Association of Gap-43 (neuromodulin) with microtubule-associated protein MAP-2 in neuronal cells.
Gap-43 (B-50, neuromodulin) is a presynaptic protein implicated in axonal growth, neuronal differentiation, plasticity, and regeneration. Its activities are regulated by its dynamic interactions with various neuronal proteins, including actin and brain spectrin. Recently we have shown that Gap-43 co-localizes with an axonal protein DPYSL-3 in primary cortical neurons. In the present study we provide evidence that Gap-43 co-localizes and potentially interacts with microtubule-associated protein MAP-2 in adult and fetal rat brain, as well as in primary neuronal cultures. Our studies suggest that this interaction may be developmentally regulated.


Cerebral and Extracerebral Vasoreactivity in Patients With Different Clinical Manifestations of Cerebral Small-Vessel Disease: Data From the Significance of Hemodynamic and Hemostatic Factors in the Course of Different Manifestations of Cerebral Small-Vessel Disease Study.
Endothelial dysfunction has been implicated in the pathogenesis of cerebral small-vessel disease (SVD). Little is known about the relationship between SVD and measures of endothelium-dependent vasodilatation and cerebral vasomotor reactivity. The aim of this study was to evaluate cerebral and extracerebral endothelial dysfunction in patients with different manifestations of SVD and to assess the relationship between endothelial dysfunction and radiologic markers of SVD. The vasomotor reactivity reserve (VMRr), breath-holding index (BHI) of the middle cerebral arteries, and brachial artery flow-mediated dilatation (FMD) were measured with ultrasound techniques in 90 patients (30 in each group) older than 60 years with extensive white matter lesions (Fazekas grade ≥ 2) with a history of lacunar stroke, vascular dementia, or parkinsonism and 30 individuals with normal magnetic resonance imaging findings (control group). All groups were matched for age, sex, hypertension, and diabetes. The mean age ± SD (71.8 ± 3.4 versus 71.7 ± 3.4 years), sex distribution, and prevalence of the main vascular risk factors were similar in the SVD and control groups. The VMRr (56.6% ± 18.3% versus 77.1% ± 16.9%), BHI (0.8 ± 0.3 versus 1.1 ± 0.4), and FMD (5.8% ± 4 versus 12.1% ± 5.2%) were severely impaired in the SVD groups compared to the control group (P < .01). The vascular responses to all tests was similar in the SVD groups, but they were significantly decreased in patients with severe white matter lesions, marked brain atrophy, and enlarged perivascular spaces. This study was the first that simultaneously evaluated cerebral and extracerebral vasodilator responses in a well-phenotyped cohort of patients with lacunar stroke, vascular dementia, or parkinsonism. The VMRr, BHI, and FMD were more severely impaired in patients with SVD, regardless of its clinical manifestation, than in control participants. All measures were significantly lower in patients with severe white-matter lesions, brain atrophy, or enlarged perivascular spaces.


Complications of Transoral Robotic Surgery.
This article summarizes major and minor complications following transoral robotic surgery in the head and neck. Overall, transoral robotic surgery is extremely safe; however, surgeons must recognize inherent risks associated with major and severe bleeding, dysphagia, and minor complications, including injury to nerves, mucosal surfaces, teeth, and the eyes. This article briefly discusses prevention and management strategies for common complications.


Interactions between cannabinoid and opioid receptors in a mouse model of diabetic neuropathy.
Diabetic neuropathy, often associated with diabetes mellitus, is a painful condition with no known effective treatment except glycemic control. Studies with neuropathic pain models report alterations in cannabinoid and opioid receptor expression levels; receptors whose activation induces analgesia. We examined whether interactions between CB1R and opioid receptors could be targeted for the treatment of diabetic neuropathy. For this, we generated antibodies that selectively recognize native CB1R-MOR and CB1R-DOR heteromers using a subtractive immunization strategy. We assessed the levels of CB1R, MOR, DOR, and interacting complexes using a model of streptozotocin-induced diabetic neuropathy and detected increased levels of CB1R, MOR, DOR, and CB1R-MOR complexes compared with those in controls. An examination of G-protein signaling revealed that activity induced by the MOR, but not the DOR agonist, was potentiated by low nanomolar doses of CB1R ligands, including antagonists, suggesting an allosteric modulation of MOR signaling by CB1R ligands within CB1R-MOR complexes. Because the peptide endocannabinoid, hemopressin, caused a significant potentiation of MOR activity, we examined its effect on mechanical allodynia and found that it blocked allodynia in wild-type mice and mice with diabetic neuropathy lacking DOR (but have CB1R-MOR complexes). However, hemopressin does not alter the levels of CB1R-MOR complexes in diabetic mice lacking DOR but increases the levels of CB1R-DOR complexes in diabetic mice lacking MOR. Together, these results suggest the involvement of CB1R-MOR and CB1R-DOR complexes in diabetic neuropathy and that hemopressin could be developed as a potential therapeutic for the treatment of this painful condition.


Alcohol consumption is associated with DXA measurement of adiposity: the Pró-Saúde Study, Brazil.
Evaluate the association between alcohol consumption and body adiposity. We analyzed cross-sectional data from a longitudinal investigation (Pró-Saúde Study), comprising a sample of 514 civil servants of both sexes (35-64 years). Daily alcohol consumption (wine, beer, and other alcoholic drinks) over the previous 6 months was assessed via food frequency questionnaire and categorized as no doses, up to 1 dose, and ≥1 dose. The total body mass, total fat mass (TFM), android fat mass (AFM), and gynoid fat mass (GFM) were measured via dual-energy X-ray absorptiometry. AFM (AFM%) and GFM (GFM%) were expressed as percentages relative to TFM. The ratio of AFM% and GFM% was calculated. Multiple linear regression analyses were performed after adjusting for age, calories not originating from alcohol, leisure-time physical activity and education. Among nondrinkers, 59 % were women, and the age range between 45 and 54 years was predominant (44.3 %); 63.7 % of the nondrinkers were overweight/obese. Among drinkers of 1 dose or more/day, 67 % were males aged between 45 and 54 years (43.7 %); 69.1 % were overweight/obese. Among men, the daily consumption of ≥1 alcohol dose (13 g) was associated with an approximately 2 % (β = 2.2, IC = 0.077; 4.303) adjusted for age, calories not originated from alcohol, leisure-time physical activity and education, increase in TFM, compared to those who reported no alcohol consumption during the previous 6 months. This association was not observed among women. In both sexes, no associations were observed between alcohol consumption and the other evaluated parameters of adiposity. Among men only, daily consumption of ≥1 alcohol dose was associated with increased adiposity, despite the relatively low average alcohol consumption in this study population.


Detection of anti-DNA antibodies: a comparison between two Farr assays, Crithidia luciliae and a human chromosomal substrate assay.
Four commercially available assays were compared with a 14C DNA Farr assay for their ability to detect anti-DNA antibodies in 119 sera from 109 patients with systemic lupus erythematosus (SLE) and 25 control sera. The 14C DNA Farr assay was the most sensitive and specific assay (SLE, 57% positive, controls, 0%). A commercial 125I DNA Farr assay was significantly less sensitive (SLE, 39% positive). The fluorescence human chromosomal preparation assay was as sensitive as the 14C DNA Farr assay (SLE, 58% positive) but less specific (controls, 8% positive). The immunofluorescence Crithidia luciliae assay was specific, but less sensitive (SLE, 37% positive) than the 14C DNA Farr assay. Adaptation of Crithidia to immunoperoxidase did not alter its sensitivity or performance. These results confirm that the 14C DNA Farr assay, locally refined and performed by experienced hands, is the most sensitive and specific assay for anti-DNA antibodies. The 125I DNA Farr was no more sensitive than the Crithidia assay but considerably more laborious. The human chromosomal preparation may be suitable as a rapid screening test for anti-DNA antibodies.


Electric field control of magnetic states in isolated and dipole-coupled FeGa nanomagnets delineated on a PMN-PT substrate.
We report observation of a 'non-volatile' converse magneto-electric effect in elliptical FeGa nanomagnets delineated on a piezoelectric PMN-PT substrate. The nanomagnets are first magnetized with a magnetic field directed along their nominal major axes. Subsequent application of a strong electric field across the piezoelectric substrate generates strain in the substrate, which is partially transferred to the nanomagnets and rotates the magnetizations of some of them away from their initial orientations. The rotated magnetizations remain in their new orientations after the field is removed, resulting in 'non-volatility'. In isolated nanomagnets, the magnetization rotates by <90° upon application of the electric field, but in a dipole-coupled pair consisting of one 'hard' and one 'soft' nanomagnet, which are both initially magnetized in the same direction by the magnetic field, the soft nanomagnet's magnetization rotates by [Formula: see text] upon application of the electric field because of the dipole influence of the hard nanomagnet. This effect can be utilized for a nanomagnetic NOT logic gate.


Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices.
A multiscale model of the cardiovascular system is presented. Hemodynamics is described by a lumped parameter model, while heart contraction is described at the cellular scale. An electrophysiological model and a mechanical model were coupled and adjusted so that the pressure and volume of both ventricles are linked to the force and length of a half-sarcomere. Particular attention was paid to the extreme values of the sarcomere length, which must keep physiological values. This model is able to reproduce healthy behavior, preload variations experiments, and ventricular failure. It also allows to compare the relevance of standard cardiac contractility indices. This study shows that the theoretical gold standard for assessing cardiac contractility, namely the end-systolic elastance, is actually load-dependent and therefore not a reliable index of cardiac contractility.


Determination of reaction volumes and polymer distribution characteristics of tobacco mosaic virus coat protein.
A method that allows the quantitative determination of reaction volumes from sedimentation velocity experiments in an analytical ultracentrifuge is presented. Combined with a second method for detecting pressure-induced depolymerization, general characteristics of polymer distributions may be probed. We show that it is possible to determine if a sample is in an equilibrium or metastable state of subunit association. Our approach to probe macromolecular aggregation systems by small pressure perturbations is not restricted to the use of centrifuges. This method has been applied to characterize certain aspects of the polymerization of tobacco mosaic virus coat protein (TMVP). There are at least two helical polymer conformations in RNA-free coat protein rods. The smaller, helix I, polymers are limited to sizes below about 70 subunits (four to five helical turns) and undergo some kind of cooperative conformational change before further subunits may be added indefinitely. In contrast to helix I, the larger helix II polymers occur as broader and skewed size distributions. Under moderately strong polymerization conditions, the equilibrium state can contain both types of helical rods. The reaction volume for the addition of trimers is -220 ml/mol for both types of helical polymers. These results are compared with the results of previous thermodynamic analyses of TMVP polymerization.


Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults.
Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.


The benefits of a simplified method for CPR training of medical professionals: a randomized controlled study.
We developed and tested a training method for basic life support incorporating defibrillator feedback during simulated cardiac arrest (CA) to determine the impact on the quality and retention of CPR skills. 298 subjects were randomized into 3 groups. All groups received a 2h training session followed by a simulated CA test scenario, immediately after training and at 3 months. Controls used a non-feedback defibrillator during training and testing. Group 1 was trained and tested with an audiovisual feedback defibrillator. During training, Group 1 reviewed quantitative CPR data from the defibrillator. Group 2 was trained as per Group 1, but was tested using the non-feedback defibrillator. The primary outcome was difference in compression depth between groups at initial testing. Secondary outcomes included differences in rate, depth at retesting, compression fraction, and self-assessment. Groups 1 and 2 had significantly deeper compressions than the controls (35.3 ± 7.6 mm, 43.7 ± 5.8 mm, 42.2 ± 6.6 mm for controls, Groups 1 and 2, P=0.001 for Group 1 vs. controls; P=0.001 for Group 2 vs. controls). At three months, CPR depth was maintained in all groups but remained significantly higher in Group 1 (39.1 ± 9.9 mm, 47.0 ± 7.4 mm, 42.2 ± 8.4 mm for controls, Groups 1 and 2, P=0.001 for Group 1 vs. control). No significant differences were noted between groups in compression rate or fraction. A simplified 2h training method using audiovisual feedback combined with quantitative review of CPR performance improved CPR quality and retention of these skills.


Multimodal therapy for liver cirrhosis patients with advanced hepatocellular carcinoma.
We have previously shown that continuous intra-arterial combination chemotherapy (IACC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with HCV-related liver cirrhosis (C-LC) or alcoholic liver cirrhosis (A-LC) than in patients with HBV-related LC (B-LC). However, it is still unknown whether IACC actually improves the prognosis of aHCC patients with liver cirrhosis (LC), because it is difficult to perform a randomized controlled trial for patients with a poor prognosis. The aim of this study was to retrospectively assess the influence of IACC on the prognosis of aHCC. Fifty-eight adult Japanese patients who had aHCC and LC underwent repeated trans-arterial chemoembolization (TACE) without IACC between 1990 and 1997 at our hospital (group T), while 43 patients with aHCC and LC received IACC between 2000 and 2008 after undergoing several TACE sessions (group R). The Japan Integrated Staging score (JIS score) of each patient was ≥ 3 at the time of presentation, except for patients with tumor thrombi involving the first or subsequent portal vein branches or those with tumor invasion of the inferior vena cava. The same IACC regimen was repeated for as long as possible in group R. In group T, 13 patients had B-LC, 37 patients had C-LC, and 8 patients had A-LC, while the respective numbers were 14, 21, and 8 in group R. The median survival time (MST) was 248 days for patients with C-LC in group T and 708 days for those in group R, while it was 253 days for patients with A-LC in group T and 593 days for those in group R. There were significant differences of survival between the two groups. However, MST was 369 days for patients with B-LC in group T and 782 days for those in group R, without a significant difference. In group R, a complete or partial response was achieved after 4 weeks of chemotherapy in 14.3% of patients with B-LC versus 42.9% of patients with C-LC and 37.5% of patients with A-LC. In LC patients with a JIS score > 3 at diagnosis, multimodal therapy with IACC after TACE prolongs the MST of C-LC or A-LC patients compared with TACE alone, although it does not improve the MST of patients with B-LC.


Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways.
It was shown recently that exposure of the developing rat brain during the peak of synaptogenesis to commonly used general anesthetics can trigger widespread apoptotic neurodegeneration in many regions of the developing rat brain and persistent learning/memory deficits later on in life. To understand the mechanism by which general anesthetics induce apoptotic neuronal death we studied two common apoptotic pathways--the intrinsic and the extrinsic pathway--at different time points during synaptogenesis. We found that the intrinsic pathway is activated early on during anesthesia exposure (within two hours), as measured by the down-regulation of bcl-x(L), up-regulation of cytochrome c and the activation of caspase-9 in 7-day-old rats (the peak of synaptogenesis), but remains inactivated in 14-day-old rats (the end of synaptogenesis). The extrinsic pathway is activated later on (within six hours of anesthesia exposure), as measured by the up-regulation of Fas protein and the activation of caspase-8 in 7-day-old rats, but remains inactivated in 14-day-old rats. Anesthesia-induced apoptotic neurodegeneration is age dependent with vulnerability closely correlating with the timing of synaptogenesis, i.e. the developing brain is most sensitive at the peak of synaptogenesis (7 days old) and least sensitive at the end of synaptogenesis (14 days old).


Does stroke location predict walk speed response to gait rehabilitation?
Recovery of independent ambulation after stroke is a major goal. However, which rehabilitation regimen best benefits each individual is unknown and decisions are currently made on a subjective basis. Predictors of response to specific therapies would guide the type of therapy most appropriate for each patient. Although lesion topography is a strong predictor of upper limb response, walking involves more distributed functions. Earlier studies that assessed the cortico-spinal tract (CST) were negative, suggesting other structures may be important. The relationship between lesion topography and response of walking speed to standard rehabilitation was assessed in 50 adult-onset patients using both volumetric measurement of CST lesion load and voxel-based lesion-symptom mapping (VLSM) to assess non-CST structures. Two functional mobility scales, the functional ambulation category (FAC) and the modified rivermead mobility index (MRMI) were also administered. Performance measures were obtained both at entry into the study (3-42 days post-stroke) and at the end of a 6-week course of therapy. Baseline score, age, time since stroke onset and white matter hyperintensities score were included as nuisance covariates in regression models. CST damage independently predicted response to therapy for FAC and MRMI, but not for walk speed. However, using VLSM the latter was predicted by damage to the putamen, insula, external capsule and neighbouring white matter. Walk speed response to rehabilitation was affected by damage involving the putamen and neighbouring structures but not the CST, while the latter had modest but significant impact on everyday functions of general mobility and gait. Hum Brain Mapp 37:689-703, 2016. © 2015 Wiley Periodicals, Inc.


Causal inferences as perceptual judgements.
We analyze how subjects make causal judgements based on contingency information in two paradigms. In the discrete paradigm, subjects are given specific information about the frequency a, with which a purported cause occurs with the effect; the frequency b, with which it occurs without the effect; the frequency c, with which the effect occurs when the cause is absent; and the frequency d, with which both cause and effect are absent. Subjects respond to P1 = a/(a + b) and P2 = c/(c + d). Some subjects' ratings are just a function of P1 while others are a function of delta P = P1-P2. Subjects' post-experiment reports are accurate reflections of which model they use. Combining these two types of subjects results in data well fit by the weighted delta P model (Allan, 1993). In the continuous paradigm, subjects control the purported causes (by clicking a mouse) and observe whether an effect occurs. Because cause and effects occur continuously in time, it is not possible to explicitly pair causes and effects. Rather, subjects report that they are responding to the rate at which the effects occur when they click versus when they do not click. Their ratings are a function of rates and not probabilities. In general, we argue that subjects' causal ratings are judgments of the magnitude of perceptually salient variables in the experiment.


DNA fingerprinting pattern and susceptibility to antifungal drugs in Cryptococcus neoformans variety grubii isolates from Barcelona city and rural environmental samples.
Cryptococcus neoformans var. grubii (serotype A) was isolated from 12 soil samples mixed with pigeon droppings (16.9%) from 71 soil samples in Barcelona and rural areas of Catalonia. C. neoformans was not isolated from indoor dust and Eucalyptus debris. PCR fingerprinting was performed in 22 representative isolates and all of them corresponded to the VNI pattern. Susceptibility testing for the 22 isolates of C. neoformans var. grubii showed that all of them were susceptible to amphotericin B. Three isolates presented MICs (Minimal Inhibitory Concentrations) > or = 1 microg/ml to Itraconazole, five MICs > or = 1 microg/ml to ketoconazole and four were fluconazole resistant, (MICs > or = 64 microg/ml), while three of them were shown to have MICs > or = 1 microg/ml to voriconazole. In spite that all isolates presented the same DNA fingerprinting pattern, the susceptibility to antifungals is very variable. The possibility of acquiring cryptococcosis infection with primarily resistant environment strains is feasible.


The role of platelets in blood coagulation--effects of platelet agonists and GPIIb/IIIa inhibitors studied by free oscillation rheometry.
We have studied the contribution of platelets to the coagulation of plasma and the effects of activation or inhibition of platelets on the coagulation process in unanticoagulated fresh whole blood (subsequently termed native blood). For this purpose, we have used a free oscillation rheometer (FOR), the ReoRox4, a new instrument that enables noninvasive viscoelastic measurements of clot formation in plasma and whole blood. Platelets appear essential for the initiation of coagulation if no activating surface is present. We prepared platelet-free plasma by quick centrifugation and filtration of native blood, which did not coagulate if stored in plastic containers at 37 degrees C but clotted if transferred to glass containers. Addition of platelet agonists, such as collagen or the thrombin receptor agonist peptide, SFLLRN, significantly accelerated the clotting of native blood and also changed the rheometer curve appearance, accelerating both onset and completion of clot formation (i.e. fibrin gel formation). Inhibition of platelet glycoprotein (GP) IIb/IIIa with the peptide-derived compound MK-852 or the antibody-derived abciximab (Reopro) prevented clot retraction and prolonged the clotting time with SFLLRN. In collagen-stimulated samples, MK-852 accelerated clotting but delayed completion of clotting while abciximab prolonged both clotting time and completion of clotting. To our knowledge, this is the first report showing that activation of platelets in native whole blood shortens the coagulation time ex vivo. It also describes a new instrument that enables studies of the viscoelastic properties of a forming whole blood clot.


