Emergence of new-onset psychotic disorder following recovery from LGI1 antibody-associated limbic encephalitis.
Neuronal autoantibodies targeting cell surface antigens have been described in association with autoimmune encephalitides which frequently feature psychosis and other psychiatric disturbances alongside neurological signs and symptoms. Little has been written however about the long-term psychiatric status of individuals following recovery from the acute phase of autoimmune encephalitis, despite case series and anecdotal evidence suggesting this may be a cause of considerable disability. Here, we describe a man aged 58 years with no psychiatric history who developed a severe and acute psychotic disorder following resolution of a protracted course of limbic encephalitis associated with antibodies to leucine-rich glioma inactivated 1 protein. No indications of a gross ongoing inflammatory or encephalopathic process were present at presentation of his psychosis. Possible aetiologies of his acute psychosis are discussed. This case highlights the importance of ongoing psychiatric follow-up of patients following an episode of autoimmune encephalitis.


[Otorhinolaryngologic symptoms caused by the intranasal abuse of cocaine. Report of a case].
Cocaine abuse is associated with medical complications that depends on the route of administration. Intranasal "snorting" is associated with complications secondary to chronic irritation on the nasal mucosa. A case of long-standing intranasal cocaine abuse is presented with unusual complications: septal and palatal necrosis, osteolytic sinusitis and bilateral optic neuropathy. The CT scan demonstrated a soft-tissue mass in etmoid and sphenoidal sinus and orbits. The histopathologic examination revealed a nonspecific pattern of chronic inflammation with no evidence suggestive of infection, neoplasm or lethal midline granuloma. The case had a fatal outcome. Because of the constellation of singular manifestations we discuss the differential diagnosis. Interdisciplinary approach is stressed. Emphasis is made in early diagnosis.


MOMO syndrome associated with autism: a case report.
This is a case report of macrosomia, obesity, macrocephaly and ocular abnormalities (MOMO syndrome) associated with autism. Studies on genetic or environmental syndromes associated with autism can provide genetic markers or uncover relevant events, and are very important for the definition of autism subgroups in future molecular research.


Lifespan differences in emotional contagion while watching emotion-eliciting videos.
Previous research has examined empathic concern by presenting toddlers with a sad stimulus and examining their emotional response, with the conclusion that toddlers display empathy. Yet, such research has failed to include basic control conditions involving some other aversive stimulus such as white noise. Nor has it compared toddlers to adults to examine potential development in empathy. In the present study, we showed toddlers and adults four video types: infant crying, infant laughing, infant babbling, and a neutral infant accompanied by white noise. We then coded happiness and sadness while viewing the videos, and created a difference score (happiness minus sadness), testing 52 toddlers and 61 adults. Whereas adults showed more sadness towards infant crying than any other stimulus, toddlers' response to crying and white noise was similar. Thus, the toddler response to crying was comparable to previous studies (slight sadness), but was no different to white noise and was significantly reduced relative to adults. As such, toddlers' response seemed to be better characterized as a reaction to an aversive stimulus rather than empathy.


[Molecular markers and its clone for salt tolerance gene in wheat].
Genetic and RAPD analysis were studied among [4] individuals in F2 segregated population originating from a cross between wheat cultivator Nongda 85021 (female parent, salt sensitive) and Chadian Red (male parent, salt tolerant). For genetic analysis and chi-square test gave a good fit of 1:2:1 ratio showing that one major gene was controlling the salt tolerant character in Chadian Red. DNA of F2 population was extracted to develop tolerant and sensitive gene pools, respectively, based the BSA (Bulked Segregate Analysis). By RAPD (Randomly Amplified Polymorphic DNAs), 520 random primers were used to amplify the two types of gene pools. Only primer OPZ09 was found to be polymorphic with a fragment of 590 bp in the two parents, F1 and F2 populations. So, the specific fragment OPZ09-590 was, a RAPD marker linked to salt tolerance gene in Chadian Red. By the software JOINMAP (Version 1.4), the recombination was 5.674% and the linking distance was 6.557 cM. OPZ09-590 was extracted from the agarose and mixed with pUCm-T vector, then the vector was transferred into JM109. The clone was determined 591 bp after being sequenced. It indicated that the RAPD marker of salt tolerance gene in Chadian Red was OPZ09-591.


