects up to two percent of the population and is usually accompanied by impaired learning and memory. MR is frequently associated with mutations of genes involved in Rho signal transduction cascades. Rho signal transduction pathways regulate axonal and dendritic growth during embryonic development and morphological adaptations of dendritic spines during synaptic plasticity in adult neurons. The MEGAP/SRGAP3 protein is part of the Rho signal transduction cascades. Mutation of MEGAP (Mental disorder associated GTPase-activating protein) gene is present in some patients who have MR, ataxia and monosomy for the distal portion of the short arm of chromosome 3. Here, we investigated the pattern of mouse MEGAP mRNA expression during embryonic development. Mouse embryos and brain sections from stage E10 to adults were analysed by in-situ hybridisation for MEGAP transcript in whole-mount and in brain sections. We demonstrate here robust expression of MEGAP mRNA in the whole central nervous system of E10 embryos. At E12, we also detected MEGAP in dorsal root ganglia. This pattern narrows in adult animals into an expression mainly in hippocampus and cortex. Our findings support the presumed role of MEGAP in Rho-associated MR.


Tooth agenesis in a Portuguese population.
The aim of this retrospective study was to evaluate the prevalence and pattern of hypodontia in the permanent dentition, including and excluding third molars, in a Portuguese sample. The study group comprised 2888 patients, observed between 2005 and 2009 at the Dentistry Clinic of the Instituto Superior de Ciências de Saúde-Norte (ISCSN, Portugal). The patients were examined for evidence of hypodontia and presence or absence of deciduous teeth in those presenting agenesis. The age range varied from 7 to 21 years. In order to study the absence of the third molar, subjects under 14 years were excluded. Statistical analysis was performed using SPSS(®). Excluding third molars, the prevalence of tooth agenesis was 6.1% for the Portuguese population. Tooth agenesis was found more frequently in females than in males, although this difference was not statistically significant (P>.05). The most commonly missing tooth was the mandibular second premolar, followed by maxillary lateral incisor, and maxillary second premolar. There was a significantly higher prevalence of missing third molars in the agenesis group than in the non-agenesis group. There was a correlation between second premolar and upper lateral agenesis with presence of their corresponding deciduous teeth. The prevalence of tooth agenesis was found to be 6.1% for this Portuguese population and there was a correlation between agenesis and presence of deciduous teeth and between agenesis and missing third molars.


Nicotinamide Mononucleotide and Melatonin Alleviate Aging-induced Cognitive Impairment via Modulation of Mitochondrial Function and Apoptosis in the Prefrontal Cortex and Hippocampus.
Given the fact that both melatonin and nicotinamide mononucleotide (NMN) act as pleiotropic agents in various age-related cognitive disorders, we aimed to investigate the effect of these compounds separately and together on the cognitive outcomes, mitochondrial function, and apoptosis in aged rats. Forty old and ten young (24 and 3 months old, respectively) male Wistar rats were randomly allocated into five groups: Young+Normal saline (NS), Aged+NS, Aged+Melatonin, Aged+NMN, and Aged+melatonin+NMN. Melatonin (10 mg/kg) and NMN (100 mg/kg) were administered, separately or in combination for 28 every other day in aged animals. The Barnes maze and novel object recognition test were used to assess spatial and episodic-like memories, respectively. Also, apoptosis and alterations in mitochondrial function including reactive oxygen species (ROS) and ATP levels as well as mitochondrial membrane potential were assessed in both prefrontal cortex (PFC) and hippocampus (HIP) regions. Behavioral results revealed that NMN and melatonin separately or in combination, alleviate aging-induced memory impairment. Moreover, agents' co-administration declined mitochondrial dysfunction and apoptotic cell count both in PFC and HIP regions. The agents separately or in combination (more potent) could induce neuroprotective effect and improve learning and memory in aged animals.


Lipidome-wide characterization of phosphatidylinositols and phosphatidylglycerols on CC location level.
Phosphatidylglycerol (PG) and phosphatidylinositol (PI) are two essential classes of glycerophospholipids (GPs), playing versatile roles such as signalling messengers and lipid-protein interaction ligands in cell. Although a majority of PG and PI molecular species contain unsaturated fatty acyl chain(s), conventional tandem mass spectrometry (MS/MS) methods cannot discern isomers different in carbon-carbon double bond (CC) locations. In this work, we paired phosphate methylation with acetone Paternò-Büchi (PB) reaction, aiming to provide a solution for sensitive and structurally informative analysis of these two important classes of GPs down to the location of CC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow was established. Offline methylated PG or PI mixtures were subjected to hydrophilic interaction chromatographic separation, online acetone PB reaction, and MS/MS via collision-induced dissociation (CID) for CC location determination in positive ion mode. This method was sensitive, offering limit of identification at 5 nM for both PG and PI standards down to CC locations. On molecular species level, 49 PI and 31 PG were identified from bovine liver, while 61 PIs were identified from human plasma. This workflow also enabled ratiometric comparisons of CC location isomers (C18:1 Δ9 vs. Δ11) of a series of PIs from type 2 diabetes (T2D) plasma to that of normal plasma samples. PI 16:0_18:1 and PI 18:0_18:1 were found to exhibit significant changes in CC isomeric ratios between T2D and normal plasma samples. The above results demonstrate that the developed LC-PB-MS/MS workflow is applicable to different classes of lipids and compatible with other established lipid derivatization methods to achieve comprehensive lipid analysis.


Reversible emetine-induced myopathy with ECG abnormalities: a toxic myopathy.
A young anorexic woman is described with a history of progressive muscle weakness following chronic ingestion of syrup of ipecac that was used in an attempt at weight control. Electrocardiogram (ECG) showed T-wave inversion in all leads and prolongation of the Q-T interval. Electromyography was abnormal. Muscle biopsy revealed a randomized, generalized, predominantly type-2 fibre atrophy and structural alterations in oxidative enzyme stains, such as targetoid and moth-eaten fibres. A few necrotic cells were actively phagocytosed. Electron microscopy revealed severe sarcomeric abnormalities with Z-line streaming, myofibrillar disorganization and increased lysosomal activity. After discontinuation of ipecac syrup, the patient noted a gradual improvement in her condition. The ECG became normal. Emetine and related drug-induced myopathies are uncommon but are of experimental interest because of their effects on mitochondria and the light they shed on autophagic mechanisms in muscle.


Successful pregnancy following myomectomy for uterine smooth muscle tumor of uncertain malignant potential: A case report and review of the literature.
•STUMPs are rare smooth muscle tumors with an overall favorable prognosis.•Pregnancy is possible after diagnosis of STUMP treated with myomectomy•Management of patients desiring fertility with STUMPs requires a multidisciplinary approach.


Structural analysis of human apolipoprotein A-I variants. Amino acid substitutions are nonrandomly distributed throughout the apolipoprotein A-I primary structure.
In the course of an electrophoretic mutation screening program of 32,000 dried blood samples from newborns, 17 genetic variants of apolipoprotein A-I (apoA-I) were found and structurally analyzed. The following defects were identified by the combined use of high performance liquid chromatography, time-of-flight secondary ion mass spectrometry, and sequence analysis: Pro3----Arg (1 x), Pro4----Arg (1 x), Asp89----Glu (1 x), Lys107----0 (4 x), Lys107----Met (2 x), Glu139----Gly (2 x), Glu147----Val (1 x), Pro165----Arg (4 x), and Glu198----Lys (1 x). The distribution of point mutations in the apoA-I gene leading to these 9 and 11 other variants of apoA-I reported previously was statistically analyzed. Substitutions are overrepresented in the 10 amino-terminal amino acids (p less than 0.001, chi 2-test) and in residues 103-177 (p less than 0.025, chi 2-test) or residues 103-198 (p less than 0.05, chi 2-test), respectively. We further noted the following. (i) Prolines were substituted by arginine or histidine residues at a frequency much higher than expected on the basis of random nucleotide substitutions (5 out of 18 "electrically non-neutral" amino acid substitutions, p less than 0.001, chi 2-test). These substitutions are the result of transversions of cytosines contained within stretches of at least 5 consecutive cytosines in the apoA-I gene. The observed hypervariability of the apoA-I amino terminus, therefore, might be caused by a hot spot for mutation formed by the 7 subsequent cytosines in codons 3, 4, and 5. (ii) CpG dinucleotides were overrepresentatively affected by C----T transitions (5 out of 18 electrically nonneutral amino acid substitution, p less than 0.001, chi 2-test). The hypervariability of the apoA-I alpha-helical domain might therefore be caused by CpG dinucleotides predominantly occurring in codons 120-208 of apoA-I (82 out of 125). (iii) Comparison of mutation sites in the human apoA-I gene with sites of nonsynonymous substitutions revealed that amino acid substitutions found in human apoA-I were predominantly localized in areas that were little conserved during mammalian evolution. These regions may therefore represent areas of less structural constraint for the function of apoA-I.