[Contribution of polymorphic variants of the genes of xenobiotic transformation enzymes, antioxidative defense, and DNA repair to the development of individual predisposition to hepatobiliary and reproductive system diseases in petrochemical workers].
The paper gives the basic results of studying the polymorphic loci of the genes of xenobiotic transformation enzymes, antioxidative defense, and DNA repair in petrochemical workers. Polymerase chain reaction-restriction fragment length polymorphism assay was used to identify markers of the predisposition to the development of toxic hepatitis in men and impaired reproduction in women.


Novel isolates double the number of chemotrophic species and allow the first description of higher taxa in Acidobacteria subdivision 4.
Despite their high phylogenetic diversity and abundance in soils worldwide, Acidobacteria represent an enigmatic bacterial phylum. Four novel Acidobacteria strains were isolated from Namibian semiarid savannah soils using low-nutrient cultivation media and extended incubation periods. 16S rRNA gene sequence analyses placed the isolates within Acidobacteria subdivision 4. Sequence identities with their closest relatives Aridibacter famidurans and Blastocatella fastidiosa were ≤94.9%. The Gram-negative, non-motile, rod-shaped, aerobic, and chemoorganotrophic bacteria grew at minimum doubling times of 5-14h and formed tiny white to pinkish colonies. Major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, and phosphatidylglycerol. The major isoprenoid quinone was MK-8. The major fatty acid methyl esters comprised iso-C15:0, iso-C15:1H/C13:0 3-OH, and C16:1ω7c/C16:1ω6c. Based on a polyphasic taxonomic characterization, strain Ac_18_E7(T) (=DSM 26557(T)=LMG 28656(T)) represented a novel species and genus, Tellurimicrobium multivorans gen. nov., sp. nov. The other strains constituted three independent species of the novel genus Stenotrophobacter gen. nov., Stenotrophobacter terrae sp. nov. (Ac_28_D10(T)=DSM 26560(T)=LMG 28657(T)), S. roseus sp. nov. (Ac_15_C4(T)=DSM 29891(T)=LMG 28889(T)), and S. namibiensis sp. nov. (Ac_17_F2(T)=DSM 29893(T)=LMG 28890(T)). These isolates doubled the number of established species and permitted the description of higher taxa of Acidobacteria subdivision 4. The family Blastocatellaceae fam. nov. is proposed in order to summarize the currently known oligotrophic, slightly acidophilic to neutrophilic mesophiles from arid soils. The superordinated order Blastocatellales ord. nov. and Blastocatellia classis nov. also include the terrestrial species Pyrinomonas methylaliphatogenes and the anoxygenic photoheterotrophic species Chloracidobacterium thermophilum from microbial mats.


Wolff-Parkinson-White syndrome presenting in atrial fibrillation.
A case of atrial fibrillation in a patient with Wolff-Parkinson-White (WPW) syndrome is presented. In this case, the patient's ECG initially was misread as ventricular tachycardia. The therapy was appropriate for the actual condition, although electrical cardioversion and defibrillation eventually were required. The treatment of WPW with atrial fibrillation in this case consisted of lidocaine and procainamide. Verapamil, propranolol, and digoxin, which normally are indicated for WPW with tachyarrhythmias, are contraindicated for WPW with atrial fibrillation.


The mitochondrial K(ATP) channel--fact or fiction?
The mitochondrial ATP-dependent K(+) channel (mitoK(ATP)) is widely considered by many to play a central role in cardioprotection by ischemic and pharmacological preconditioning and by ischemic postconditioning. Nevertheless, several laboratories have questioned the existence of mitoK(ATP). This article summarizes the evidence for and against and addresses two key questions: How strong is the evidence for the presence of a K(ATP) channel in mitochondria? Are the pharmacological agents used to modulate mitoK(ATP) activity sufficiently specific to allow the role of these channels in cardioprotection to be established?


Considerations for carcinogenesis countermeasure development using mouse models.
Activities in space will expose humans to profoundly new environments, challenging human performance and will require innovative supportive technologies. Among these environmental variables, exposure to ionizing radiation is a major concern for astronauts, as the long-term effects of exposure on diverse tissues are poorly understood. This need however creates opportunities for novel approaches, particularly in the development of countermeasures against the effects of ionizing radiation exposure. Carcinogenesis presents a unique challenge as a disease process, due to the inherent complexities of the process and the challenges of obtaining a large volume of clinical evidence. Thus, developing the countermeasures to address potential effects of ionizing radiation exposure will require understanding biological underpinnings to design countermeasures effectively in conjunction with highly robust modeling approaches to test and examine in vivo. This review will highlight specific considerations for accelerated development of space radiation countermeasures against carcinogenesis.


Effect of pimozide on the cytology of the eel pituitary. I. Prolactin-secreting cells.
Pimozide, a specific blocker of dopaminergic receptors, was injected for 4 to 9 days in freshwater (FW) eels or eels acclimated to sea water (SW), for 10 to 30 days. The daily dose was 100 or 200 microgram/100 g. In FW, pimozide induces a nuclear hypertrophy in the prolactin (PRL) cells of eels; these elongated cells increase in height. The amount of erythrosinophilic granules in the cytoplasm, initially reduced, increases. Plasma electrolyte values are not modified: only the plasma sodium level slightly rises with the higher dose. In SW, PRL cells appear less active. After 10 days, this hypoactivity is not yet fully evident; pimozide stimulates PRL cells without affecting electrolyte values. After 1 month in SW, PRL cells are stimulated with pimozide and a slight regranulation may occasionally occur. The response in SW is never as marked as it is in FW; a high dose is not more effective than a low one. The higher dose significantly raises Na+, Ca2+ and Cl- plasma levels. These data suggest that prolactin synthesis and release increase with pimozide. They corroborate the hypothesis of a hypothalamic inhibitory control on PRL secretion mediated through dopaminergic fibers in the eel, but other factors may also be involved in this regulation in addition to the effect of salinity.


Rapid high performance liquid chromatography method for erlotinib quantification in vitro: Application to study the effect of resveratrol on metabolism and cellular uptake of erlotinib.
Erlotinib is a selective epidermal growth factor receptor inhibitor that is used for the treatment of non-small cell lung cancer and pancreatic cancer. Its metabolism is mainly mediated by cytochrome P450 3A (CYP 3A). Resveratrol, a natural compound found in many plants and supplements, is known to inhibit CYP3A enzyme, therefore, it may act as an inhibitor for the metabolism of erlotinib. Development of a rapid high performance liquid chromatography with photodiode array detection (HPLC-PDA) method for the quantification of erlotinib in liver microsomes and cancer cells and its application to study resveratrol effect on metabolism and cellular uptake of erlotinib. HPLC-PDA was used to develop an efficient bioanalytical method with a 2.5-min runtime preceded by a simple protein precipitation step. The method was validated according to the European Medicines Agency guidelines. Erlotinib metabolic stability and resveratrol effect on erlotinib metabolite formation were evaluated in rat liver microsomes. Furthermore, the method was used to measure the intracellular concentrations of erlotinib in cancer colorectal cells and investigating resveratrol effect on the cellular uptake of erlotinib. A rapid HPLC-PDA method was developed and validated for the first time to address potential drug interaction of erlotinib with resveratrol. Resveratrol was a strong inhibitor of erlotinib metabolism in vitro with IC50 = 4.03 μM. Resveratrol, however, had no effect on erlotinib cellular uptake after 1 h incubation in human colorectal cancer cells. The study suggests that resveratrol may produce a potential herb-drug interaction with erlotinib at the metabolism level and should be investigated in patients in the clinic.


Work-related thumb pain in physiotherapists is associated with thumb alignment during performance of PA pressures.
Pain is common in the thumbs of physiotherapists. The purpose of this observational study was to investigate whether there is an association between the alignment of the thumb during performance of postero-anterior (PA) pressures and the presence of thumb pain. One hundred and twenty-nine physiotherapists who attended the Musculoskeletal Physiotherapy Association Conference (2003) participated. After providing a history of any work-related thumb pain, participants applied a PA pressure mimicking the technique they would use on a cervical spine, while the position of their metacarpophalangeal (MP) and interphalangeal (IP) joints was photographed. There was an association (p<0.05) between work-related thumb pain and alignment of the thumb during performance of PA pressures: participants who were able to maintain their MP and IP joints in extension were less likely to report pain. These findings serve as a guide to the safe performance of mobilization techniques, both for beginning practitioners and for experienced therapists complaining of thumb pain.


Axonal neuropathy with monoclonal IgG kappa that binds to a neurofilament protein.
We report a 74-year-old woman with a slowly progressive sensory motor axonal neuropathy and a monoclonal IgG-kappa that bound to a 68-kd axonal protein identified as the low molecular weight neurofilament protein. The sera of control subjects and disease controls did not bind to neurofilament protein.


The Mitral Coaptation to Ventricular Septal Space: Two- and Three-Dimensional Transesophageal Echocardiographic Assessment.
To assess the dimensions and changes in the CSEPT (space between the ventricular septum and mitral coaptation point) before and after cardiopulmonary bypass (CPB) and to compare patients with and without aortic valve stenosis (AS) undergoing cardiac surgery. Retrospective review of intraoperative transesophageal echocardiographic examinations. Single academic medical center. The study comprised 91 elective cardiac surgical patients-30 with AS scheduled for aortic valve replacement and 61 without AS (non-AS). Two- and 3-dimensional (2D and 3D) analysis of the CSEPT before and after CPB. Assessment of the CSEPT distances and areas was performed using 2D and 3D imaging before and after CPB. Two-dimensional measures of CSEPT distances were performed using midesophageal 5-chamber and long-axis windows. Three-dimensional measures were performed offline using multiplanar reconstruction. The CSEPT space was smaller after CPB (p < 0.01). Before and after CPB, the midesophageal 5-chamber and long-axis windows were similar to each other, and both were larger than the pre-CPB 3D CSEPT distance. Patients with AS had smaller before and after CPB distances and areas compared with non-AS patients (p < 0.05). The change in CSEPT area in AS patients was 24%. The CSEPT space is smaller after CPB and more so for patients with AS undergoing aortic valve replacement. Two-dimensional CEPT distances vary compared with 3D CSEPT distances. Additional study using Doppler analysis will elucidate the added value of 3D assessment of the CSEPT space.


Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid.
Cytomegalovirus (CMV) infection can cause severe pulmonary disease in immunocompromised patients. There are no standard diagnostic criteria for CMV pulmonary disease beyond histopathology findings on lung tissue, which is challenging to obtain in pediatric patients. Bronchoalveolar lavage (BAL) fluid is easier to obtain. Since CMV remains latent after primary infection and can potentially reactivate due to any inflammatory response, CMV detection in BAL specimen may not indicate acute CMV pulmonary disease. Thus, we describe the clinical manifestations and outcomes of pediatric patients with CMV detection in BAL fluid. We reviewed the clinical, radiologic, and laboratory data of patients <19 years old with a BAL specimen positive for CMV during a 5-year period. Thirty-four encounters in 29 patients were found with CMV detected in their BAL specimen. Half (17/34) of the encounters were in immunocompromised patients. CMV, polymerase chain reaction (PCR) was the most common positive test. Forty-seven percent of the patients had other infections detected in BAL specimens. The majority of patients were never treated for CMV and resolved their acute respiratory illness. Only one patient had probable CMV pulmonary disease. CMV is frequently recovered from BAL specimens but does not usually indicate acute CMV pulmonary disease. We would suggest that other diagnoses be considered first, even if CMV is recovered. Pediatr Pulmonol. 2017;52:112-118. © 2016 Wiley Periodicals, Inc.


Pharmacokinetics of Amonafide in dogs.
Amonafide, one of a series of imide derivatives of 1,8-naphthalic acid synthesized by Brana et al. has shown significant antitumor activity against a variety of experimental tumors, including L1210 leukemia and P388 leukemia. Along with the clinical trial at our institute, we have studied the disposition of Amonafide in dogs by HPLC and fluorometry. Six dogs received Amonafide i.v. at 5 mg/kg (100 mg/m2) over 15 min; three were sacrificed at 6 h, and three at 24 h. The initial plasma t1/2 of Amonafide was 2.4 +/- 0.4 min, the intermediate t1/2, 26.8 +/- 3.7 min, and the terminal t1/2, 21.7 +/- 4.0 h. The peak plasma concentration achieved was 6.3 +/- 1.7 micrograms/ml. The average apparent volume of distribution was 12.84 +/- 0.54 1/kg, and the total clearance was 0.56 +/- 0.16 1/kg/h. In 24 h, 9.5% +/- 0.2% of the administered dose was excreted in the urine as the parent drug, and 7.4% +/- 1.4% in the bile in 6 h. Amonafide penetrated the CSF readily and achieved the highest concentration 20-25 min after administration, which was 30% of the concurrent plasma level. Amonafide underwent extensive metabolism to at least three major metabolites and two or more minor metabolites. The alpha and beta plasma t1/2 of the major metabolite, an N-oxide derivative, were 24.8 min and 28.6 h, respectively. The 24-h cumulative urinary excretion was 1.4% of the injected dose, and the cumulative biliary excretion was 16.7% in 6 h. At autopsy 6 h after dosing, the liver contained the highest percentage (0.23% of administered dose) of unchanged Amonafide, followed by the stomach (0.11%), lung (0.04%), kidney (0.04%), and pancreas (0.03%). The rest of the major organs retained less than 0.02% of the Amonafide dose. One day after dosing, no detectable amount of Amonafide was found in any of these tissues, indicating that Amonafide appears to be extensively metabolized and not significantly retained in the dog.


Volatilization of components from and water absorption of polyether impressions.
To evaluate the accuracy of stone dies produced from impressions with polyether impression materials and a vinyl polysiloxane reference material after prolonged storage at 0, 50, or 100% relative humidity. Impressions were taken with light and heavy-bodied types of the polyethers P2 (P2L/H; Heraeus Kulzer) and Impregum (IML/H; 3M ESPE) and vinyl polysiloxane Flexitime (FLL/H; Heraeus Kulzer) from a truncated steel master cone in cylindrical trays giving 4 mm layer thickness at the prominence line. Impressions were taken at 23 degrees C, and stone dies were poured after 1, 2, 3, 4, or 5 days storage at 23 degrees C and 0, 50, or 100% RH. Accuracy was determined as discrepancy between a steel ring with accurate fit on the master cone and the stone die and expressed as base diameter deviation Deltad (microm). One-way ANOVA and Duncan's post-hoc test were used for statistical data analysis (p<0.05). P2L/H showed significant Deltad increase (30-240 microm) depending on storage time and humidity (p<0.05). Dies from IML/H at 0% RH were 90 through 180 microm enlarged, at 50% RH the maximum diameter increase was 60 microm, and at storage in 100% RH all dies were 25-120 microm smaller (p<0.05). Dies from FLL/H showed maximum Deltad deviations (55 to -10 microm). P2 impressions release volatile substances during storage and should preferably be poured within less than 24 h. Impregum absorbs water and should be stored at <50% humidity. The accuracy of Flexitime is scarcely affected by storage time or by ambient humidity.


Increased frequency of spontaneous and X-ray-induced chromosomal aberrations in lymphocytes from neonates and the influence of caffeine--an in vitro study.
We have examined lymphocytes from human preterm (PT) and fullterm (FT) babies for an effect of gestational age (GA) on chromosomal aberrations either occurring spontaneously or induced by treatment with X-rays (1 Gy) alone; or with caffeine (1,3,7-trimethylxanthine) supplementation (5 X 10(-4) M), in comparison to the lymphocytes of healthy adults (AD). Percent of abnormal cells (%Abn) was used as an indicator of chromosome sensitivity to the different treatments. PT babies had significantly higher spontaneous and X-ray-induced %Abn values than AD, but were comparable to FT. After X-irradiation + caffeine the yield of aberrations in any 2 groups was not significantly different. Chromosomal sensitivity may result from factors other than GA. This in vitro model may permit study of the mechanisms of chromosomal damage repair and prevention of free radical damage of DNA during the perinatal period.


Direct correlation between sonography and histology of minute malignant hepatic nodule.
To improve the qualitative diagnosis of ultrasonography (US) of minute malignant hepatic nodules, we studied the accurate and direct correlations between US and histopathology of 33 lesions using formalin-fixed autopsied livers. The target nodules were cut on the same plane as their US-image. The solid nests of malignant tumor without degeneration were hypoechoic on US. Hepatocellular carcinoma showed a wide variety of echo levels, from hypoechoic to isoechoic, and its images were more heterogeneous than those of other malignant lesions. The squamous cell carcinoma ranged from hypoechoic to hyperechoic according to the degree of keratinization. US may be useful for evaluating the degree of differentiation in squamous cell carcinoma. Marked mucin-production and "comedo" pattern seem to be histological factors of the hyperechoic US image of adenocarcinoma. This study may contribute to improve the quality of US-diagnosis of minute hepatic nodular lesions.


Dietary zinc enrichment reduces the cadmium burden of mealworm beetle (Tenebrio molitor) larvae.
The industrial production of Tenebrio molitor L. requires optimized rearing and processing conditions to generate insect biomass with high nutritional value in large quantities. One of the problems arising from processing is a tremendous loss in mineral accessibility, affecting, amongst others, the essential trace element Zn. As a feasible strategy this study investigates Zn-enrichment of mealworms during rearing to meet the nutritional requirements for humans and animals. Following feeding ZnSO4-spiked wheat bran substrates late instar mealworm larvae were evaluated for essential micronutrients and human/animal toxic elements. In addition, growth rate and viability were assessed to select optimal conditions for future mass-rearing. Zn-feeding dose-dependently raised the total Zn content, yet the Znlarvae/Znwheat bran ratio decreased inversely related to its concentration, indicating an active Zn homeostasis within the mealworms. The Cu status remained stable, suggesting that, in contrast to mammals, the intestinal Cu absorption in mealworm larvae is not affected by Zn. Zn biofortification led to a moderate Fe and Mn reduction in mealworms, a problem that certainly can be overcome by Fe/Mn co-supplementation during rearing. Most importantly, Zn feeding massively reduced the levels of the human/animal toxicant Cd within the mealworm larvae, a technological novelty of outstanding importance to be implemented in the future production process to ensure the consumer safety of this edible insect species.


Insulin improves well-being for selected elderly type 2 diabetic subjects.
The effects of insulin therapy on patient well-being, treatment satisfaction and mood, and on carer strain were studied in 30 elderly Type 2 diabetic patients (age 73 +/- 7 (SD) yr) in poor glycaemic control on tablet therapy. A comparison group of ten poorly controlled patients who remained on oral agents was also studied. After 4 weeks of insulin treatment, there were significant improvements in mental health, role-emotional, role-physical (all P<0.05) and vitality (P<0.01) domains of the short form health survey (SF-36), and also in the diabetes treatment and satisfaction questionnaire (DTSQ) and geriatric depression scale (both P<0.01) compared to baseline. After 12 weeks, the improvements in mental health, social functioning and vitality (P<0.01 for all domains), and in the DTSQ were sustained. Carer strain was lower at 4 weeks. No changes in outcomes were seen in the comparison group. In selected elderly Type 2 diabetic patients, insulin treatment is associated with significant improvements in well-being, treatment satisfaction and mood, even without significant improvements in glycaemic control and without increase in carer strain. The SF-36 and DTSQ are sensitive to the benefits of the changes in the treatment for these patients.