Porcine 2', 5'-oligoadenylate synthetases inhibit Japanese encephalitis virus replication in vitro.
The 2', 5'-oligoadenylate synthetases (OAS) are antiviral proteins and several isoforms have been identified as flavivirus-resistance biomarkers in human and mouse. The expression kinetics and antiviral functions of porcine OAS family (OAS1, OAS2, and OASL) in PK-15 cells following infection by Japanese encephalitis virus (JEV) were evaluated in the present study. The endogenous expression of the three OAS genes was efficiently induced by IFN-α treatment in PK-15 cells. However, expression of pOAS1 and pOAS2 responded more quickly than pOASL. Infection by JEV also induced the expression of the pOAS isoforms, but at a significantly lower level than that observed following IFN-α stimulation. Transient overexpression of pOASL and pOAS1 inhibited JEV replication more efficiently than OAS2 overexpression. Interestingly, knockdown of pOAS2 expression by siRNA treatment led to the highest increase in JEV multiplication. Co-silencing of RNase L and each pOAS revealed that the anti-JEV function of pOAS1 and pOAS2 were RNase L dependent, while the antiviral activity of pOASL was not. In conclusion, all pOAS isoforms play a significant role in the response to JEV infection, and are differentially induced by different stimuli. The alternative pathways of antiviral activity stimulated by OASL require further study.


Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury.
Adult liver stem cells are usually maintained in a quiescent/slow-cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. We studied LGR5-positive stem cells using diphtheria toxin receptor and green fluorescent protein (GFP) knock-in mice. In these mice, LGR5-positive cells specifically coexpress diphtheria toxin receptor and the GFP reporter. Lineage-tracing experiments were performed in mice in which LGR5-positive stem cells and their daughter cells expressed a yellow fluorescent protein/mTmG reporter. Slow-cycling stem cells were investigated using GFP-based, Tet-on controlled transgenic mice. We studied the dynamics of both stem cell populations during liver homeostasis and injury induced by carbon tetrachloride. Stem cells were isolated from mouse liver and organoid formation assays were performed. We analyzed hepatocyte and cholangiocyte lineage differentiation in cultured organoids. We did not detect LGR5-expressing stem cells in livers of mice at any stage of a lifespan, but only following liver injury induced by carbon tetrachloride. In the liver stem cell niche, where the proliferating LGR5+ cells are located, we identified a quiescent/slow-cycling cell population, called label-retaining cells (LRCs). These cells were present in the homeostatic liver, capable of retaining the GFP label over 1 year, and expressed a panel of progenitor/stem cell markers. Isolated single LRCs were capable of forming organoids that could be carried in culture, expanded for months, and differentiated into hepatocyte and cholangiocyte lineages in vitro, demonstrating their bona fide stem cell properties. More interestingly, LRCs responded to liver injury and gave rise to LGR5-expressing stem cells, as well as other potential progenitor/stem cell populations, including SOX9- and CD44-positive cells. Proliferative LGR5 cells are an intermediate stem cell population in the liver that emerge only during tissue injury. In contrast, LRCs are quiescent stem cells that are present in homeostatic liver, respond to tissue injury, and can give rise to LGR5 stem cells, as well as SOX9- and CD44-positive cells.