In vitro characterization of lactic acid bacterial strains isolated from fermented foods with anti-inflammatory and dipeptidyl peptidase-IV inhibition potential.
Probiotics are known to stimulate, modulate, and regulate host immune response by regulating specific sets of genes and improve glucose homeostasis through regulating dipeptidyl peptidase (DPP-IV) activity, but the mechanism behind their protective role is not clearly understood. Therefore, the present study was designed to isolate indigenous lactic acid bacterial (LAB) strains from different fermented food samples, vegetables, and human infant feces exhibiting anti-inflammatory, antioxidant, and DPP-IV inhibitory activity. A total of thirty-six Gram-positive, catalase-negative, and rod-shaped bacteria were isolated and screened for their anti-inflammatory activity using lipopolysaccharide (LPS)-induced inflammation on the murine (RAW264.7) macrophages. Among all, sixteen strains exhibited more than 90% reduction in nitric oxide (NO) production by the LPS-treated RAW264.7 cells. Prioritized strains were characterized for their probiotic attributes as per the DBT-ICMR guidelines and showed desirable probiotic attributes in a species and strain-dependent manner. Accordingly, Lacticaseibacillus rhamnosus LAB3, Levilactobacillus brevis LAB20, Lactiplantibacillus plantarum LAB31, Pediococcus acidilactici LAB8, and Lactiplantibacillus plantarum LAB39 were prioritized. Furthermore, these strains when co-supplemented with LPS and treated on RAW264.7 cells inhibited the mitogen-activated protein kinases (MAPKs), i.e., p38 MAPK, ERK1/2, and SAPK/JNK, cyclooxygenase-2 (COX-2), relative to the LPS-alone-treated macrophages. LAB31 and LAB39 also showed 64 and 95% of DPP-IV inhibitory activity relative to the Lacticaseibacillus rhamnosus GG ATCC 53103, which was used as a reference strain in all the studies. Five prioritized strains ameliorated the LPS-induced inflammation by downregulating the JNK/MAPK pathway and could be employed as an alternative bio-therapeutic strategy in mitigating gut-associated inflammatory conditions. The potential mechanism of action of prioritized LAB strains in preventing the LPS-induced inflammation in RAW 264.7 macrophage cells.


Transport of the synthetic peptide DSIP through the blood-brain barrier in rabbit.
The synthetic delta sleep inducing peptide (DSIP) passes the blood-brain barrier, since i.v. injection in free moving rabbits (30 nmoles/kg) significantly increases the cortical delta activity and decreases the motor activity during 5 h.


Computer simulation of the conformational behavior of cholecystokinin fragments: conformational families of sulfated CCK8.
Display methods, such as principal component analysis, and clustering methods were applied to a sample of cholecystokinin, (sulfated CCK8) conformations obtained from a Monte Carlo simulation. It is shown that six families of conformations can entirely describe the sample. Each family represents a typical conformer. These theoretical models are in agreement with recent experimental results which stress the predominance of folded conformers in aqueous medium.


Does bacteriorhodopsin energize the membranes of animal mitochondria under light?
A suspension of freeze-thawed mitochondria mixed with purple membranes from Halobacteria was illuminated with visible light. It was found that the light exposure prevented inhibition of succinate oxidation. The illumination also led to a decrease in inhibition of the rate of ferricyanide reduction by rat liver mitochondria in the presence of succinate. Both phenomena are explained by the fact that oxalacetate inhibition of succinate dehydrogenase is prevented by light-induced energization of mitochondrial membranes due to the contact with purple membranes.


Factitious hyperinsulinemic hypoglycemia: confirmation of the diagnosis by a species-specific insulin radioimmunoassay.
Surreptitious self-administration of insulin is an important cause of hypoglycemia. A 28-year-old female hospital ward clerk presented with hypoglycemia associated with an elevated plasma insulin level and a low plasma C-peptide concentration. Factitious illness was denied by the patient until it was definitively proven by using a species-specific insulin radioimmunoassay that the type of insulin circulating at the time of hypoglycemia was of animal rather than of human origin. The differential diagnosis of hypoglycemia associated with hyperinsulinemia and the current laboratory methods which may be employed to distinguish between factitious hypoglycemia and endogenous hyperinsulinism are discussed.


The Menzies School of Health Research offers a new paradigm of cooperative research.
The Menzies School has addressed problems in Aboriginal and tropical health through research that requires cooperation between disciplines as well as improved communication and trust between researchers, Aboriginal people and the wider community.


Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus.
Fruiting bodies of Phellinus linteus were extracted with 70% ethanol at room temperature. The Phellinus linteus extract (PL) showed strong anti-angiogenic activity, which was detected using the chick embryo chorioallantoic membrane (CAM) assay. The in vitro antioxidant activities of PL were evaluated using two different bioassays. PL was comparable to Vitamin C in scavenging the stable free radical 1,1-diphenyl-2-picrylhyrazyl (DPPH). It also inhibited lipid peroxidation (LPO) in a concentration-dependent manner. These results suggest that antioxidant and anti-angiogenic activities of Phellinus linteus would be partly responsible for its anti-tumor effect.


Endoscopic balloon dilatation for benign fibrotic strictures after curative nonsurgical treatment for esophageal cancer.
Endoscopic balloon dilatation (EBD) is performed to treat strictures after esophagectomy. However, little is known about using EBD for benign strictures that occur after nonsurgical treatments for esophageal cancer such as chemoradiotherapy (CRT) or endoscopic mucosal resection (EMR). The aim of this study was to evaluate the safety and efficacy of EBD for benign strictures after nonsurgical treatment compared with those after surgery. We identified 823 patients with esophageal cancer who completed definitive treatments between 2004 and 2007. Of these patients, 122 were enrolled in our study, including 60 who had surgery and 62 who did not have surgery (32 CRT, 30 EMR). The indication criteria for EBD were complaint of dysphagia and the inability to pass a conventional endoscope due to benign stricture. We retrospectively analyzed the safety and efficacy of EBD, and the measured outcomes were treatment success rate, time to treatment success, and refractory stricture rate. Perforation occurred in 3 (0.3 %) of 1,077 EBD sessions, with no bleeding. Efficacy was evaluated in 110 of the 122 patients. While the treatment success rate was over 90 % in both the surgery and the nonsurgery group, there was a significant difference in the median time to treatment success between both groups (2.3 vs. 5.6 months, p = 0.02: log-rank test). There was a significant difference in the median time to treatment success between CRT and surgery groups (7.0 months, p = 0.01), with no significant difference in the EMR group (4.4 months, p = 0.85). A significant difference in the refractory stricture rate was evident between the nonsurgery group (75 %) and the surgery group (45 %, p < 0.01). EBD for stricture after nonsurgical treatment of esophageal cancer was safe and effective. However, patients with benign strictures after nonsurgical treatment required significantly longer time to recover from dysphasia compared to those after surgery.


The Special Medical Physics Consult Process for Reirradiation Patients.
To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process. An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined. The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines. As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.


The discovery of disability: a phenomenological study of unilateral neglect.
Clients with right brain damage and unilateral neglect often lack awareness of their disabilities. This study examined how 4 participants with neglect experienced, discovered, and handled their disabilities in the context of their everyday life. The 4 participants were interviewed five to seven times during their rehabilitation process. The data were collected and analyzed using the EPP (empirical, phenomenological, psychological) method. Findings revealed seven features that described a discovery process for the 4 participants. During this process, each participant began to discover and understand the consequences of her unilateral neglect in the performance of everyday tasks. This increased understanding was a prerequisite to being able to use compensatory strategies. By experiencing meaningful occupational situations, the participants gradually discovered and began to compensate for their disabilities in everyday life.


Depolarization-induced neurite outgrowth in PC12 cells requires permissive, low level NGF receptor stimulation and activation of calcium/calmodulin-dependent protein kinase.
Neuronal activity is required for normal neural development. Excessive activity can cause abnormal growth of neural processes and may contribute to formation of epileptic foci. Using PC12 cells, we investigated mechanisms by which depolarization regulates neurite growth. Depolarization with 45 mM KCl induced neurite outgrowth only if NGF receptors were partly activated by overexpression of p140trkA or by treatment with a low concentration of NGF that alone was insufficient to stimulate neurite formation. Depolarization-induced neurite growth was reduced by inhibitors of L-type Ca2+ channels, Ca2+/calmodulin-dependent protein (CaM) kinases II and IV, and transcription. These results identify a novel mechanism by which depolarizing stimuli synergize with subthreshold activation of NGF receptors to induce neurite growth through a Ca2+ and CaM kinase-dependent signal transduction pathway.


The electrocardiographic response to maximal treadmill exercise of asymptomatic men with left bundle branch block.
This study presents the results of maximal treadmill testing and coronary angiography in 31 asymptomatic USAF aircrewmen with acquired left bundle branch block. There were two subgroups: 26 men with normal coronary angiography and five men with significant angiographic coronary angiography and five men with significant angiographic coronary artery disease. The mean amount of maximal ST-segment depression induced by treadmill exercise was --0.5 mv. for both groups and the range in the normal subgroup was --0.3 to --1.0 mv. No significant differences were found between the groups. We concluded that apparently healthy, asymptomatic men with acquired left bundle branch block can have considerable ST-segment depression in response to maximal treadmill testing and that their ST-segment response cannot be used to make diagnostic decisions about them.


Photocrystallographic and spectroscopic studies of a model (N,N,O)-donor square-planar nickel(II) nitro complex: in search of high-conversion and stable photoswitchable materials.
A new, cheap, easy-to-synthesize and air-stable photoswitchable nickel(II) complex, QTNiNO2, is reported. The metal centre in QTNiNO2 is coordinated by a nitro group and a [2-methyl-8-amino-quinoline]-1-tetralone ligand. The compound crystallizes in the tetragonal space group I41/a with one complex molecule comprising the asymmetric unit, and the crystals are stable under ambient conditions. Irradiation of the solid-state form of QTNiNO2 with 530-660 nm LED light at 160 K converts the ambidentate nitro moiety fully to the nitrito linkage isomer which is stable up to around 230 K, as indicated by IR spectroscopy measurements. The structures of all species present in the examined crystals and their thermal stability were confirmed via X-ray multi-temperature and photocrystallographic experiments. The impact of temperature on the (photo)isomerization reaction taking place in a single crystal was additionally investigated. The experimental results are supported by computational analyses of crystal packing and intermolecular interactions that influence the isomerization process studied.


Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.
Glycogen synthase kinase-3 (GSK3) is a highly evolutionarily conserved serine/threonine protein kinase first identified as an enzyme that regulates glycogen synthase (GS) in response to insulin stimulation, which involves GSK3 regulation of glucose metabolism and energy homeostasis. Both isoforms of GSK3, GSK3α, and GSK3β, have been implicated in many biological and pathophysiological processes. The various functions of GSK3 are indicated by its widespread distribution in multiple cell types and tissues. The studies of GSK3 activity using animal models and the observed effects of GSK3-specific inhibitors provide more insights into the roles of GSK3 in regulating energy metabolism and homeostasis. The cross-talk between GSK3 and some important energy regulators and sensors and the regulation of GSK3 in mitochondrial activity and component function further highlight the molecular mechanisms in which GSK3 is involved to regulate the metabolic activity, beyond its classical regulatory effect on GS. In this review, we summarize the specific roles of GSK3 in energy metabolism regulation in tissues that are tightly associated with energy metabolism and the functions of GSK3 in the development of metabolic disorders. We also address the impacts of GSK3 on the regulation of mitochondrial function, activity and associated metabolic regulation. The application of GSK3 inhibitors in clinical tests will be highlighted too. Interactions between GSK3 and important energy regulators and GSK3-mediated responses to different stresses that are related to metabolism are described to provide a brief overview of previously less-appreciated biological functions of GSK3 in energy metabolism and associated diseases through its regulation of GS and other functions.


Effect of dimethylsphingosine on muscarinic M(3) receptor signalling in SH-SY5Y cells.
The sphingosine kinase inhibitor, dimethylsphingosine, is an important tool for investigating intracellular effects of the putative second messenger compound, sphingosine 1-phosphate. However, the specificity of action of dimethylsphingosine has not been fully investigated. In human SH-SY5Y neuroblastoma cells, dimethylsphingosine (30 microM), produced a 25-fold increase in the EC(50) for methacholine-induced Ca(2+) mobilisation, and reduced the maximum response by 57+/-5%, suggesting the involvement of sphingosine 1-phosphate production in the Ca(2+) signal. However, dimethylsphingosine also inhibited [3H]N-methylscopolamine binding to whole SH-SY5Y cells and reduced methacholine-induced phosphoinositide turnover. Thus, this compound must be used with caution when investigating the role of sphingosine kinase in G-protein coupled receptor-mediated Ca(2+) mobilisation responses.


Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase.
Treatment with catalase and SOD (superoxide dismutase) could diminish the damage due to oxygen free radical formation, but these enzymes are rapidly removed from circulation. The covalent attachment of monomethoxypolyethylene glycol (PEG) to catalase and SOD extended their plasma half-lives. Toxicity of PEG-catalase and PEG-SOD was evaluated in mice and rats prior to their use as free radical scavengers. Rodents used in acute, subacute, and subchronic toxicologic studies could tolerate large doses of PEG-catalase and PEG-SOD without developing toxic signs. The conjugates did not affect survival rate, appearance, behavior, food intake, blood chemistry, hematology, or urinalysis. In general, body weight gains, organ weights, and histomorphology were also unaffected. Massive doses of PEG-catalase caused slight weight loss, splenic hypertrophy, and generalized splenic stimulation in mice. Massive doses of PEG-SOD resulted in vacuolation in splenic macrophages in rats. PEG-catalase and PEG-SOD circulated for 3 days and 8 days, respectively, in mice following i.v. or i.m. administration.


Small strain deformation measurements of konjac glucomannan solutions and the influence of borate cross-linking.
The dynamic rheology of aqueous solutions of konjac glucomannan has been evaluated over a range of concentrations up to 2.35%, and the effect of borate cross-linking of such solutions evaluated in the range 0.02-40 mM borate. In preliminary work, conventional parallel plate geometries were employed and in situ cross-linking was investigated. For borate cross-linked samples a superior method, however, was found to be measurement of pre-formed cores of cross-linked polymer into which a four-bladed vane geometry was introduced. In order to compare with other associating polymer systems, rheological data were analysed by defining plateau moduli, corresponding relaxation times and zero shear viscosities and the scaling behaviour of these parameters with polymer and cross-linker concentrations was established. Maxwell fits and time-concentration superposition procedures were investigated. The rheological properties of the cross-linked polymer were shown to be the result of both increased network connectivity and retarded network dynamics.


Sonoluminescence from non-aqueous liquids.
Our understanding of the chemical effects of high-intensity ultrasonic irradiation of liquids is still quite limited. It is generally accepted that sonochemistry results from acoustic cavitation: the creation, growth, and implosive collapse of bubbles in ultrasonically irradiated liquids. The mechanism of sonoluminescence in aqueous systems has been a matter of some dispute; recent discussions have suggested at least three possible origins: black-body emission, chemiluminescence from radical recombination, and electric discharge. Few studies of non-aqueous sonoluminescence, however, have been conducted. We present here the first spectrally resolved sonoluminescence spectra from hydrocarbon and halocarbon liquids. These spectra originate unambiguously from excited-state molecules created during acoustic cavitation. These high-energy species probably result from the recombination of radical and atomic species generated during the high temperatures and pressures of cavitation.


Altered EEG lagged coherence during rest in obsessive-compulsive disorder.
Functional magnetic resonance imaging (fMRI) studies found alterations of functional connectivity in obsessive compulsive disorder (OCD). However, there is little knowledge about region of interest (ROI) based electroencephalogram (EEG) connectivity, i.e. lagged non-linear and linear coherence in OCD. Goal of this study was to compare these EEG measures during rest and at different vigilance stages between patients and healthy controls (HC). A 15 min resting-state EEG was recorded in 30 unmedicated patients and 30 matched HC. Intracortical lagged non-linear coherence of the main EEG-frequency bands within a set of frontal ROIs and within the default mode network (DMN) were computed and compared using intracortical exact low resolution electromagnetic tomography (eLORETA) software. Lagged non-linear but not linear coherence was significantly decreased for patients in comparison to HC for the beta 2 frequency between frontal brain areas but not within the DMN. When analysing separate EEG-vigilance stages, only high vigilance stages yielded decreased frontal phase synchronisation at beta and theta frequencies. The results underline an altered neuronal communication within frontal brain areas during rest in OCD. These findings encourage further research on connectivity measures as possible biomarkers for physiological homogeneous subgroups.


Early decompressive craniotomy in children with severe traumatic brain injury.
Decompressive craniectomy remains a controversial procedure in the treatment of raised intracranial pressure (ICP) associated with post-traumatic brain swelling. Although there are a number of studies in adults published in the literature on this topic, most commonly as a salvage procedure in the treatment of refractory raised ICP, there are few that investigate it primarily in children with head injuries. Our aim was to report the experience with decompressive craniotomy in children with severe traumatic brain injury (TBI) at the Red Cross Children's' hospital. This study reports five patients in whom decompressive craniectomy or craniotomy with duraplasty was used as an early, aggressive treatment of raised ICP causing secondary acute neurological deterioration after head injury. The rationale was to save the patient from acute cerebral herniation and to prevent exposure to a prolonged course of intracranial hypertension. All patients benefited from the procedure, demonstrating control of ICP, radiological improvement and neurological recovery. Long-term follow-up was available, with outcome assessed at a minimum of 14 months after injury. The early approach to the use of decompressive craniotomy in the treatment of severe traumatic brain injury (TBI) with secondary deterioration due to raised ICP is emphasised. A favourable outcome was achieved in all of the cases presented. The potential benefit of decompressive craniectomy/craniotomy in the management of children with severe TBI is discussed.


Factors associated with caregiver burden of adults with epilepsy in a middle-income country.
Despite the relevance of socio-economic background in burden of caregivers of persons with epilepsy (PWE), there is a dearth of knowledge about this topic in low-resource settings. Here we attempt to identify the extent of the burden in caregivers of adults with epilepsy in a middle-income country and the factors associated with it. In this cross-sectional study, we evaluated the level of burden with the Zarit Caregiver Burden Inventory. A comprehensive questionnaire was developed to assess the demographics of patients and caregivers. Epilepsy-related factors were obtained by interview and file review. Depressive, anxiety symptoms, and sleep quality were evaluated by Beck Depression Inventory, State and Trait Anxiety Inventory, and Pittsburgh Sleep Quality Index. Stigma was evaluated by the Stigma Scale of Epilepsy. The caregiver's burden was mild to moderate in our sample. The factors most strongly associated with the higher caregiver burden were age-onset of epilepsy, PWE years of schooling, needs for assistance in daily life, disabilities, and caregiver's bad-quality of sleep and higher depressive and anxiety symptoms. Caregivers of PWE deserve special attention regarding mental health and other health aspects, such as sleep quality.


Platelet-activating factor and its structural analogues in the earthworm Eisenia foetida.
The earthworm Eisenia foetida was shown to contain large amounts of ether-containing phospholipids such as alkylacylglycerophosphocholine (61.3% of choline glycerophospholipids) and alkenylacylglycerophosphoethanolamine (66.0% of ethanolamine glycerophospholipids). We also found a substantial amount of ether-containing PAF-like lipid in this animal, its level being increased after the animal is injured. We showed evidence that this PAF-like lipid consists of PAF and PAF analogues containing short chain fatty acids other than acetic acid. Notably, a propionic acid-containing species but not PAF itself, is the most predominant species in this animal. We also confirmed that the earthworms contain enzyme activities involved in the synthesis of PAF and short chain fatty acid-containing PAF analogues. Interestingly, the acetyltransferase activity in earthworms is resistant to high concentrations of the substrate lysophospholipid. Thus, both the structure of the PAF-like lipid and the properties of the enzymes involved in the PAF-like lipid metabolism in the earthworms are somewhat different from those in mammalian tissues.