Phospholipid metabolism is required for M1 muscarinic inhibition of N-type calcium current in sympathetic neurons.
The signal transduction cascade mediating muscarinic receptor modulation of N-type Ca2+ channel activity by the slow pathway has remained incompletely characterized despite focused investigation. Recently we confirmed a role for the G-protein Gq and identified phospholipase C (PLC), phospholipase A2 (PLA2), and arachidonic acid (AA) as additional molecules involved in N-current inhibition in superior cervical ganglion (SCG) neurons by the slow pathway. We have further characterized this signal transduction cascade by testing whether additional molecules downstream of phosphatidylinositol-4,5-bisphosphate (PIP2) are required. The L-channel antagonist nimodipine was bath-applied to block L-current. Pretreating cells with pertussis toxin (PTX) minimized M2/M4 muscarinic receptor inhibition of N-current by the membrane-delimited pathway. Consistent with our previous studies, pharmacologically antagonizing M1 muscarinic receptors (M1Rs), Gqalpha, PLC, PLA2, and AA minimized N-current inhibition by the muscarinic agonist oxotremorine-M (Oxo-M). When cells were left untreated with PTX, leaving the membrane-delimited pathway intact and the same antagonists retested, Oxo-M decreased whole cell currents. Moreover, inhibited currents displayed slowed activation kinetics, indicating intact N-current inhibition by the membrane-delimited pathway. These findings indicate that the antagonists used to block the slow pathway acted selectively. PLA2 cleaves AA from phospholipids, generating additional metabolites. We tested whether the metabolite lysophosphatidic acid (LPA) mimicked the inhibitory actions of Oxo-M. In contrast to AA, applying LPA did not inhibit whole cell currents. Taken together, these findings suggest that the slow pathway requires M1Rs, Gqalpha, PLC, PIP2, PLA2, and AA for N-current inhibition.


Synthesis and anti-HIV activities of symmetrical N1,N3-dibenzyl-2-hydroxy-propane derivatives.
We report the synthesis and the anti-HIV activities of new C2-symmetrical and achiral N1,N3-dibenzyl-2-hydroxy-propane isosteres. Some of them showed significant inhibitory activity with respect to HIV-infected MT4 cells (compound 6a and 7a, IC50 = 0.1 microM). These new structurally simple compounds represent new synthons which can be suitable for combinatorial chemistry purposes.


Genomic integrity of the Y chromosome sequence-tagged-sites in infertile and Down syndrome Jordanian males.
The long arm of the Y chromosome contains nonoverlapping regions termed azoospermia factor (AZF) with great influence on male fertility. Microdeletions at these regions minimise the males' ability to father offsprings. In this preliminary study, we attempted to screen the presence or absence of twenty Y chromosome's sequence-tagged sites (STS) associated with fertility in infertile and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22 karyotyped DS males was extracted and amplified in multiplex polymerase chain reaction (PCR) containing 20 primer pairs that amplify Y-specific STS that cover functional regions associated with AZF and spermatogenesis-related genes. Our results indicated the integrity of the Y chromosome at the 20 fertility markers for both the fertile and Down syndrome males. However, the results of the infertile males showed the presence of microdeletions at these Y-specific STS. Three samples showed Y chromosome microdeletion when blood and seminal fluid genomic DNA were assayed, while two samples showed microdeletion only when seminal fluid genomic DNA was assayed. The current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases. Furthermore, our results indicate the importance of genetic counselling in managing infertility cases.


Mobile, Population-wide, Hybrid HIV Testing Strategy Increases Number of Children Tested in Rural Kenya and Uganda.
Efficient ways to identify children with HIV in the context of universal test-and-treat policies are needed. We evaluated a hybrid testing strategy combining mobile community and home-based HIV testing in 87,700 children across 32 rural communities in 2 East African countries. This approach resulted in 81% testing coverage of at-risk children and doubled the number of children diagnosed with HIV.


Population structure of the rare damselfly, Ischnura gemina (Kennedy) (Odonata: Coenagrionidae).
The population structure of the endemic San Francisco Bay Area damselfly, Ischnura gemina, is examined using mark-recapture methods. Average daily movements, sex ratios, population size, maturation times, survivorship, and dispersion patterns, were recorded and calculated from two small (each less than one hectare) sites 150 m apart in Glen Canyon, San Francisco. Of 563 adults marked over 36 days, 412 (73%) were recaptured at least once. Average daily movements for males and females were less than 6 m, suggesting local movements. However, directional movements of 150 m were observed from one site to the other, indicating dispersal potential. One of the populations was a satellite composed entirely, of emigrating individuals from the other site; no larvae or teneral adults were found at the satellite area. Males were more aggregated than females at both sites. Both sexes were highly clumped at one site but were nearly randomly dispersed at the other site. Total population size for both sexes tended to be constant throughout the sampling period, at about 250. Adult population estimates showed more males were present than, females, but larval counts at one site indicated only a slight excess of males. Average life span estimates ranged from 6.5 days (females) to 23.3 days (males). One male lived at least 36 days. Maturation time for males was about 5-7 days, 7-10 days for females. A long life span and long flight season (March to November) are probably adaptations to the foggy San Francisco climate. All populations of I. gemina located to date are small, possibly originating from founders from nearby demes, and may be subject to different selection pressures. The dispersal potential of I. gemina may increase its chance of survival should small urban demes be threatened with destruction.


Patient labels as a quality indicator of identitovigilance in French hospitals.
Identity risk is frequent and serious. Between 2007 and 2010, 25.6% of 1572 serious adverse events declared in France are related to identitovigilance. No regulation clearly defines an ideal patient label even when a delivery refusal is applied in case of absent or incomplete identity (absence of surname and/or first name and/or birth date). The aim of the study was to draw up the current situation of patient labels in hospitals connected with our blood transfusion center and being used for blood products delivery and immuno-hematology analyses. We defined an ideal label with 5 items which must be present and clearly identified: surname, usual or marital name, first name, birth date and sex. It contains also an identifier, if possible with a bar code. We compare it with labels used in our hospitals. Only 22% (17/76) had a patient label in compliance with our ideal label. Most of the items, even if they were not clearly identified on the label, were present. The surname was present and clearly indicated in 75% of cases (57/76). In approximately 50% of cases, there was a barcoded permanent and/or stay identifier. Our results, with only 22% of labels considered as 'ideal', show all the work which remains to be done. A temporary solution can be the elaboration by hospitals of an identification guide of their present labels.


Long-Term Neurological Sequelae and Disease Burden of Japanese Encephalitis in Gansu Province, China.
The study aimed to evaluate the long-term neurological sequelae and the disease burden of JE in Gansu, China. JE patients were included as study population from 2005-2011 in Gansu, and a follow-up survey was conducted in 2007-2014. Pair-matched healthy individuals were selected as controls. All subjects underwent a neurological examination and intelligence quotient (IQ) and memory quotient (MQ) assessments. Then, the disability-adjusted life years (DALYs), and direct and indirect medical expenses were systematic assessed. Forty-four point seven percent of the JE patients had objective neurological deficits, compared with 2.4% of controls. Subnormal intelligence was found in 21.2% of JE subjects, compared with 1.2% control who exhibited a mildly reduced IQ. Abnormal MQ scores were noted in 56.3% JE subjects, compared with only 12.7% controls. Prevalence of each sequelae caused by JE were significantly higher in adults than in younger subjects. Furthermore, median DALY lost due to JE was 9.2 per subject. Median economic cost of JE was approximately $2776.6 per subject and significantly higher in adults than in younger subjects. JE patients suffered from severe neurological sequelae and high disease burden, resulting in a significant downstream burden for both the patients (especially adults) and the healthcare system.


Hepatitis-B-antigenemia with panarteritis, diffuse proliferative glomerulitis and malignant hypertension.
Fatal, rapidly progressive malignant hypertension, progressive renal failure and radiographic evidence of diffuse angitis, with persistent hepatitis-B-antigenemia, in a young man during his early recovery from documented type B viral hepatitis, is presented. At postmortem there was both light and electron microscopic evidence of systemic arteritis and proliferative glomerulonephritis.


A modified sublay-keyhole technique for in situ parastomal hernia repair.
The surgical treatment of a parastomal hernia is always challenging due to the high incidence of recurrence following primary repair, or stoma relocation and severe morbidities in prosthetic repair with polypropylene materials. We therefore developed a modified sublay-keyhole technique employing a polypropylene material to minimize the associated high risk of the procedure. We herein describe our initial clinical experience with this modified procedure. A retrospective review was performed to obtain the clinical data for 11 patients with parastomal hernias who underwent the modified in situ Sublay-keyhole repair from November 2008 to August 2010. The mean hernia size was 58.7 cm(2) (range 30-96 cm(2)), with an average polypropylene mesh size of 376.3 cm(2) (range 270-464 cm(2)). The mean length of the operation was 147.9 min (range 120-195.0 min), and the mean postoperative hospital stay was 11 days (range 9-14 days). All patients had an uneventful incisional recovery, with no infections. Two seromas and one hematoma were found and treated with conservative management, such as with aspiration, physical therapy and compression. All patients had been followed up, with a mean length of follow-up of 23.5 months (range 11-39 months). One parastomal hernia recurrence was seen 11 months postoperatively. Breakdown of the sutures and an over-sized aperture cut in the mesh were detected as the causes of the recurrence during the secondary repair procedure. Only re-sutures in both the mesh aperture and myofascial dehiscence were executed for this patient, and no re-recurrence was observed during an additional follow-up of 15 months. No recurrence of the parastomal hernia or presentation of an incisional hernia was detected during the follow-up. The modified Sublay-keyhole repair appears to be an effective procedure for parastomal hernias, with a low incidence of recurrence and risk of morbidities. Collection of more cases and further follow-up examinations will be needed to confirm our findings.


Analyzing trends in the spatial-temporal visitation patterns of mainland Chinese tourists in Sabah, Malaysia based on Weibo social big data.
Conducting on-site surveys to assess tourists' spatial visitation patterns and preferences is both time and labor intensive. However, an assessment of regional visitation patterns based on social media data can be an important decision-making tool for tourism management. In this study, an assessment of the visitation patterns of Chinese mainland tourists in Sabah is conducted to identify high-visitation hotspots and their changes, as well as large-scale and small-scale temporal characteristics. The data is sourced from the Sina Weibo platform using web crawler technology. In this work, a spatial overlay analysis was used to identify the hotspots of Chinese tourists' visits and the spatial and temporal variations. The results of the study revealed that the hotspots visited by Chinese tourists prior to 2016 have shifted from the southeast coast of Sabah, to the west coast of Sabah. At a small scale, Chinese tourists' visitation hotspots were mainly concentrated in the urban area along the southwest coast of Kota Kinabalu, shifting to the southeast of the urban area in 2018. This study provides insights into the applicability of social media big data in regional tourism management and its potential to enhance fieldwork.