[Bronchial mucoepidermoid carcinoma in childhood. Case report].
Bronchial tumors are rare in children. Most of them are malignant, being the carcinoid tumor the most common. Less frequently the mucoepidermoid carcinoma is found in the tracheobronchial tree. Mucoepidermoid carcinoma accounts for 0.1 to 0.2% of all malignant bronchopulmonary tumors. It manifests with symptoms of airway obstruction and/or recurrent pneumonias. Early diagnosis and appropriate treatment are of great importance in the prognosis. Bronchoscopy with biopsy of the endobronchial mass is the method of choice to confirm the diagnosis. Treatment consists of surgical resection of the lesion. We present an 11-year-old girl with dyspnea on exertion and cough due to a low malignant mucoepidermoid arcinoma of the ronchi. We describe the clinical manifestations, the diagnostic methods and the treatment of this rare neoplasia in pediatrics.


Molecular characterization and functional analysis of the hepcidin gene from roughskin sculpin (Trachidermus fasciatus).
Hepcidin is a kind of cysteine-rich antimicrobial peptide that plays a vital role in host innate immune activity and iron regulation. Here, we report the molecular characterization and functional analysis of a novel hamp1 hepcidin isoforms Tf-Hep from roughskin sculpin, Trachidermus fasciatus. A cDNA fragment of 988 bp with an ORF of 273 bp was obtained. The coding sequence encodes for a signal peptide of 24 amino acids coupled with a prodomain of 40 amino acids and a mature peptide of 26 amino acids. Tissue distribution analysis indicated that Tf-Hep was most abundant in the liver. It could be significantly induced post lipopolysaccharide (LPS) challenge and heavy metal exposure. The mature peptide was expressed as a 6.061 kDa fusion protein in Pichia pastoris GS115. The active purified recombinant protein (rTf-Hep) exhibited a wide spectrum of potent antimicrobial activity in vitro against 4 Gram-negative bacteria Escherichia coli, Vibrio Anguillarum, Klebsiella pneumoniae, and Pseudomonas aeruginosa and 4 Gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, Bacillus thuringiensis, and Bacillus megaterium with minimum inhibitory concentrations (MICs) of 5-80 μg/ml (0.825-13.2 μM). It also displayed high affinity to polysaccharides on bacteria surface including LPS, lipoteichoic acid (LTA) and peptidoglycan (PGN). We further revealed that rTf-hep was capable of agglutinating 6 of the 8 bacteria. All these results suggest that rTf-hep may be both an antibacterial effector and a pattern recognition molecule in fish immune defense. The in vivo bacterial treatment results demonstrated that rTf-Hep could significantly improve the survival rate of fish infected with V. anguillarum. Taken together, these data indicate an important role for Tf-hep in the innate immunity of Trachidermus fasciatus and suggest its potential application in aquaculture for increasing fish resistance to disease.


Dopaminergic modulation of reward-guided decision making in alcohol-preferring AA rats.
R**esults from animal gambling models have highlighted the importance of dopaminergic neurotransmission in modulating decision making when large sucrose rewards are combined with uncertainty. The majority of these models use food restriction as a tool to motivate animals to accomplish operant behavioral tasks, in which sucrose is used as a reward. As enhanced motivation to obtain sucrose due to hunger may impact its reward-seeking effect, we wanted to examine the decision-making behavior of rats in a situation where rats were fed ad libitum. For this purpose, we chose alcohol-preferring AA (alko alcohol) rats, as these rats have been shown to have high preference for sweet agents. In the present study, AA rats were trained to self-administer sucrose pellet rewards in a two-lever choice task (one pellet vs. three pellets). Once rational choice behavior had been established, the probability of gaining three pellets was decreased over time (50%, 33%, 25% then 20%). The effect of d-amphetamine on decision making was studied at every probability level, as well as the effect of the dopamine D1 receptor agonist SKF-81297 and D2 agonist quinpirole at probability levels of 100% and 25%. d-Amphetamine increased unprofitable choices in a dose-dependent manner at the two lowest probability levels. Quinpirole increased the frequency of unprofitable decisions at the 25% probability level, and SKF-82197 did not affect choice behavior. These results mirror the findings of probabilistic discounting studies using food-restricted rats. Based on this, the use of AA rats provides a new approach for studies on reward-guided decision making.