Postoperative pain-related morbidity: video-assisted thoracic surgery versus thoracotomy.
One hundred thirty-eight consecutive, nonrandomized patients, with equivalent demographic and preoperative physiologic parameters, underwent either a video-assisted thoracic surgical (VATS) approach (n = 81) or a limited lateral thoracotomy (LLT) approach (n = 57) to accomplish pulmonary resection for peripheral lung lesions (< or = 3 cm in diameter). Wedge resection was done in 74 VATS patients and 19 LLT patients. Seven patients underwent VATS lobectomy and 38 patients had lobectomy performed through an LLT. Pain was quantitated by postoperative narcotic requirements, the need for intercostal/epidural analgesia, and patient perception of pain index scoring. Shoulder and pulmonary function (forced expiratory volume in 1 second) were measured preoperatively, 3 days postoperatively, and at 3 weeks of follow-up. Patients undergoing VATS experienced significantly less postoperative pain. No patients undergoing VATS required intercostal block/epidural analgesia; 31 LLT patients (54%) required this treatment for breakthrough pain (p = 0.001). Narcotic requirements were less (p = 0.05) among VATS patients, which correlated with lower perception of pain index after operation for VATS patients. Shoulder girdle strength was equally impaired at day 3, but function was more improved in VATS patients at 3 weeks (p = 0.01). Patients undergoing wedge resection alone by LLT had greater impairment in early (day 3) pulmonary function (forced expiratory volume in 1 second) (p = 0.002); this difference from VATS was not sustained at 3 weeks. Video-assisted thoracic surgery is associated with reduced pain, shoulder dysfunction, and early pulmonary impairment compared with LLT for select patients requiring pulmonary resection.


Effects of a 16-week recreational team handball intervention on aerobic performance and cardiometabolic fitness markers in postmenopausal women: A randomized controlled trial.
Postmenopausal women have an elevated risk of developing cardiovascular diseases, which can be counteracted by conventional exercise regimes or recreational football. Less is known about the impact of exercise programmes based on other team sports. Thus, we examined the effects of recreational team handball on aerobic performance, cardiorespiratory fitness and cardiometabolic health in untrained postmenopausal women. Sixty-seven participants (age 68 ± 6 years, stature 157 ± 6 cm, body mass 67 ± 10 kg, fat mass 37 ± 7%, VO2peak 25.2 ± 3.6 mL/min/kg, Yo-Yo intermittent endurance level 1 test performance (YYIE1) 230 ± 103 m) with no previous experience of team handball were randomly allocated to either a team handball (THG, n = 41) or a control (CG, n = 26) group. THG performed 2-3 60-min training sessions per week for 16 weeks. YYIE1 performance and cardiometabolic markers were evaluated at baseline and post-intervention. Average attendance during recreational team handball training was 1.9 ± 0.4 sessions per week, with mean heart rates of 76 ± 6%HRmax and 18 ± 9 min (44 ± 20% of total time) played at HR > 80%HRmax. A between-group effect was observed for YYIE1 performance, with a more pronounced improvement in aerobic exercise performance in THG compared to CG (70 ± 62 vs 15 ± 44%; p < 0.001). Within-group improvements (p < 0.05) were observed for THG with regard to VO2peak (7 ± 10%), incremental treadmill test time to exhaustion (TTE) (11 ± 14%), total cholesterol (-3 ± 9%) and low-density lipoprotein cholesterol (-2 ± 14%), with no significant changes in CG except an increase (p < 0.05) in TTE. Post-intervention values were higher for THG vs CG for YYIE1 performance (88%; 406 ± 216 vs 216 ± 75 m) and VO2peak (10%; 27.5 ± 3.8 vs 24.9 ± 3.6 mL/min/kg). Recreational team handball can be used to obtain moderate-to-vigorous aerobic intensities, and just 2 weekly 60-min team handball training sessions for 16 weeks can result in improvements in aerobic performance and in markers of cardiorespiratory fitness in postmenopausal women with no previous experience of the sport.


Glaucoma of the brain: a disease model for the study of transsynaptic neural degeneration.
The identification of mechanisms precipitating neuronal death and injury is an intense area of investigation requiring reliable models to assess the effects of neuroprotective agents. Most are suboptimal since the effects of initial damage are diffuse and may not be reproducible or easily quantifiable. The ideal laboratory model should have the ability to (a) clearly detect evidence of neuronal injury and recovery, (b) accurately measure morphologically the extent of these changes, and (c) provide functional evidence for damage and recovery. Glaucoma is a disease of visual neurons in the eye and brain. In the visual system, neuroanatomical pathways and retinotopic organization are exquisitely defined, functional modalities are highly characterized and can be dissected physiologically, visual input parameters can be modified, visual functional output can be readily tested and measured, changes in the eye and the visual brain can be directly visualized and imaged, and pathological and compensatory changes in brain centers of vision can be examined and measured specifically. For these reasons, the glaucoma disease model is ideal for the study of response and recovery to injury in the central nervous system due to anterograde and retrograde degeneration from the eye to the brain and the brain to the eye, respectively. The study of this glaucoma model of transsynaptic brain injury may be relevant to understanding more complex pathways and point to new strategies to prevent disease progression in other neurodegenerative diseases.


Pregnancies following pronuclear stage tubal transfer.
Pronuclear stage tubal transfer (PROST) is a technique that involves in vitro fertilization (IVF) of oocytes, followed by the transfer of pronuclear oocytes into the fallopian tubes. It has been developed for its prognostic value of confirming fertilization in couples with oligospermia or asthenospermia and enabling fertilization in cases with antispermatozoal antibodies (ASAB). PROST has provided useful diagnostic information in the management of couples who have failed to conceive in other treatment programs and has particular advantages over IVF for those receiving fresh donated oocytes for ovarian failure. Fourteen pregnancies resulted from 52 transfers, providing a pregnancy rate of 27% per transfer. The pregnancy rates were higher than a matched IVF series in the male factor and female ASAB groups and reached statistical significance for the ovum donation group. It is anticipated that both pregnancy rates and fetal wastage will be improved over conventional IVF and embryo transfer for the described infertility groups.


Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes.
Lung Krüppel-like factor (LKLF/KLF2) is an endothelial transcription factor that is crucially involved in murine vasculogenesis and is specifically regulated by flow in vitro. We now show a relation to local flow variations in the adult human vasculature: decreased LKLF expression was noted at the aorta bifurcations to the iliac and carotid arteries, coinciding with neointima formation. The direct involvement of shear stress in the in vivo expression of LKLF was determined independently by in situ hybridization and laser microbeam microdissection/reverse transcriptase-polymerase chain reaction in a murine carotid artery collar model, in which a 4- to 30-fold induction of LKLF occurred at the high-shear sites. Dissection of the biomechanics of LKLF regulation in vitro demonstrated that steady flow and pulsatile flow induced basal LKLF expression 15- and 36-fold at shear stresses greater than approximately 5 dyne/cm2, whereas cyclic stretch had no effect. Prolonged LKLF induction in the absence of flow changed the expression of angiotensin-converting enzyme, endothelin-1, adrenomedullin, and endothelial nitric oxide synthase to levels similar to those observed under prolonged flow. LKLF repression by siRNA suppressed the flow response of endothelin-1, adrenomedullin, and endothelial nitric oxide synthase (P < 0.05). Thus, we demonstrate that endothelial LKLF is regulated by flow in vivo and is a transcriptional regulator of several endothelial genes that control vascular tone in response to flow.


A perfect storm: An anomalous offshore phytoplankton bloom event in the NE Atlantic (March 2009).
While primary productivity is more stable in oceanic regions, it may vary to a great extent with the proximity to coasts, where mesoscale processes may intertwine and shape phytoplankton community composition and biomass. Sometimes, this may lead to the development of anomalous phytoplankton blooms (i.e., episodic blooms that exceed several times the average phytoplankton biomass). A massive bloom observed off the Western Iberian Coast (SW Europe) during March 2009 prompted a full investigation on its spatial and temporal extent, its causes, and its potential impact on the ecosystem. Results revealed that the March 2009 bloom was both novel in terms of biomass in a regional context and one of the largest anomalous blooms until now described in terms of relative magnitude. Its causes were due to a concurrence of long-term (deep winter MLD) and short-term factors (coastal upwelling, sudden changes in the water column, consistent offshore water transport). Its impact on the regional ecosystem is difficult to gauge, although the high concentrations of particulate organic carbon at surface during the bloom period suggests that it may have had a significant local impact. Since climate change is expected to increase the frequency and intensity of extreme weather events, it is possible that anomalous blooms will also become more frequent, expanding their role in shaping carbon export and food webs. These results are crucial for the monitoring of the Western Iberian Coast and are applicable to other complex coastal upwelling regions where phytoplankton biomass and variability have a crucial link to fisheries.


Rat testis during 2,5-hexanedione intoxication and recovery. I. Dose response and the reversibility of germ cell loss.
The histopathology of the testicular injury induced by 2,5-hexanedione (2,5-HD) exposure was examined in the rat. Charles River CD rats (200 g) were intoxicated by consuming 1% 2,5-HD in the drinking water or by intraperitoneal injection of the toxicant. Both neurotoxic and subneurotoxic exposures were studied, the total dose ranging from 40 to 211 mmol/kg. The following results were obtained: (1) there was a time delay between administration of the toxicant and development of the testicular injury, (2) Sertoli cell vacuolation in stages associated with the meiotic metaphase was the first histological sign of cellular injury at all doses, (3) subneurotoxic doses produced selective defects in germ cells in stages I-VIII of the spermatogenic cycle, (4) both subneurotoxic and neurotoxic doses produced germ cell necrosis and generalized sloughing of germ cells, and (5) intensive intoxication followed by a 17-week recovery period resulted in an absence of all postspermatogonial germ cells from the seminiferous epithelium of three of five treated rats. These data demonstrate that 2,5-hexanedione-induced testicular atrophy occurs at exposure levels below those producing clinical neurotoxicity and that, within the time frame of this study, the testicular injury is at least partially irreversible.