Methods for Assessing Students' Learning of Histology: A Chronology Over 50 Years!
Over the past 50 years technology has made teaching and learning more interesting and has been a useful tool to motivate students to learn.Students today can learn using computers, iPads and mobile devices to access increasing numbers of educational websites and many eLearning apps. E-learning is now an integral component of most teaching delivery. There have been many innovations utilising both technology-enhanced and interactive learning strategies to revolutionise histology teaching. Now learning resources can be successfully delivered via the Internet, so students can complete all learning outcomes away from the traditional histology classroom environment (i.e. study histology online).The rapid developments in technologies and computer-based learning opportunities coincided with the appearance of Teaching and Learning Centres in Universities promoting teaching practices and supporting more improved learning strategies.This chapter describes how assessments in histology have become an important tool for student learning. A chronological documentation of various assessment opportunities enabled by the increasing use of technology will be described. In particular, assessment packages that engage students and return immediate feedback make histology learning efficient and significantly improve students' performance on examinations.Assessment strategies described here may be useful for "early career" histology teachers engaging eLearning and/or new teaching departments at new universities embarking on presenting curricula in newly established medical, dental and biomedical/health science programmes.This chapter is also an historical account of at least some assessment practices in histology over the past 50 years. Perhaps similar practices were used to assess student learning in other closely related disciplines such as anatomy including neuroanatomy.


Neuropsychophysical optimization by REAC technology in the treatment of: sense of stress and confusion. Psychometric evaluation in a randomized, single blind, sham-controlled naturalistic study.
The aim of this study is to investigate the effects of neuropsychophysical optimization (NPPO) protocol treatment by radioelectric asymmetric conveyer (REAC) technology in the management of sense of stress and confusion (SSC); an analysis of a single cluster of the psychological stress measure (PSM) test. The PSM, a self-administered questionnaire, was used to measure psychological stress and SSC for a group of 888 subjects. Data were collected immediately prior to and following the 4-week REAC-NPPO treatment cycle. This study demonstrates a significant reduction in scores measuring subjective perceptions of stress for subjects treated with one cycle of REAC-NPPO. At the end-point of the study, the number of treated subjects reporting symptoms of stress-related SSC on the PSM test was significantly reduced, whereas there was no difference in sham-treated subjects. One cycle of REAC-NPPO appears to reduce subjective perceptions of SSC measured by the PSM. This trial has been registered in the Australian New Zealand Clinical Trials Registry as ACTRN12607000497404.


Prevalence of physical activity among adults in a metropolitan Nigerian city: a cross-sectional study.
Baseline information on physical activity is relevant to controlling the epidemic of chronic noncommunicable diseases occurring in many African countries. However, standardized data on physical activity are lacking in Nigeria. We assessed the prevalence of physical activity and its relationships with sociodemographic characteristics in a subnational sample of Nigerian adults. A cross-sectional survey was conducted among a representative sample of 934 adults (age, 20-82 years) living in metropolitan Maiduguri, Nigeria. Physical activity was measured using the validated Nigerian version of the International Physical Activity Questionnaire (Hausa IPAQ-SF). Using the World Health Organization (WHO) guideline, participants were classified as sufficiently active or insufficiently active. Sociodemographic correlates of sufficient physical activity were identified using multinomial logistic regression. Overall, 68.6% of Nigerian adults were sufficiently active. There was no significant difference (P > 0.05) in prevalence of physical activity between men (68.0%) and women (69.3%), but physical activity tended to decrease with increasing age category, especially among men. Physical activity prevalence was positively associated with being married (OR = 1.52, CI = 1.04-4.37) and blue collar work (OR = 2.19, CI = 1.16-4.12) and negatively associated with car ownership (OR = 0.38, CI = 0.17-0.86) and higher income (OR = 0.54, CI = 0.10-0.95). The prevalence of physical activity varied between sociodemographic subgroups of Nigerian adults; thus, public health policies and interventions based on ecologic models of health behaviors may be warranted in promoting physical activity in Nigeria.


[Outpatient pediatric care during the COVID-19 pandemic with special emphasis on screening examinations and immunizations].
The COVID-19 pandemic has greatly changed the utilization of ambulatory medical care. Studies indicate that this also includes a decrease in pediatric prevention services. The aim of the study was to determine how the utilization of pediatric prevention services, in particular screening examinations and immunizations, developed over the course of the first pandemic wave until the end of September 2020 compared with the years 2015 to 2019. A data analysis based on nationwide statutory medical claims data from the first quarter of 2015 to the third quarter of 2020 was conducted. All treatments of patients aged 0 to 17 years were included and the quarterly case numbers compared on an annual basis. By considering trends and seasonality, preventive and curative treatment cases were modelled as a time series and compared to their expected values. No decreases in the quarterly numbers of screening examinations or immunizations were observed in 2020. In contrast, the number of curative pediatric cases decreased significantly in the second and third quarters of 2020 compared with the same periods of the previous years. Since there was no drop in the number of screening examinations, it should be assumed that the health problems addressed in this framework are detected in a timely manner despite the COVID-19 pandemic. However, since screenings do not cover all age groups, further investigation should be conducted to determine the health consequences of the observed decrease in curative cases.


Liquid biopsy in the management of advanced lung cancer: Implementation and practical aspects.
Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. In recent years, the discovery of actionable molecular alterations has changed the treatment paradigm of the disease. Tissue biopsies have been the gold standard for the identification of targetable alterations but present several limitations, calling for alternatives to detect driver and acquired resistance alterations. Liquid biopsies reveal great potential in this setting and also in the evaluation and monitoring of treatment response. However, several challenges currently hamper its widespread adoption in clinical practice. This perspective article evaluates the potential and challenges associated with liquid biopsy testing, considering a Portuguese expert panel dedicated to thoracic oncology point of view, and providing practical insights for its implementation based on the experience and applicability in the Portuguese context.


Impact of Portal Hypertension on Adverse Events after Splenic Arterial Aneurysm Embolization.
To evaluate the outcomes of splenic artery aneurysm (SAA) embolization and compare adverse event (AE) rates after embolization in patients with and without portal hypertension (PHTN). A retrospective review of all patients who underwent embolization of SAAs at 2 institutions was performed (34 patients from institution 1 and 7 patients from institution 2). Baseline demographic characteristics, preprocedural imaging, procedural techniques, and postprocedural outcomes were evaluated. Thirty-day postprocedural severe and life-threatening AEs were evaluated using the Society of Interventional Radiology guidelines. Thirty-day mortality and readmission rates were also evaluated. t test, χ2 test, and/or Fisher exact test were used for the statistical analysis. There was no statistically significant difference between patients with and without PHTN in the location, number, and size of SAA(s). All procedures were technically successful. There were 13 (32%) patients with and 28 (68%) patients without PHTN. The 30-day mortality rate (31% vs 0%; P = .007), readmission rates (61% vs 7%; P < .001), and severe/life-threatening AE rates (69% vs 0%; P < .001) were significantly higher in patients with PHTN than in those without PHTN. There was a significantly higher mortality and severe/life-threatening AE rate in patients with PHTN than in those without PHTN. SAAs in patients with PHTN need to be managed very cautiously, given the risk of severe/life-threatening AEs after embolization.


Aromatase inhibitors and the endometrium.
To investigate the potential impact of aromatase inhibitors, given after stopping tamoxifen treatment, on the endometrium of postmenopausal breast cancer patients. Review of all available literature of studies on aromatase inhibitor therapy in postmenopausal breast cancer patients previously treated with tamoxifen. (1) Endometrial thickness was found to be significantly lower in patients switched from tamoxifen treatment to aromatase inhibitor therapy, compared to those who continued tamoxifen treatment. This significant difference between the 2 groups was maintained throughout the entire treatment. (2) Vaginal bleeding was significantly more common in patients who continued tamoxifen therapy as compared to those who switched to aromatase inhibitors. (3) Replacement of tamoxifen treatment by aromatase inhibitors in postmenopausal breast cancer patients resulted in the appearance of only few, benign endometrial pathologies. The different endometrial pathologies were more common in patients who continued tamoxifen therapy, compared to patients who switched to aromatase inhibitors. (4) Endometrial cancer was recovered in significantly more patients who continued tamoxifen therapy as compared to those switched to aromatase inhibitors. However, some studies showed no significant statistical differences in the frequency of endometrial cancer diagnosed in the tamoxifen group as compared to the aromatase inhibitor group. These findings may hint on the possibility that aromatase inhibitors may provide a potential protective effect on the endometrium in patients previously treated with tamoxifen.


The effect of socioeconomic disadvantage for on-time graduation in an accelerated doctor of pharmacy program.
The purpose of this study was to determine if there is a relationship between socioeconomic disadvantage and student progression in an accelerated, three-year, doctor of pharmacy (PharmD) program. The percentage of socioeconomically disadvantaged students in Larkin University's applicant and accepted pool was compared to national data using an N-1 Chi-square. The on-time graduation rate for three classes of PharmD students were compared based on the economic or environmental disadvantage questions posed by Pharmacy College Application Service (PharmCAS). On-time graduation rates were also analyzed by sex, race/ethnicity, and geographical area using a Pearson's Chi-square. Student academic admissions profiles were compared by race/ethnicity using analysis of variance. Larkin University had a higher percentage of applicants and accepted candidates from certain underrepresented groups. There was no significant difference in on-time graduation for students who answered yes to any of the economic or environmental disadvantage questions as opposed to those who answered no, nor was there a significant difference in on-time graduation by sex or geographical area. For race, there was a significantly lower rate of on-time graduation for students who were Black or African American, even though their admissions criteria were comparable to that of students of other races. Students who had an economic or environmental disadvantage graduated on-time at the same rate as students who did not have such disadvantages. Black or African American students had lower on-time rates than other ethnic groups, but the reason for lower on-time graduation was unclear.