Jaw kinematics and tongue protraction-retraction during chewing and drinking in the pig.
Mastication and drinking are rhythmic and cyclic oral behaviors that require interactions between the tongue, jaw and a food or liquid bolus, respectively. During mastication, the tongue transports and positions the bolus for breakdown between the teeth. During drinking, the tongue aids in ingestion and then transports the bolus to the oropharynx. The objective of this study was to compare jaw and tongue kinematics during chewing and drinking in pigs. We hypothesized there would be differences in jaw gape cycle dynamics and tongue protraction-retraction between behaviors. Mastication cycles had an extended slow-close phase, reflecting tooth-food-tooth contact, whereas drinking cycles had an extended slow-open phase, corresponding to tongue protrusion into the liquid. Compared with chewing, drinking jaw movements were of lower magnitude for all degrees of freedom examined (jaw protraction, yaw and pitch), and were bilaterally symmetrical with virtually no yaw. The magnitude of tongue protraction-retraction (Txt), relative to a mandibular coordinate system, was greater during mastication than during drinking, but there were minimal differences in the timing of maximum and minimum Txt relative to the jaw gape cycle between behaviors. However, during drinking, the tongue tip is often located outside the oral cavity for the entire cycle, leading to differences between behaviors in the timing of anterior marker maximum Txt. This demonstrates that there is variation in tongue-jaw coordination between behaviors. These results show that jaw and tongue movements vary significantly between mastication and drinking, which hints at differences in the central control of these behaviors.


New and known phenylpropanoid glycosides from mountain cultivated ginseng.
Two new phenylpropanoid glycosides elucidated as 2,6-dimethoxyphenyl-4-propylene-1-O-β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside (1) and 2-methoxyphenyl-4-propylene-1-O-β-D-apiofuranosyl-(1-6)-β-D-glucopyranoside (2), along with three known phenylpropanoid glycosides (3-5) were isolated from Mountain Cultivated Ginseng. The structures of compounds 1-5 were elucidated on the basis of comprehensive spectroscopic data including 1D, 2D NMR spectra, and MS. In addition, in vitro cytotoxicity of all the isolated compounds was evaluated against HELA cell.


The papaverine test for blood flow potential of ileo-femoral arteries.
To establish drug and an optimal dose for a pharmacological test of the blood flow potential of an artery, the effect of intra-arterial injection of papaverine in varying doses was observed. The response to papaverine was then compared with that of other vasodilating drugs and with the physiological vasodilation of sympathectomy, exercise and postischemic hyperemia. In reconstructed atheromatous arteries, the injection of 40 mg papaverine HCl was found to induce a maximal local flow response, increasing blood flow in artery by approximately 250%. In normal arteries the response was higher. Tolazoline and isoxuprine induced a lower blood flow response and a higher fall in systemic blood pressure. The flow induced by papaverine was higher than flow after sympathectomy and light exercise and amounted to 88% of the maximum seen after 5 minutes ischemia. It is concluded that the blood flow induced by intra-arterial injection of 40 mg papaverine HCl represents a useful reference for flow potential of this artery.


Comparative bioavailability of two furosemide formulations in humans.
Twelve healthy male volunteers participated in a balanced crossover comparison of a brand-name and generic furosemide formulations. Each treatment was given as a single 40-mg tablet following an overnight fast. Furosemide concentrations in plasma and urine were determined up to 24 h after treatment; urine output and urinary sodium excretion were also measured. In comparison with the brand-name tablets, generic furosemide was significantly less bioavailable. Using a 95% confidence interval approach, generic furosemide gave up to 66% lower maximum furosemide plasma levels, up to 52% less area under the plasma level curve to infinite time, and up to 37% less urinary recovery of furosemide. Comparison of the effect of the two treatments was a less sensitive measurement of bioequivalence. Confidence intervals for differences in urinary output and sodium excretion over the period of maximum effect (0-4 h) were, however, asymmetrical, and pharmacodynamic differences between treatments were significant at the 10% level.