Perspective of educational environment on students' perception of teaching and learning.
Cross-sectional research was designed using the Dundee Ready Education Environment Measure (DREEM) to examine the impact of the educational environment on students' perceptions of learning and teaching in a university offering higher education. Using a Likert scale, 300 participants from various streams were assessed. There were no disparities in the students' judgments in the five DREEM categories of discipline, accommodation, gender, level of study, and disciplines. In general, students judged that the student-teaching environment was satisfactory. To investigate the validity of the DREEM, we conducted Cronbach alpha analysis and exploratory factor analysis (EFA) employing principal component analysis with varimax rotation. Only 44 of the 50 factors were deemed to be significant, with a cumulative explained variance of 46.539%. The total construct dependability of the EFA nine-factor solutions was 0.954. Finally, only five acceptable factors explained 46.539% variance using the criteria of eigenvalue > 1 and Cronbach's alpha > 0.6. Factor analysis was appropriate as evidenced by the Kaiser-Meyer-Olkin Measure of Sampling Adequacy of 0.942. With a Cronbach alpha of 0.955, the revised first domain of "student perception of learning" was the most trustworthy DREEM item, accounting for 20.19% of the variance. The highest factor loading was for the item "Teaching helps me become a more active learner". A redesigned DREEM might be valuable for assessing the educational environment at institutions providing higher education.


Lymphadenectomy via a cervical approach for upper mediastinal lymph node recurrence of esophageal cancer: report of a case.
Although there have been several reports about salvage esophagectomy after definitive chemoradiotherapy (CRT), the effectiveness of lymphadenectomy for lymph node recurrence after CRT has not been fully evaluated. Radiation-induced tissue injury and fibrosis make lymphadenectomy after CRT difficult, therefore the choice of surgical approach should be considered carefully. We performed lymphadenectomy via a cervical approach in a 76-year-old man with upper mediastinal lymph node recurrence. He had previously undergone subtotal esophagectomy for squamous cell carcinoma of the upper thoracic esophagus. At 33 months after the operation, left upper mediastinal lymph node recurrence occurred. After localized CRT with docetaxel plus 60 Gy radiation, the tumor disappeared. However, at 1 year after CRT a lymph node recurrence, measuring 10 mm in size, was found in the same position on a computed tomography (CT) scan and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) without other recurrences. Lymphadenectomy was performed via a left cervical approach using a Kent retractor to extend the surgical view of the cervicothoracic region. The patient was discharged without complications, and a postoperative CT scan and FDG-PET revealed complete resection of the tumor. In conclusion, our surgical procedure provides a good surgical view, and decreases surgical stress and the incidence of postoperative complications.


3-Phenyl-5-isothiazole carboxamides with potent mGluR1 antagonist activity.
The disclosed 3-phenyl-5-isothiazole carboxamides are potent allosteric antagonists of mGluR1 with generally good selectivity relative to the related group 1 receptor mGluR5. Pharmacokinetic properties of a member of this series (1R,2R)-N-(3-(4-methoxyphenyl)-4-methylisothiazol-5-yl)-2-methylcyclopropanecarboxamide (14) are good, showing acceptable plasma and brain exposure after oral dosing. Oral administration of isothiazole 14 gave robust activity in the formalin model of persistent pain which correlated with CNS receptor occupancy.


Characterization of Historical Methane Occurrence Frequencies from U.S. Underground Natural Gas Storage Facilities with Implications for Risk Management, Operations, and Regulatory Policy.
Defining a baseline for the frequency of occurrences at underground natural gas storage facilities is critical to maintaining safe operation and to the development of appropriate risk management plans and regulatory approaches. Currently used frequency-estimation methods are reviewed and broadened in this article to include critical factors of cause, severity, and uncertainty that contribute to risk. A Bayesian probabilistic analysis characterizes the aleatoric historical occurrence frequencies given imperfect sampling. Frequencies for the three main storage facility types in the United States (depleted oil-and-gas field storage, aquifer storage, solution-mined salt cavern storage) are generally on the order of 3 to 9 × 10-2 occurrences, of all causes (surface, well integrity, subsurface integrity) and severities (nuisance, serious, catastrophic), per facility-year. Loss of well integrity is associated with many, but not all, occurrences either within the subsurface or from there up to the surface. The probability of one serious or catastrophic leakage occurrence to the ground surface within the next 10 years, assuming constant number of facilities, is approximately 0.1-0.3% for any facility type. Storage operators and industry regulators can use occurrence frequencies, their associated probabilities and uncertainties, and forecasts of severity magnitudes to better prioritize resources, establish a baseline against which progress toward achieving a reduction target could be measured, and develop more effective mitigation/monitoring/reduction programs in a risk management plan.


Inflammatory Markers of CRP, IL6, TNFα, and Soluble TNFR2 and the Risk of Ovarian Cancer: A Meta-analysis of Prospective Studies.
There has been growing evidence showing that inflammatory markers play an important role in the development of ovarian cancer. We conducted a meta-analysis on the associations between circulating levels of C-reactive protein (CRP), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and soluble TNFα receptor 2 (TNFR2), and the risk of ovarian cancer. A systematic search of PubMed and EMBASE up until January 19, 2016 was conducted to retrieve prospective studies. The summary risk estimates were pooled using random-effects models. The dose-response relationship was assessed using generalized least-squares trend estimation. Seven nested case-control studies and one prospective cohort study were included in the review. For circulating CRP, women in the highest category had a significantly increased risk of ovarian cancer than women in the lowest category, with no significant between-study heterogeneity [pooled relative risk (RR) = 1.91; 95% confidence intervals (CI) 1.51-2.40; P < 0.001; I(2) = 0.0%]. Influence analyses further supported this positive association. A positive dose-response relationship was also observed (pooled RR = 1.15; 95% CI, 1.03-1.30 per 5 mg/L of CRP). Publication bias was found. However, the association persisted after correction using the trim-and-fill method. No significant association was observed for circulating IL6, TNFα, and soluble TNFR2. This meta-analysis provides evidence that elevated levels of CRP, but not circulating IL6, TNFα, or soluble TNFR2, are significantly associated with an increased risk of ovarian cancer. These results suggest that circulating CRP may play a role in the etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(8); 1231-9. ©2016 AACR.


Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides.
A model of acute carbon monoxide poisoning combined with spreading depression (SD) induced metabolic stress was used to examine the protective effects of cerebrolysin (CL) on the development of electrophysiological, behavioral and morphological signs of hypoxic damage. Capillary electrodes were implanted into the neocortex and hippocampus of anesthetized rats which were then exposed for 90 min to breathing of 0.8% to 0.5% CO, while 3 to 4 waves of cortical and hippocampal SD were elicited by microinjections of 5% KCl. Duration of SD-provoked depolarization of cerebral cortex and hippocampus was noted. Nine and 18 to 19 days later propagation of SD waves was recorded with the same electrodes and decrease of their amplitude was used as an index of brain damage which was significant in the hippocampus but not in the cortex. CL-treatment (2.5 ml/kg per day) started after CO administration and continued for 14 days significantly improved hippocampal recovery manifested by increased amplitude of SD waves. Behavioral tests performed 10 and 20 days after CO poisoning in the Morris water maze revealed better performance (escape latency 7 s) in the CL-treated than in untreated animals (14 s). Morphological analysis showed marked damage in the hippocampus consonant with electrophysiological and behavioral findings in the same animals. No apparent histological damage was found in rats exposed to CO inhalation alone without the additional SD-provoked depolarization. It is concluded that chronic CL-treatment enhances recovery of hippocampal tissue after hypoxic damage of intermediate severity.


Monoclonal anti-cardiolipin antibodies bind to DNA.
BALB/c mice immunized with the phospholipid, cardiolipin, produced anti-cardiolipin and anti-DNA antibodies. Seven hybridomas derived from spleen cells of the cardiolipin-immunized mice produced cardiolipin-binding monoclonal antibodies that also bound to the polynucleotides DNA, poly(dT), and poly(I). The seven cardiolipin-induced monoclonal antibodies shared idiotypic determinants with a high frequency idiotypic marker of spontaneously expressed anti-DNA autoantibodies of lupus-prone MRL-lpr/lpr mice. The monoclonal antibodies presumably bound to phosphodiester phosphate groups that occur in both polynucleotides and phospholipids. The results imply that production of anti-DNA autoantibodies does not require immunization by DNA.


Comparison of the analgesic effect of betamethasone and diclofenac potassium in the management of postoperative haemorrhoidectomy pain.
Outpatient postoperative haemorrhoidectomy pain remains a difficult problem. The purpose of this study is to compare the results of the use of betamethasone with diclofenac potassium in postoperative pain following haemorrhoidectomy. Closed haemorrhoidectomy was performed on 40 patients who were diagnosed grade III, grade IV haemorrhoid on physical examination. Patients were divided equally randomized into two groups, prospectively (betamethasone was used for 20 patients and diclofenac potassium was given for 20 patients). A verbal categorical scale was used to evaluate postoperative pain (for pain intensity, none=0, mild=1, moderate=2 and severe=3). The amount of narcotics required on postoperative first, second and third day were significantly less in the betamethasone group than in the diclofenac potassium group (P < 0.001) (Pearson Chi-Square test). Results indicate that use of betamethasone provides more effective analgesia than diclofenac potassium for postoperative pain management in the haemorrhoidectomy patient.