'I do what a woman should do': a grounded theory study of women's menstrual experiences at work in Mukono District, Uganda.
Menstrual health has received increasing recognition as an essential issue for public health and gender equality. A growing body of research has elucidated adolescent girls' menstrual needs and informed policy and practice responses. However, the experiences of adult women have received little attention, particularly in the workplace where many spend a significant proportion of their lives. To address this gap, we took a grounded theory approach to generate a nuanced understanding of working women's menstrual experiences, and the impact of menstruation on their work and health in Mukono District, Uganda. In-depth interviews were undertaken with 35 women aged 18-49. This included 21 women working in markets, 7 teachers and 7 healthcare facility workers. Frequent collaborative analysis sessions throughout data collection, coding of interview transcripts, and generation of participant, workplace, and category memos facilitated analysis. Our core category and underlying theory, 'being a responsible woman', underpinned women's experiences. 'Being responsible' meant keeping menstruation secret, and the body clean, at all times. These gendered expectations meant that any difficulty managing menses represented a failure of womanhood, met with disgust and shame. Difficulties with menstrual pain and heavy bleeding were excepted from these expectations and perceived as requiring compassion. Commercial menstrual products were expensive for most women, and many expressed concerns about the quality of cheaper brands. Workplace infrastructure, particularly unreliable water supply and cleanliness, was problematic for many women who resorted to travelling home or to other facilities to meet their needs. Menstruation presented a burden at work, causing some women to miss work and income, and many others to endure pain, discomfort and anxiety throughout their day. Our findings can inform norm and resource-focused responses to improve experiences and should provoke critical reflection on the discourse used in menstrual health advocacy in Uganda.


The influence of vibration type, frequency, body position and additional load on the neuromuscular activity during whole body vibration.
This study aimed to assess the influence of different whole body vibration (WBV) determinants on the electromyographic (EMG) activity during WBV in order to identify those training conditions that cause highest neuromuscular responses and therefore provide optimal training conditions. In a randomized cross-over study, the EMG activity of six leg muscles was analyzed in 18 subjects with respect to the following determinants: (1) vibration type (side-alternating vibration (SV) vs. synchronous vibration (SyV), (2) frequency (5-10-15-20-25-30 Hz), (3) knee flexion angle (10°-30°-60°), (4) stance condition (forefoot vs. normal stance) and (5) load variation (no extra load vs. additional load equal to one-third of the body weight). The results are: (1) neuromuscular activity during SV was enhanced compared to SyV (P < 0.05); (2) a progressive increase in frequency caused a progressive increase in EMG activity (P < 0.05); (3) the EMG activity was highest for the knee extensors when the knee joint was 60° flexed (P < 0.05); (4) for the plantar flexors in the forefoot stance condition (P < 0.05); and (5) additional load caused an increase in neuromuscular activation (P < 0.05). In conclusion, large variations of the EMG activation could be observed across conditions. However, with an appropriate adjustment of specific WBV determinants, high EMG activations and therefore high activation intensities could be achieved in the selected muscles. The combination of high vibration frequencies with additional load on an SV platform led to highest EMG activities. Regarding the body position, a knee flexion of 60° and forefoot stance appear to be beneficial for the knee extensors and the plantar flexors, respectively.


Towards the neurobiology of emotional body language.
People's faces show fear in many different circumstances. However, when people are terrified, as well as showing emotion, they run for cover. When we see a bodily expression of emotion, we immediately know what specific action is associated with a particular emotion, leaving little need for interpretation of the signal, as is the case for facial expressions. Research on emotional body language is rapidly emerging as a new field in cognitive and affective neuroscience. This article reviews how whole-body signals are automatically perceived and understood, and their role in emotional communication and decision-making.


Pharmacokinetics and hemodynamic effects of nisoldipine and its interaction with cimetidine.
Pharmacokinetics, diastolic blood pressure, and heart rate after oral and intravenous nisoldipine were studied in eight healthy subjects without and with cotreatment of cimetidine in a four-way crossover design. After intravenous infusion, elimination half-life (t1/2) was 4.0 +/- 2.3 hours, systemic clearance (CL) was 0.83 +/- 0.17 L/min, and volume of distribution was 1.6 +/- 0.6 L/kg. After oral nisoldipine, t1/2 was 3.8 +/- 1.3 hours and systemic availability was 3.9% +/- 3.5%. During cimetidine, t1/2 and CL were not different. Systemic availability increased to 5.7% +/- 2.8%. After all nisoldipine treatments a significant decrease in supine diastolic blood pressure (mean 10% to 16%) and increase in heart rate (mean 22% to 44%) were observed. Hemodynamic effects until 2 hours after nisoldipine administration could be fitted to a sigmoidal Emax model. At times after 2 hours a second effect peak was observed. Cimetidine inhibits the metabolism of nisoldipine but has no significant influence on hemodynamic parameters.


Airway Clearance of the Term Newborn.
The purpose of this study was to explore airway clearance practices for the preterm newborn in the neonatal intensive care unit (NICU). This descriptive, retrospective medical record review analyzed airway clearance practices in a level III regional NICU from 2016 to 2017 in preterm newborns ranging from 32 weeks to 36 weeks and 6 days. There were 87 preterm newborns and 384 suctioning events reviewed during the entire length of stay. Practices reviewed include device used, frequency, color, consistency, and tolerance of airway clearance. Method of nursing documentation for these practices was also reviewed. Babies born via cesarean required more suctioning (65.5%). Males (60.9%) required more airway clearance events than females (39.1%). After suction events, nurses reported no distress (74%), equal bilateral breath sounds (30%), desaturation (6%), and collectively color change, apnea, or bradycardia (<1%). The most common discharge diagnosis was respiratory distress syndrome (90%). Preterm newborns were suctioned with the blue bulb syringe (15.6%), oral/nasal-pharyngeal suction device (42.7%), and endotracheal suction devices (41.7%). Electronic medical records promote less detailed, narrative documentation and more point and click documentation. If electronic medical record systems are not designed to gather airway clearance indications, specifics about the procedure and the preterm newborn response to the procedure, evidence-based practice cannot be measured. More studies are needed to evaluate suction practices applied in the NICU setting.


Vital Capacity Impairment due to Neuromuscular Disease and its Correlation with Diaphragmatic Ultrasound: A Preliminary Study.
The purpose of this pilot study was to evaluate the correlation between diaphragmatic excursion measured by a right sub-costal ultrasound approach and forced vital capacity in patients with amyotrophic lateral sclerosis (ALS) or myotonic dystrophy (MD). All patients referred for pulmonary function testing underwent ultrasonic measurement of diaphragmatic excursion during quiet breathing, voluntary sniffing (Esniff) and forced breathing (EDEmax). Forty-five patients were included, mainly for amyotrophic lateral sclerosis or myotonic dystrophy. There was a significant correlation between EDEmax values and forced vital capacity (FVC) values (r = 0.68 [0.46–0.90], p < 0.0001) and between EDEmax values and percentage of predicted FVC values (r = 0.75 [0.55–0.95], p < 0.0001). At a threshold of EDEmax < 5.5 cm, the sensitivity and specificity of ultrasonic diaphragmatic excursion in predicting FVC ≤ 50% of theoretical values were 100% [66%–100%] and 69% [52%–84%] respectively, without any significant difference between males and females. There was no statistical correlation between maximal inspiratory pressure and Esniff.


Water and ion metabolism in placenta. I. water and ion content of rabbit placenta in different periods of gestation.
Total tissue water of rabbit plancenta decreases by 18% between the 9th day and the end of gestation. In the same period intracellular water decreases by 40% and the extracellular compartment swells. Total tissue sodium and chloride content increase by 34% and 27% respectively from the 16th to the 33rd day while potassium decreases by 30%. The intracellular concentration of these ions does not vary greatly during gestation. Moreover the total tissue magnesium content decreases by about 23% at the end of gestation while its intracellular concentration does not show marked changes. Calcium content of rabbit placenta substantially increases during gestation and intracellular calcium shows a fivefold increase from the 16th to the 33rd day of gestation. The results are discussed in terms of relation between water and ion content and placental tissue growth and aging.


A combination of serum leucine-rich α-2-glycoprotein 1, CA19-9 and interleukin-6 differentiate biliary tract cancer from benign biliary strictures.
Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy. Two-dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich α-2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers. We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase. These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC.


Therapy Monitoring with Functional and Molecular MR Imaging.
Cancer therapy is mainly based on different combinations of surgery, radiotherapy, and chemotherapy. Additionally, targeted therapies (designed to disrupt specific tumor hallmarks, such as angiogenesis, metabolism, proliferation, invasiveness, and immune evasion), hormonotherapy, immunotherapy, and interventional techniques have emerged as alternative oncologic treatments. Conventional imaging techniques and current response criteria do not always provide the necessary information regarding therapy success particularly to targeted therapies. In this setting, MR imaging offers an attractive combination of anatomic, physiologic, and molecular information, which may surpass these limitations, and is being increasingly used for therapy response assessment.


Heat sensitivity of sensory fibers in carpal tunnel syndrome.
Elevations in temperature may produce conduction block in demyelinated neurons. A well-described phenomenon in multiple sclerosis, it has also been reported in some patients with inflammatory demyelinating polyneuropathies. We used carpal tunnel syndrome (CTS) as a model to study the effect of heat on nerves with focal demyelination secondary to chronic compression. Compound motor and sensory responses were measured in 12 CTS patients and 12 normal subjects at 32 degrees C and with heating to 42 degrees C. Changes in relative motor response amplitude and area were similar for both normal subjects and CTS patients. In CTS patients, however, sensory response amplitude and area decreased 34.3% and 48.9%, significantly more than the 25.2% and 39.1% reductions in normal subjects (P=0.021 and P=0.018 respectively). We hypothesize that these reductions in response amplitude are secondary to the occurrence of heat-induced conduction block in demyelinated sensory neurons.