[Analysis of the products of ergosta-7,22-dien-3-beta-ol biotransformation by a Nocardia erythropolis culture].
The products of biotransformation by Nocardia erythropolis-402 of the microbial sterol ergosta-7,22-dien-3 beta-ol isolated from a Saccharomyces cerevisiae mutant were studied. The products were identified as ergosta-7,22-dien-3-one and ergosta-7,22-dien-17 alpha-ol-3-one by thin-layer chromatography, UV-spectrophotometry and mass-spectroscopy. It was found that the existence of 7-8 double bond slowed down the cleavage of the sterol side chain. The absence of 5-6 double bond prevents the formation of delta 4-3-ketosystem of coupled bonds.


Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response.
The skin is an important immunological organ with an outer protective layer, the stratum corneum forming a barrier between the skin-associated lymphoid tissue and the environment. We show that gently removing the stratum corneum with adhesive tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion by T cells from draining lymph nodes and high levels of specific IgE and IgG1 with no IgG2a showed that the immune responses induced following epicutaneous antigen exposure are strongly Th2 biased. Similar responses were obtained with different antigens and mouse strains. In contrast, subcutaneous immunization with antigen delivery into the dermis was less potent and gave predominantly Th1 responses. Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate. Rapid migration from epidermis to draining lymph node was obtained, however, by exposure to antigen after removal of the stratum corneum, suggesting that maturation and migration of Langerhans cells are independently regulated events. These results suggest that antigen presentation by Langerhans cells gives predominantly Th2 responses. This may provide an explanation for allergic sensitization to some antigens. It may also be a useful non-invasive, non-adjuvant-dependent method of vaccination.


Effect of epidural morphine on the Hoffman-reflex in man.
Four healthy, young subjects undergoing knee surgery with epidural anaesthesia were given epidural morphine for the relief of post-surgical pain. The Hoffman (H)-reflex was tested before and after the injection of morphine in the epidural space. The reflex was chosen as a monitor of the function of monosynaptic pathways in the spinal cord. Analogue scales for the measurement of pain revealed a satisfactory decrease of nociception after morphine injection, while the H-reflex was not significantly affected. This study may confirm that monosynaptic reflexes are not affected by epidural administration of morphine and that they are probably not involved in pain transmission.


Analysis of the embryonic phenotype of Bent tail, a mouse model for X-linked neural tube defects.
Neural tube defects, mostly believed to result from closure defects of the neural tube during embryonic development, are frequently observed congenital malformations in humans. Since the etiology of these defects is not well understood yet, many animal models for neural tube defects, either arising from spontaneous mutations or generated by gene targeting, are being studied. The Bent tail mouse is a model for X-linked neural tube defects. This mutant has a characteristic short and kinked tail. Exencephaly occurs in Bent tail embryos with a frequency of 11-16%. Laterality defects also belong to the phenotypic spectrum. In this study, we analyzed the embryonic phenotype in further detail using scanning electron microscopy during the stages of neurulation. We observed a number of defects in both wild type and Bent tail embryos, including a kinked neural tube, tight amnion, delay in axial rotation and even malrotation. The severity or frequency of most defects, the delay in axial rotation excluded, was significantly higher in Bent tail embryos compared to wild type embryos. Other abnormalities were seen in Bent tail embryos only. These defects were related to anterior and posterior neural tube closure and resulted in exencephaly and a closure delay of the posterior neuropore, respectively. The exencephalic phenotype was further analyzed by light microscopy in ED14 embryos, showing disorganization and overgrowth in the mesencephalon and rhombencephalon. In conclusion, the anterior and posterior neural tube closure defects in the Bent tail are strictly linked to the genetic defect in this mouse. Other phenotypic features described in this study also occur in the wild type genetic background of the Bent tail strain. Apparently, the genetic background contains elements conducive to these developmental abnormalities.