Is cognitive training an effective tool for improving cognitive function and real-life behaviour in healthy children and adolescents? A systematic review.
Computerised cognitive training (CCT) has been applied to improve cognitive function in pathological conditions and in healthy populations. Studies suggest that CCT produces near-transfer effects to cognitive functions, with less evidence for far-transfer. Newer applications of CTT in adults seem to produce certain far-transfer effects by influencing eating behaviour and weight loss. However, this is more unexplored in children and adolescents. We conducted a systematic review of 16 studies with randomised controlled design to assess the impact of CCT on cognitive functioning and real-life outcomes, including eating behaviour, in children and adolescents with typical development (PROSPERO registration number: CRD42019123889). Results show near-transfer effects to working memory, with inconsistent results regarding far-transfer effects to other cognitive functions and real-life measures. Long-term effects show the same trend. Far-transfer effects occurred after cue-related inhibitory control and attentional training, although effects seem not to last. CCT may be a potential weight-loss treatment option but more research is needed to determine the specific characteristics to enhance treatment outcomes.


Functioning adrenocortical oncocytoma: a case report and review of the literature.
Adrenocortical oncocytoma is exceptionally rare. Most of these tumors are benign and nonfunctioning. We report a case of functioning adrenocortical oncocytoma located in the right adrenal gland in a 53-year-old woman who presented with Cushing's syndrome. The tumor was small, with exclusively oncocytic histologic features. A discussion of this case and a review of the literature on this entity is presented.


Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex.
mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis. In TSC2-deficient cells and tumors, we find that mTORC1 inhibitors shift cellular dependence from MCL-1 to BCL-2 and BCL-XL for survival, thereby altering susceptibility to BH3 mimetics that target specific pro-survival BCL-2 proteins. The BCL-2/BCL-XL inhibitor ABT-263 synergizes with rapamycin to induce apoptosis in TSC-deficient cells and in a mouse tumor model of TSC, resulting in a more complete and durable response. These data expose a therapeutic vulnerability in regulation of the apoptotic machinery downstream of mTORC1 that promotes a cytotoxic response to rapamycin.


Genetic ablation of Fas-activated serine/threonine kinase ameliorates obesity-related hepatic glucose and lipid metabolic disorders via sirtuin-1 signaling.
Obesity has become a worldwide pandemic and is associated with various metabolic diseases such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. Fas-activated serine/threonine kinase (Fastk) is a multifunctional protein localized in the mitochondrion; however, the role of Fastk in obesity-related metabolic disorders remains unexplored. Here we found that Fastk expression was specifically induced in livers of high fat (HF) diet-fed mice and in saturated fatty acid (such as palmitate)-loaded hepatocytes. Genetic ablation of Fastk ameliorated HF diet-induced insulin resistance, glucose intolerance, and hepatic steatosis. Further studies confirmed that Fastk knockout suppressed hepatic gluconeogenesis and lipogenesis in HF diet-stressed livers and in palmitate-loaded hepatocytes. Mechanistically, Fastk ablation significantly preserved sirtuin-1 (SIRT1) expression and activity in livers of HF diet-fed mice and in palmitate-loaded hepatocytes. Inhibition of SIRT1 activity by EX-527 (a specific inhibitor of SIRT1) totally abolished the suppressive effects of Fastk knockout on gluconeogenesis and lipogenesis in cultured hepatocytes. In conclusion, these data for the first time demonstrate that Fastk critically controls hepatic gluconeogenesis and lipogenesis mainly through modulating SIRT1 signaling. Intervening Fastk expression or activity might be a promising therapeutic strategy for the treatment of obesity-associated metabolic diseases.


Predictors of infection-related rehospitalization in heart failure patients and its impact on long-term survival.
Infection is the most common non-cardiovascular cause of re-hospitalizations for heart failure patients. We therefore investigated the predictors of infection-related re-hospitalization (IRRH) in heart failure patients and its impact on long-term survival. We prospectively recruited 622 patients after the index hospitalization for decompensated heart fail with primary endpoints of IRRH and all-cause mortality. During follow-up of 3.9 ± 2.7 years, IRRHs occurred in 104 (16.7%) patients. Of the 104 patients who experienced IRRHs, the time from the index hospitalization to IRRH was 1.0 (interquartile range: 0.4-2.6) years. Independent predictors of IRRH were age (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04), diabetes mellitus (2.12, 1.42-3.17), not taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (1.67, 1.01-2.78), needing maintenance therapy with a loop diuretic (2.10, 1.36-3.26), hemoglobin levels (0.87, 0.79-0.96), and estimated glomerular filtration rates (eGFRs) (0.99, 0.98-0.99). IRRH independently predicted all-cause mortality (1.99, 1.32-2.98) after adjusting for age, body mass index, New York Heart Association functional class, chronic obstructive pulmonary disease, brain natriuretic peptide, hemoglobin, and eGFR. The increased risk of death associated with IRRHs was predominantly for lower respiratory tract infections (3.71, 2.28-6.04), urogenital tract infections (2.83, 1.32-6.10), and sepsis (3.26, 1.20-8.85). IRRHs in patients discharged for acute decompensated heart fail independently predicted worse long-term survival. We further identified independent predictors of IRRHs. These findings warrant future studies for tackling IRRH.


Prednisone and low-dose activated prothrombin complex concentrates for FVIII inhibitor in nonhaemophilic patients.
Eight nonhaemophilic patients with factor VIII (FVIII) inhibitors were reported. There was no difference in sex distribution. Median age at diagnosis was 62 years (ranging from 14 to 73 years). No associated disorders were revealed and all the patients were presented with severe muscular or arthral bleeding. Inhibitor titre was measured by the Bethesda method, which were 6.4, 126.0, 155.0, 4.8, 56.0, 13.5, 35.0 and 150.0 BU mL-1, respectively, at diagnosis. FVIII:C levels were less than 1 U dL-1 in seven patients and less than 2 U dL-1 in one patient. The median vWF:Ag level was 210% (ranging from 80% to 340%). All the patients had good response to activated prothrombin complex concentrates for acute bleeding episodes and prednisone for inhibitor elimination. Inhibitors completely eliminated in seven patients within a follow-up duration over 1 year, and one patient died of intracranial haemorrhage when her inhibitor titre decreased to 4.5 BU mL-1 and FVIII:C increased to 21 U dL-1.


Superficial radial sensory neuropathy: Medial and lateral branch injury.
Superficial radial sensory nerve (SRN) injury may involve the main nerve or its distal medial or lateral branch. We investigated the utility of SRN conduction studies on the medial and lateral branches in patients with suspected SRN injury. Fifteen patients with symptoms of SRN neuropathy were studied. Their clinical and electrophysiological findings were assessed according to sensory symptom areas. Three active recording electrode positions were used: snuff box (position A); medial branch (position B); and lateral branch (position C). In 7 patients with medial area symptoms, abnormal findings were seen in position B (100%) and position A (71%). In 3 patients with medial and lateral area symptoms, abnormal findings were seen in all positions. In 5 patients with lateral symptoms, abnormal findings were seen in position C only. Nerve conduction studies for each branch of the SRN are useful in patients with suspected SRN neuropathy.


Relation of alpha 2-macroglobulin and other antiproteases to the clinical features of acute pancreatitis.
alpha 2-macroglobulin is probably the most important of the antiproteases in plasma. In this study, the relationships of plasma alpha 2-macroglobulin to the clinical features of acute pancreatitis as well as to plasma levels of other antiproteases, immunoglobulins, and immunoreactive trypsin, were investigated in 55 patients with acute pancreatitis. The mean level of alpha 2-macroglobulin in 395 plasma samples from the patients was 2.12 g/liter compared with 2.41 g/liter in 29 healthy subjects and 2.93 g/liter in 17 patients with septicemia. Plasma levels were lower in 12 patients with severe pancreatitis than in 43 with mild attacks, and the lowest levels in three fatal attacks were less than half the mean of the normal range. Lowest levels were recorded at a mean time of 3 days after admission in the patients with mild attacks, at 5 days after admission in the patients with severe attacks, and 9 days after admission in those with fatal attacks. In contrast, plasma levels of the alpha 1-proteinase inhibitor antichymotrypsin and C-reactive protein increased to above normal levels during the attack, significantly more so in severe compared with mild attacks. Plasma levels of IgA, IgG, and IgM remained within the normal range or were increased. In patients with severe pancreatitis, plasma levels of immunoreactive trypsin remained elevated for longer than in those with mild attacks although there was little initial difference in the levels. These data suggest that decreasing levels of alpha 2-macroglobulin during the course of acute pancreatitis are due to a specific mechanism and unrelated, for the most part, to any generalized effect of pancreatitis on protein synthesis. The formation of rapidly cleared complexes between alpha 2-macroglobulin and active proteases is the most tenable explanation for the depletion of plasma levels, but the clinical significance of the changes remains unclear.


Determinants of species richness in southern African fig wasp assemblages.
We investigated the species richness of 24 fig wasp (Hymenoptera) assemblages associated with southern African fig trees (Ficus species, Moraceae). Assemblage sizes ranged between 3 and 30 species on different host tree species, with parasitoids slightly outnumbering gall-forming phytophages. Ten potential taxonomic, geographic and ecological determinants of assemblage richness were examined. Galler richness differed significantly between taxonomic sub-groups of Ficus and was significantly correlated with several ecological characteristics of the host trees, but there was no species-area effect. Parasitoid richness was strongly correlated with galler richness. We conclude that both ecological and historical factors have combined to determine the numbers of species that form fig wasp assemblages.


Influence of experience on kinematics of upper limbs during sewing gesture.
To teach a skilled motor task, it is crucial to understand the characteristics of expertise. The aim of the present study was to compare the kinematics of the hand sewing task between novices (n = 10), intermediates (n = 10) and experts (n = 10). Compared to novices and intermediates, the proximal joint of expert participants was less involved in the task than their distal joints. The shoulder of experts stayed closer to the trunk, while the ranges of motion of the wrist and fingers were higher. This ability enabled them to avoid lifting the arm, which was resting on the table. We observed a low cycle-to-cycle variability of the movement pattern for experts, while it was more variable in novices. Moreover, experts shared similar joints synergies attesting of an "experts" common gesture. This knowledge gained about the hand sewing kinematics can be used to refine the training process of dressmakers.