Teaching of the assessment of head and brain injury in UK dental schools--The Headway Survey.
Under the auspices of Headway--the brain injury association, the charity supplies information on head/brain injury and runs a telephone advice line: (0115 924 0800). Questionnaires regarding the undergraduate teaching related to head/brain injuries were sent to, and returned by, all 12 UK dental schools. The replies suggest that undergraduate teaching of this subject is patchy and inadequately prepares dentists to recognise and cope with patients who may have had head, and consequently brain, injuries. It is recommended that dental schools review their teaching of this subject and ensure that it is consistent with the current guidelines issued by the National Institute of Clinical Excellence (NICE) on the recognition of head injury and that the findings are brought to the attention of the General Dental Council in the context of the GDC's "The first five years" report.


Multi-detector row CT imaging of vertebral microstructure for evaluation of fracture risk.
We applied MDCT for in vivo evaluation of the microarchitecture of human vertebrae. Microstructure parameters, such as structure model index, Euler's number, and bone volume fraction, revealed higher relative risk for prevalent vertebral fracture than did BMD obtained by DXA. Thus, microstructure analysis by MDCT, together with simultaneously obtained volumetric BMD values, is useful for clinical assessment of fracture risk. BMD measurement by DXA alone has limitations in predicting fracture, and methods for clinical assessment of bone quality, such as microstructure, are awaited. This study was undertaken to examine the applicability of multidetector row CT (MDCT) for in vivo evaluation of trabecular microstructure. Optimal conditions for MDCT scanning were determined at a spatial resolution of 250 x 250 x 500 mum, using muCT data of excised human vertebra specimens as a reference. We analyzed the trabecular microstructure of the vertebrae of 82 postmenopausal women (55-76 years old), including 39 women with and 43 without a recent vertebral fracture. Microstructure indices obtained by MDCT scanning revealed higher relative risk for prevalent vertebral fracture (OR: 16.0 for structure model index, 13.6 for bone volume fraction, and 13.1 for Euler's number) than did spinal BMD obtained by DXA (OR: 4.8). MDCT could also provide volumetric BMD data, which had higher diagnostic value (OR: 12.7) than did DXA. Vertebral microarchitecture can be visualized by MDCT, and microstructure parameters obtained by MDCT, together with volumetric BMD, provided better diagnostic performance for assessing fracture risk than DXA measurement.


[Method of microroentgenography using a laser-plasma source of soft x-ray radiation in medicine and biology].
The paper analyses and illustrates experimentally the possibilities of using the method of microroentgenography for the analysis of the structure and element composition of thin sections of biological tissues. Soft roentgen radiation of laser plasma formed by focusing of a sufficiently powerful laser impulse on the surface of a solid-body target is used. The method requires no preliminary treatment of the specimens.


Persistent antegrade pulmonary blood flow post-glenn does not alter early post-Fontan outcomes in single-ventricle patients.
The bidirectional Glenn cavopulmonary anastomosis (BDG) represents the standard interim procedure in treatment of patients with single-ventricle physiology. Anterograde pulmonary blood flow (APBF) maintained after BDG has been shown both to improve and to complicate postoperative clinical course. We studied its effects on outcome after BDG and eventual Fontan completion. From November 1995 to November 2005, 60 patients underwent BDG and Fontan. All patients had APBF from the ventricle to the pulmonary artery at time of BDG. In group 1 (n = 39) APBF was maintained after BDG, whereas APBF was interrupted at BDG in group 2 (n = 21). Cardiac catheterization data, interstage morbidity, and postoperative outcome variables were recorded. Pre-BDG hemodynamics differed only in that the mean pulmonary artery pressure was higher in group 2 (17.0 +/- 4.4 mm Hg) than in group 1 (13.8 +/- 4.5 mm Hg; p = 0.03). There were no differences between groups 1 and 2 in BDG outcome variables. At pre-Fontan catheterization, group 1 had higher mean pulmonary artery pressure (13.3 versus 10.9 mm Hg, p = 0.01), arterial oxygen saturation (85.8 versus 80.9%, p = 0.0001), and fewer collateral vessels were coil embolized than in group 2 (0.9 versus 1.6, p = 0.02). Mean ventricular end-diastolic pressure was similar between groups. The Nakata index in group 1 remained stable from pre-BDG to pre-Fontan (348 versus 391, p = 0.24), but it decreased in group 2 (375 versus 227, p = 0.046). Patients with anterograde pulmonary blood flow after BDG had a modest increase in pulmonary artery growth and arterial oxygen saturations, and decreased collateral vessel formation. This did not, however, confer additional benefit on outcome after BDG or on eventual Fontan completion.


Simultaneous kinetic-spectrophotometric determination of carbidopa, levodopa and methyldopa in the presence of citrate with the aid of multivariate calibration and artificial neural networks.
The kinetic methodology based on the difference of reaction rates, is based on the reaction between a common oxidizing agents such as tris(1,10-phenanthroline) and iron(III) complex (ferriin, [Fe (phen)3]3+) in the presence of citrate and spectrophotometrically, monitoring the changes of absorbance at the maximum wavelength of 511 nm. Experimental conditions such as pH, reagents and citrate concentrations were optimized, and the data obtained from the experiments were processed by several chemometric approaches, such as artificial neural network (ANN) and partial least squares (PLS). A set of synthetic mixtures of carbidopa (CD), levodopa (LD) and methyldopa (MD) was evaluated and the results obtained by the applications of these chemometric approaches were discussed and compared. It was found that the back propagation artificial neural network (BP-ANN) method afforded better precision relatively than those of radial basis function artificial neural networks (RBF-ANN) and PLS. The proposed method was also applied satisfactorily to the determination of carbidopa, levodopa and methyldopa in real samples.


Aflatoxin M1 Concentration in Various Dairy Products: Evidence for Biologically Reduced Amount of AFM1 in Yoghurt.
Aflatoxin M1 (AFM1), a carcinogenic substance is found in milk and dairy products. The effect of season and type of dairy products on AFMi level in northern Iran was investigated in this study. Three hundred samples (each season 75 samples) including raw and pasteurized milk, yoghurt, cheese, and cream samples were collected from three distinct milk producing farms. The samples were subjected to chemical and solid phase extractions and were analyzed by using HPLC technique. Recovery percentages, limit of detection and limit of quantification values were determined. Seventy percent and 98% were the minimum and maximum recoveries for cheese and raw milk, respectively and 0.021 and 0.063 ppb were the limit of detection and limit of quantification values for AFM1. We found that in autumn and winter the highest level (0.121 ppb) of AFM1 in cheese and cream samples and failed to detect any AFM1 in spring samples. Interestingly, our data showed that the yoghurt samples had the lowest level of AFM1 in all seasons. There are significant differences between the AFM1 levels in dairy products in various seasons and also various types of products, suggesting spring and summer yoghurt samples as the safest products from AFM1 level point of view.


Neuroprotective Effects of Anti-diabetic Drugs in the Treatment of Patients with Diabetes and Glaucoma or at High Risk for Glaucoma.
There is an association between glaucoma and several risk factors and metabolic diseases, such as type 2 diabetes mellitus. Diabetes mellitus leads to neurodegenerative changes, both peripherally and in the brain. This might be a shared pathophysiology and etiology for both glaucoma and diabetes. It is interesting that drugs for the treatment of diabetes seem to have neuroprotective properties independent of their blood sugar reduction. Although prospective, randomized, clinical studies are still missing, particularly metformin and glucagon-like peptide receptor agonists (GLP 1 RA) seem to have neuroprotective effects. Sulphonylureas (e.g., glibenclamide, glimepiride) are still used. They frequently potently reduce blood pressure but may be less neuroprotective. In the present review, the evidence for neuroprotective effects of the different antidiabetic drugs is presented and a possible differential therapy for patients with diabetes and glaucoma, or at high risk of glaucoma, will be discussed.


WITHDRAWN: Use of Repositionable Transcatheter Aortic Valve Systems in Past Mechanical Prosthetic Mitral Valve Recipients.
This article has been withdrawn, at the request of the Editor, due to the absence of the corresponding permissions for use of all the data/images. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Efficacy and safety of electroacupuncture for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: a single-blinded, randomized, sham-controlled trial.
Oxaliplatin-based chemotherapy is a major first-line conventional therapy for advanced and metastatic colorectal cancer (CRC). However, oxaliplatin causes chemotherapy-induced peripheral neuropathy (CIPN). Acupuncture has long been used to alleviate limb numbness in Chinese medicine practice. The aim of this study was to examine the efficacy and safety of electroacupuncture (EA) for the alleviation of CIPN in CRC patients. This was a pilot single-blinded, randomized, sham-controlled trial. Sixty eligible patients, who had been diagnosed with CRC and were undergoing oxaliplatin-based chemotherapy, were randomized in a ratio of 1:1 to the EA intervention group or sham acupuncture (SA) control group. During a 12-week treatment period, patients in the EA group received EA once a week, while patients in the SA group received SA; both groups were followed up for 12 weeks. Compared with the SA group, the EA group exhibited significant alleviation of CIPN severity during chemotherapy. Moreover, EA also improved the physical function, role function, and social function of CRC patients. However, there were no significant differences in tests of vibration or light touch sensation. In addition, EA appeared to be a safe treatment for CIPN and was both feasible and acceptable to CRC patients during chemotherapy. This study showed preliminary evidence for the efficacy and safety of EA in acute CIPN among CRC patients, although further studies are needed to verify these effects and to further explore the potential role of EA in chronic CIPN (effects on which remain unclear). NCT03582423 (ClinicalTrials.gov).


A new, simple and rapid method for enumerating human T lymphocytes in full blood: the E. coli (ATCC 11303) rosette test.
A new bacterial rosette technique for enumerating T lymphocytes is described. E. coli (strain B; ATCC 11303), fixed in formaldehyde after overnight growth in thioglycolate medium, are mixed with washed whole blood cells (100 microliters) and after incubation at 4 degrees C, slides are made, stained and counted. The nature of the lymphocytes forming E. coli rosettes was demonstrated by comparing their cytochemical staining characteristics with those of E rosetted lymphocytes, and by mixed E. coli and E, mouse E rosette and Fc receptor tests, and by mixed E. coli rosette tests and anti-Ig staining. E. coli and E rosette tests in controls and pediatric patients were also compared. The results show that T mu and T gamma cells rosette with E. coli.