Investigation of the Relationship Between BPPV with Anxiety, Sleep Quality and Falls.
To investigate the effects of dizziness on sleep quality and psychological status in patients with benign paroxysmal positional vertigo (BPPV) and to evaluate its relationship with falls. A Demographic Data Form, a Visual Vertigo Analog Scale, the Falls Efficacy Scale - International (FES-I), the Hospital Anxiety and Depression Scale (HADS), and the Pittsburgh Sleep Quality Index (PSQI) were administered in 102 individuals diagnosed with BPPV by videonystagmography test. The same scales were applied to 75 healthy volunteers as the control group, and the two groups were compared. The BPPV group was divided into two groups as posterior canal and lateral canal BPPV. These two groups were compared among themselves and with the control group. A statistically significant difference was found between the BPPV and control groups, the lateral canal BPPV and posterior canal BPPV groups, the lateral canal BPPV and control groups, and the posterior canal BPPV and control groups in terms of total scores of the PSQI, the FES-I, and the HADS (p<0.001). In the regression model, the FES-I score was fully explained by the PSQI and HADS scores (p<0.001). BPPV significantly affects sleep quality, psychological state, and the risk of fall. The negative effects of BPPV restrict daily living activities, affect the prognosis of the disease, and increase the risk of falling. Considering that psychiatric issues and sleep problems increase the risk of falling in individuals with BPPV, counseling services on this issue would reduce the incidence of falls and related injuries.


[An experimental animal model for inducing fetal distress during pregnancy].
In order to try to understand and treat efficiently pathology in the human pregnant woman the authors have carried out experimental work on animals. Twenty four pregnant ewes with a single fetus were operated on in the last trimester of pregnancy. Fetal distress was provoked by injecting microspheres into the aorta beneath the renal arteries via the femoral route. The first results in terms of survival, by chemical and Doppler measurements were very encouraging. The operation itself was not a significantly disturbing factor, but the injection of microspheres did cause fetal distress. This experiment should be continued.


Formation and isolation of an iron-tripyrrole complex from heme degradation.
Addition of dioxygen to a solution of (py)2Fe(OEPO) (1) (where OEPO is the trianion of octaethyloxophlorin) in pyridine-d5 at 23 degrees C results in a series of oxidative changes that have been followed by 1H NMR spectroscopy. After 4 h, the resonances of 1 have vanished, while several sets of new resonances have developed. The most intense of these are identified as belonging to (py)2FeIII(OEB) (2) by comparison with the previously obtained spectrum of this species, which contains a ring-opened tetrapyrrole. After the sample was left standing for 1 day, further changes occur which produce a sample that is stable, because 1H NMR spectroscopic examination reveals no further changes on continued exposure to dioxygen or air. The product, (py)2FeIII(HETP) (3), where HETP is the dianion of a hexaethyltripyrrole, has been converted into (n-Bu4N)[ClFeIII(HETP)] by treatment with tetra(n-butyl)ammonium chloride. Red (n-Bu4N)[ClFeIII(HETP)] has been isolated and characterized by single-crystal X-ray diffraction.


Gastric MALT-lymphoma and Helicobacter pylori infection.
The presence of lymphoid tissue in the gastric mucosa is virtually pathognomonic of Helicobacter pylori infection. This lymphoid tissue has mucosa-associated lymphoid tissue (MALT) characteristics suggesting that H. pylori infection may represent a stimulus for the growth of gastric MALT lymphoma. H. pylori can be detected in more than 90% of patients with low-grade gastric MALT lymphoma supporting the aetiological role of the organism. The strongest evidence for the significance of H. pylori in the pathogenesis of low aetological-grade gastric MALT lymphoma is provided by clinical studies showing that cure of H. pylori infection is followed by a complete regression of these tumours in most patients. This paper reviews the current knowledge about antibacterial treatment of low-grade gastric MALT lymphoma, and immunological and molecular aspects in the pathogenesis of the disease.