Transesophageal echocardiography and right atrial infarction.
Transesophageal echocardiographic findings in right atrial infarction are described. In three patients with myocardial infarction of one or both ventricles, the association of right atrial myocardial infarction was suspected because of anatomic (two-dimensional) and hemodynamic (Doppler) alterations obtained from transesophageal images. Transesophageal interrogation may prove widely applicable in the evaluation of patients with suspected right atrial infarction.


Morphometric study of the sensory nerve in classical (or Charcot disease) and juvenile amyotrophic lateral sclerosis.
Analysis of the superficial peroneal nerve sampled in 9 cases of classical amyotrophic lateral sclerosis (classical ALS, Charcot disease) and compared with 8 age-matched controls showed a very significant reduction of all myelinated fibres (P less than 0.001), affecting small-diameter (P less than 0.01) and large-diameter (P less than 0.02) fibres. Moreover, the small-diameter unmyelinated fibres were very significantly reduced (P less than 0.001) and the large-diameter fibres were highly increased (P less than 0.01). These results suggest a phenomenon of chronic axonal degeneration. Analysis of the same nerve in 7 patients suffering from juvenile ALS and compared with 4 age-matched controls showed a significant reduction (P less than 0.05) of myelinated fibres. The small-diameter and overall unmyelinated fibres were not significantly reduced while the large-diameter fibres, were significantly increased (P less than 0.01). The same analysis of 4 patients presenting an early-onset ALS compared with 3 controls showed lesions of a severity half-way between that of the classical and the juvenile form. Our study showed that the lesions of the sensory nerve are of the same type in classical ALS and in juvenile ALS, but of differing severity. The nosologic place of juvenile ALS compared with classical ALS and with heredodegenerative diseases of the nervous system is discussed.


Elucidating the role of microstructural modification on stress corrosion cracking of biodegradable Mg4Zn alloy in simulated body fluid.
This paper investigates the effect of microstructure modification by heat treatment on stress corrosion cracking (SCC) behavior of Mg4Zn alloy in simulated body fluid (SBF). Mg4Zn alloy in as cast, solution heat treated and peak aged conditions was susceptible to SCC in SBF when strained at 3.6 × 10-6 s-1. SCC index based on fracture energy is least for solutionized alloy (0.84), while 0.88 for as cast and peak aged alloys. Fractographic analysis indicates predominantly intergranular SCC for solution treated alloy initiated by anodic dissolution near grain boundaries. As cast and peak aged alloy shows mainly transgranular failure due to hydrogen embrittlement adjacent to secondary phase particles.


The imidacloprid remediation, soil fertility enhancement and microbial community change in soil by Rhodopseudomonas capsulata using effluent as carbon source.
The effects of Rhodopseudomonas capsulata (R. capsulata) in the treated effluent of soybean processing wastewater (SPW) on the remediation of imidacloprid in soil, soil fertility, and the microbial community structure in soil were studied. Compared with the control group, with the addition of effluent containing R. capsulata, imidacloprid was effectively removed, soil fertility was enhanced, and the microbial community structure was improved. Molecular analysis indicated that imidacloprid could exert induction effects on expression of cpm gene and regulation effects on the synthesis of cytochrome P450 monooxygenases (P450) by activating HKs gene in two-component system (TCS). For R. capsulata, this induction process required 1 day. The synthesis of P450 occurred 1 day after inoculation, because R. capsulata are a type of archaea and imidacloprid is an environmental stress. Before expression of the cpm gene and synthesis of P450, R. capsulata need a period of time to adapt to external imidacloprid stimulation. However, the lack of organic matter in the soil cannot sustain R. capsulata growth for more than 1 day. In four groups with added effluent, the remaining organic matter in the effluent provided a sufficient carbon source and energy for R. capsulata. Five days later, the microbial community structure was improved by R. capsulata in the soil. The new technique could be used to remediate imidacloprid, enhance soil fertility, treat SPW and realize the recycling and reuse of wastewater and R. capsulata cells.


Ptychoptera deleta Novák, 1877 from the Early Miocene of the Czech Republic: redescription of the first fossil attributed to Ptychopteridae (Diptera).
The first fossil that was described in Ptychopteridae, Ptychoptera deletaNovák, 1877 from the classical Early Miocene locality Mokřina (Krottensee) in western Bohemia is re-examined. The re-description of the holotype including a new line drawing and remarks summarizing the scarce fossil record of this group is provided.


Mechanisms to prevent the toxicity of chronic neuroinflammation on forebrain cholinergic neurons.
Inflammatory processes may play an important role in the degeneration of basal forebrain cholinergic cells Alzheimer's disease. We infused the proinflammagen lipopolysaccharide into the basal forebrain of young rats and determined whether the chronic administration of two novel non-steroidal anti-inflammatory drugs or a pan-caspase synthesis inhibitor, z-Val-Ala-Asp(OMe)-fluoromethyl ketone (zVAD), could provide neuroprotection from the cytotoxic effects of the neuroinflammation. Chronic lipopolysaccharide infusions decreased choline acetyltransferase activity and increased the number of activated microglia within the basal forebrain region. The level of caspases 3, 8 and 9 was increased in ventral caudate/putamen. Non-steroidal anti-inflammatory drug therapy attenuated the toxicity of the inflammation upon cholinergic cells and reduced caspases 3, 8 and 9 activity in the caudate/putamen. zVAD treatment significantly decreased the levels of caspases 3, 8 and 9 but did not provide neuroprotection for the cholinergic neurons. These results suggest that prostaglandins contribute to the degeneration of forebrain cholinergic neurons in Alzheimer's disease.


A qPCR assay for measuring the post-integrational DNA repair in HIV-1 replication.
The post-integrational gap repair is a critical and poorly studied stage of the lentiviral life cycle. It might be performed by various cellular DNA repair pathways but the exact mechanism of the repair process has not yet been described. One of the reasons for that is the lack of a functional quantitative assay that could precisely measure the amount of integrated viral DNA that has completed the post-integrational gap repair stage. Here, we present an approach that is based on a widely used Alu-specific PCR for the estimation of integrated viral DNA but includes several steps that allow discrimination between integrated-repaired and integrated-unrepaired viral DNA forms. We used the approach for the estimation of the kinetics of gap repair in a viral vector system and showed that the gap repair process starts at 17 h post infection and lasts 10 more hours. We also showed that the addition of Nu7441 - a small molecule inhibitor of DNA-breaks sensor kinase in the non-homologous end joining DNA repair pathway - specifically inhibits the gap repair process while having no influence on the integration itself.


The sellar barrier on preoperative imaging predicts intraoperative cerebrospinal fluid leak: a prospective multicenter cohort study.
The type of sellar barrier observed between a pituitary tumor and cerebrospinal fluid (CSF) on preoperative magnetic resonance imaging (MRI) may predict intraoperative CSF leak during endonasal pituitary surgery. This is the first multicentric prospective cohort trial to study the sellar barrier concept and CSF leak rate during endoscopic pituitary surgery. This multi-center, international study enrolled patients operated for pituitary adenomas via fully endoscopic endonasal surgery over a period of 4 months. The independent variable was the subtype of sellar barrier observed on preoperative MRI (strong, mixed or weak); the dependent variable was the presence of an intraoperative CSF leak. The primary goal was to determine the association between a particular type of sellar barrier and the risk of intraoperative CSF leak. Appropriate statistical methods were then applied for data analysis. Over the study period, 310 patients underwent endoscopic endonasal surgery for pituitary tumor. Preoperative imaging revealed a weak sellar barrier in 73 (23.55%), a mixed sellar barrier in 75 (24.19%), and a strong sellar barrier in 162 (52.26%) patients. The overall rate of intraoperative CSF leak among all patients was 69 (22.26%). A strong sellar-type barrier was associated with significantly reduced rate of intraoperative CSF leak (RR = 0.08; 95% CI 0.03-0.19; p < 0.0001), while a weak sellar barrier associated with higher rates of CSF leak (RR = 8.54; 95% CI 5.4-13.5; p < 0.0001). The preoperative MRI of pituitary patients can suggest intraoperative CSF leak rates, utilizing the concept of the sellar barrier. Patients with a weak sellar barrier carry a higher risk for an intraoperative CSF leak, whereas a strong sellar barrier on MRI seems to mitigate intraoperative CSF leak. We propose that preoperatively assessment of the sellar barrier can prepare surgeons for intraoperative CSF leak repair.


Metabolism of bromobenzene. Analytical chemical and structural problems associated with studies of the metabolism of a model aromatic compound.
Our studies of bromobenzene metabolism have shown that the 3,4-oxide is metabolized to 3- and 4-bromophenol through an extended glutathione pathway. The mechanism of sulfur elimination from a dihydrobromobenzene metabolite is not known, although it is known that the aromatization reaction will occur in a 9000-g supernatant fraction of rat liver. The hepatotoxic and nephrotoxic metabolites of bromobenzene are most likely bromthiocatechols and a bromothiopyrogallol, respectively.


Survival and reproduction in some algae under stress conditions.
Pithophora oedogonia and Cladophora glomerata survived lowest 60 and 58%, respectively, in June when the pond diurnal water temperature (PDWT) increased to a maximum of 28 degrees C. The lowering of PDWT only by 1 degrees C in July improved survivability of both algae to their almost maximum level of 100 and 96%, respectively. Further lowering of PDWT to 17-22 degrees C in November initiated akinete formation in P. oedogonia. The process of akinete initiation, maturation and germination continued till April when PDWT increased to 20-24 degrees C, but not beyond that in May when PDWT was 21-26 degrees C. By this time, probably all akinetes have germinated in situ, and the alga was entirely vegetative. P. oedogonia population is not synchronous in nature, since during the 5-6-month reproductive season, some filaments were in active vegetative stage, some had akinete initiation, some had completed akinete formation, and some had akinetes germinating. C. glomerata grew dense vegetative in November and initiated (zoo)sporangial primordia formation (to some extent) in February (when PDWT was lowest, viz. 10-14 degrees C) till April. Meanwhile, no (zoo)-sporangial primordia either produced any zoospore or germinated into a germ tube; and all released their cytoplasmic content and died (along with some vegetative cells) with an increase in PDWT to 21-26 degrees C in May. Vaucheria geminata vegetative patches appeared on the soil surface, 2nd week of January by lowering of atmospheric diurnal temperature (ADT) to 9-16 degrees C in the 1st week. The alga started sexual reproduction by the 2nd week of March (when ADT increased to 20-23 degrees C) and completed the process of reproduction by the 1st week of April (when ADT increased to 24-26 degrees C) and died thereafter. P. oedogonia, C. glomerata and V. geminata survived better and longer in submerged conditions than air-exposed (which was true for P. oedogonia and C. glomerata aquatic habitat and also indicated that the soil alga V. geminata could survive to some extent if submerged in rain water). P. oedogonia formed akinetes and C. glomerata (zoo)sporangial primordia only in submerged condition and not when air-exposed on moist soil surface. V. geminata did not complete the life cycle both under submerged and air-exposed conditions. Vegetative survival in P. oedogonia, C. glomerata, V. geminata, Aphanothece pallida, Gloeocapsa atrata, Scytonema millei, Myxosarcina burmensis, Phormidium bohneri, Oscillatoria animalis, O. subbrevis, Lyngbya birgei, L. major, Microcoleus chthonoplastes and Rhizoclonium crassipellitum, reproduction in P. oedogonia, C. glomerata and V. geminata, cell division in A. pallida and G. atrata, heterocyst and false branch formation in S. millei, all, were adversely affected at approximately 28.5 degrees C for t12 h at light intensity of approximately 160 micromol m(-2) s(-1); high intensity does not ameliorate high temperature damage to any algae. The presence of liquid water, than its absence, outside the different algae moderated the severity of heat to some extent but not when the heat was severe.


Quantitative analysis of adipose tissue for predicting Crohn's disease postoperative endoscopic recurrence and anastomotic ulcer.
Inflammation and ulcers at the anastomotic site are frequently observed after intestinal resection surgery for Crohn's disease (CD), which often signify postoperative recurrence. Crohn's disease causes abnormalities in whole-body fat metabolism, and alterations in subcutaneous and visceral fat are potential indicators of disease development. This study aimed to quantify the areas of subcutaneous (SFA) and visceral fat (VFA) and investigate the relationship between fat tissue and endoscopic recurrence and anastomotic ulceration after Crohn's disease surgery. We conducted a retrospective analysis of clinical data from 279 patients diagnosed with Crohn's disease. Using abdominal CT (Computed Tomography) scans at the level of the umbilicus, we measured the area of subcutaneous and visceral fat, and calculated the Mesenteric Fat Index (MFI), which is defined as the ratio of the area of visceral fat to subcutaneous fat. We compared the changes in fat tissue between surgical Crohn's disease patients and non-surgical patients in remission, as well as changes in fat tissue before and after surgery, and between patients with and without endoscopic recurrence after surgery. The MFI value of the surgical group was higher than that of the non-surgical group(0.88(1.27 ± 1.26) VS 0.39(0.44 ± 0.21), P < 0.001), while the SFA value was lower(70.16(92.97 ± 78.23) VS 157.64(175.96 ± 101.58), P < 0.001). Of the 134 surgical patients who underwent abdominal CT examination after surgery, the SFA value was significantly higher after surgery(143.61 ± 81.86 VS 90.87 ± 71.93, P < 0.001), and the MFI value decreased accordingly(0.57 ± 0.36 VS 1.30 ± 1.35, P < 0.001). Multivariate Cox analysis indicated that high VFA and MFI values, smoking history, and preoperative biologic therapy were all risk factors for postoperative endoscopic recurrence(p < 0.05), while high MFI values and preoperative biologic therapy were also risk factors for anastomotic ulcers(p < 0.05). The Kaplan-Meier analysis showed that these factors increased the risk of reaching the endpoint with time(p < 0.05). The ROC curve results showed that MFI value had high diagnostic value for postoperative endoscopic recurrence [AUC:0.831, 95% CI: 0.75-0.91, p < 0.001] and anastomotic ulcers [AUC:0.801, 95% CI: 0.71-0.89, p < 0.001]. Surgical CD patients have significantly higher MFI values but the values decline after surgery. When the preoperative MFI value is > 0.82, the risk of postoperative endoscopic recurrence increases significantly, and when the MFI value is ≥ 1.10, the risk of anastomotic ulceration after surgery increases significantly. Meanwhile, biologic therapy preoperatively also is a high-risk factor for early postoperative endoscopic recurrence or anastomotic ulcers after intestinal resection surgery.


Reconstituted spray-dried phenytoin-loaded nanocapsules improve the in vivo phenytoin anticonvulsant effect and the survival time in mice.
This study evaluated the in vivo anticonvulsant effect of a spray-dried powder for reconstitution containing phenytoin-loaded lipid-core nanocapsules. The effect of chitosan coating on redispersibility, gastrointestinal stability, and drug release from nanoparticles was evaluated during the development of the powders. Maltodextrin was used as adjuvant in the spray-drying process. Chitosan coating played an important role in redispersibility, and large particles (>100 μm) were obtained using the highest concentration of solids in the feed. However, after aqueous redispersion, volume-based particle size was reduced to about 1 µm. The release of nanoparticles from the surface of the spherical microagglomerates (roundness index = 0.75) was confirmed by SEM analysis. Powders reconstituted in water recovered partially the nanometric properties of the original suspensions and were stable for 24 h. Phenytoin-loaded chitosan-coated nanocapsules and their redispersed powders have good gastrointestinal stability, and are able to control drug release in simulated gastric and intestinal fluids. Besides that, the reconstituted powder containing chitosan-coated nanocapsules exhibited improved anticonvulsant activity against seizures induced by pilocarpine in mice, compared to the non-encapsulated drug, representing an important approach in anticonvulsant treatments for children and adults.


Three-dimensional computer reconstruction of prostate cancer from radical prostatectomy specimens: evaluation of the model by core biopsy simulation.
A technique was developed for three-dimensional (3D) modeling of prostate cancer and transrectal biopsies. To test the model, the cancer yield of a simulated 10-biopsy protocol was compared with a simulated sextant protocol and with preoperative biopsies regarding cancer detection and correlation with tumor volume. Transrectal ultrasound-guided core biopsies were taken from 81 men according to a standardized 10-biopsy protocol that included sextant biopsies. The patients underwent radical prostatectomy and specimens were step-sectioned and whole-mounted. Cancer and the prostate capsule were outlined on the slides and the regions transferred to a computer software program developed by our group. A 3D volume of each prostate was reconstructed from the sections. Virtual core biopsy needles imitating the positions of the real biopsies were inserted into the prostate and the cancer yield was calculated. Only the standardized positions were considered in this study (ie, additional biopsies from hypoechoic foci were not accounted for). Of the cancers detected with 10 standardized virtual biopsies, 24% would have remained undetected with sextant biopsies. The cancer yield of 10 virtual biopsies correlated with the preoperative biopsies (r = 0.64) and with the tumor volume (r = 0.56). A multiple regression analysis showed that the cancer yield of a simulation of 10 biopsies correlated better with tumor volume than did a simulation of sextant biopsies (P = 0.02). We conclude that computer-assisted 3D reconstruction of prostate cancer can be used as a model for evaluation and optimization of biopsy protocols.


Acetylcholinesterase activity in rectal mucosa and blood in the diagnosis of Hirschsprung's disease.
Histochemical and biochemical examinations of rectal biopsy specimens were performed in 13 patients with Hirschsprung's disease and in seven with idiopathic constipation and no megacolon. Serum and erythrocyte acetylcholinesterase (AchE) activity in these two groups was compared with that in 30 normal controls. AchE staining of rectal biopsy specimens proved to be a reliable and convenient diagnostic approach in patients with Hirschsprung's disease. Biochemical assay of AchE activity in rectal biopsy specimens was also of value in the diagnosis, however, there was an overlap between Hirschsprung's disease and idiopathic constipation. Erythrocyte AchE activity correlated well with AchE activity in rectal biopsy specimens. Therefore, assays of erythrocyte AchE activity provided useful additional information, especially in screening tests for Hirschsprung's disease.


Assessment of an enhanced chemiluminescent immunometric assay for TSH in 1127 patients.
An enhanced immunochemiluminometric assay for serum TSH ('Amerlite', Amersham, Bucks, UK) was studied in 1127 patients in routine clinical practice to assess its value as a first-line test of thyroid status. Good correlation with clinical thyroid status was found in the untreated euthyroid patients, in the untreated hyperthyroid and hypothyroid patients, in pregnancy and in the sick euthyroid. However, a large proportion of clinically euthyroid patients with nodular goitre, as well as those treated by thyroidectomy, radioiodine or antithyroid drugs and those on replacement l-thyroxine showed TSH values outside the reference range. Therefore, additional tests are likely to be needed frequently in these categories.


Computer program for statistical Mann-Whitney U nonparametric analysis of neuronal spike activity.
A program for neuronal activity analysis is described. The applied computational techniques are standard in the field of digital processing, but the program is particular in its field of application and mode of data selection. The program, written in Turbo Pascal for the IBM-PC and compatibles, statistically compares (Mann-Whitney U-test) two sets of graphically selected data, and establishes whether there are significant differences between them. Although the program was developed for spike frequency analysis, it can easily be adapted to perform statistical analysis of other kinds of data.