Clinical Applications of Esophageal Multichannel Intraluminal Impedance Testing.
Multichannel intraluminal impedance is a relatively new technology that allows detection of bolus movement in the gastrointestinal tract without the use of radiation. In clinical applications it is combined with manometry, allowing a better evaluation of the functional characteristics (ie, bolus transit) of esophageal motility abnormalities. When combined with pH monitoring, it provides more comprehensive data on both acid and nonacid gastroesophageal reflux.


COVID-19: A case for the collection of race data in Canada and abroad.
Racialized populations have consistently been shown to have poorer health outcomes worldwide. This pattern has become even more prominent in the wake of the coronavirus disease 2019 (COVID-19) pandemic. In countries where race disaggregated data are routinely collected, such as the United States and the United Kingdom, preliminary reports have identified that racialized populations are at a heightened risk of COVID-19 infection and mortality. Similar patterns are emerging in Canada but rely on proxy measures such as neighbourhood diversity to account for race, in the absence of person-level data. It follows that the collection of race disaggregated data in Canada is a crucial element in identifying individuals at risk of poorer COVID-19 outcomes and developing targeted public health interventions to mitigate risk among Canada's racialized populations. Given this continuing gap, advocating for timely access to this data is of great importance owing to the challenges that the COVID-19 pandemic has highlighted amongst racialized populations in Canada and worldwide.


Evaluation of Lure Combinations Containing Essential Oils and Volatile Spiroketals for Detection of Host-Seeking Xyleborus glabratus (Coleoptera: Curculionidae: Scolytinae).
The invasive redbay ambrosia beetle, Xyleborus glabratus Eichhoff (Coleoptera: Curculionidae: Scolytinae), vectors the fungal pathogen (Raffaelea lauricola) that causes laurel wilt, a disease responsible for widespread mortality of trees in the Lauraceae in the southeastern United States. Early detection of incipient vector populations may allow for management practices that could successfully mitigate damage. Developing new, highly effective attractants is a priority for improving sensitivity of early detection efforts. In this study, two field tests were conducted to evaluate combinations of commercially available bark and ambrosia beetle lures for enhanced attraction of host-seeking female X. glabratus. In addition, lures were compared for capture of nontarget scolytine beetles. In the first experiment, traps baited with a combination of cubeb oil, conophthorin, chalcogran, and ethanol captured greater numbers of X. glabratus than cubeb oil alone, the current standard attractant. However, this combination lure resulted in higher nontarget scolytine captures than with the cubeb lure. In the second field test, an oil enriched in the sesquiterpene α-copaene caught significantly more X. glabratus than other lures currently available for monitoring this pest. There were no differences in efficacy between cubeb oil lures produced by two different manufacturers, and a combination lure containing copaiba and cubeb oils did not increase captures over the cubeb lure alone. Results of these two tests suggest that increased sensitivity for detection of X. glabratus may be achieved with a multicomponent lure that incorporates α-copaene, spiroketals, and low release of ethanol.


Do HIV prevention interventions in Asia lead to increase in condom utilization?: A meta-analysis study.
This meta-analytic review synthesizes the findings of published independent studies that assessed the effectiveness of HIV prevention interventions in promoting condom usage in Asia. We focused on 20 studies that used randomized control studies to establish whether HIV prevention interventions lead to increased condom utilization. As compared with the average control group client, we found that 68% of the clients who participated in an intervention group increased their condom usage. The effectiveness of HIV prevention intervention is not related to country and rural-urban contexts, to male-female samples, to the type of outcome measured, or the timing of the latest follow-up assessment. The implications of these findings are that policy-makers, health administrators, and international donors should view behavioral HIV prevention interventions as an effective approach through which to increase condom usage in order to reduce the HIV infection rate in Asia.


[Study for distribution level of disinfection byproducts in drinking water from six cities in China].
To find the distribution level and geographical variations of disinfection by-products (DBPs) in drinking water. The samples were selected from water utilities in six cities (Daqing, Beijing, Tianjin, Zhengzhou, Changsha and Shenzhen) of China. The water source and technology of water treatment were investigated and the indices including trihalomethanes (THMs) and haloacetic acids (HAAs) in main DBPs and natural organic materials (NOM), pH, chlorine dosage and temperature were determined. In six cities the highest concentrations of TTHMs and THAAs in the distribution system were 92.8 microg/L and 40.0 microg/L, respectively. The concentration of every compound of THMs and HAAs was under the limit of standards for drinking water quality, but the concentrations of 'TTHMs at some samples were higher than the maximum acceptable level (MAC) defined by standards for drinking water quality. The geographical variations of THMs and HAAs in six cities were Zhengzhou > Tianjin > Daqing > Beijing > Shenzhen > Changsha and Changsha > Tianjin > Shenzhen > Daqing > Zhengzhou > Beijing, respectively. The levels of THMs of drinking water at Tianjin and Zhengzhou were higher than the others and the levels of HAAs of drinking water at Changsha, Tianjin and Shenzhen were higher than the others. The seasonal variations of both groups of THMs and HAAs were high in summer and low in winter. The pollution level of DBPs in drinking water from Chinese six cities were low. The concentration of DBPs related to seasonal. THMs distributed mainly to the North and HAAs distributed mainly to the South.


Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: a role in Alzheimer's disease?
Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (Abeta) that is derived from amyloid-beta protein precursor (AbetaPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and AbetaPP and Abeta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at > or = 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in AbetaPP and Abeta1-40 peptide levels were detected in conditioned media samples.


Chlorhexidine-releasing implant coating on intramedullary nail reduces infection in a rat model.
The use of internal intramedullary nails for long bone fracture fixation is a common practice among surgeons. Bacteria naturally attach to these devices, increasing the risk for wound infection, which can result in non- or malunion, additional surgical procedures and extended hospital stays. Intramedullary nail surface properties can be modified to reduce bacterial colonisation and potentially infectious complications. In the current study, a coating combining a non-fouling property with leaching chlorhexidine for orthopaedic implantation was tested. Coating stability and chlorhexidine release were evaluated in vitro. Using a rat model of intramedullary fixation and infection, the effect of the coating on microbial colonisation and fracture healing was evaluated in vivo by quantitative microbiology, micro-computed tomography, plain radiography, three-point bending and/or histology. Low dose systemic cefazolin was administered to increase the similarities to clinical practice, without overshadowing the effect of the anti-infective coating. When introduced into a contaminated wound, the non-fouling chlorhexidine-coated implant reduced the overall bacteria colonisation within the bone and on the implant, reduced the osteolysis and increased the radiographic union, confirming its potential for reducing complications in wounds at high risk of infection. However, when implanted into a sterile wound, non-union increased. Further studies are required to best optimise the anti-microbial effectiveness, while not sacrificing fracture union.


Current status of cardiac surgery allied health professionals in Asia.
More and more allied health professions are getting involved in clinical health care. One estimate reported allied health personnel makes up 60 percent of the total health workforce. In Asia, in the field of cardiothoracic surgery, allied health personnel includes perfusionists, physician assistants, physiotherapist, intensivists, rehabilitation therapists, nutritionists and social workers. They work in collaboration with surgeons to provide a range of diagnostic, technical, therapeutic, cardiac care and support services to the patients and their families.Some allied health professions are more specialized. They must adhere to national training and education standards and their professional scope of practice. For example, the training of perfusionists consists of at least five years of academic in medical schools and another three-year-long clinical training in the hospital. The cardiac intensivists usually are medical doctors with a background in cardiology. They spend 3-4 years rotating in Internal Medicine, Anesthesiology, Emergency Rooms and Intensive Care Units. There have specialized medical societies to grant certified credentials and to provide continuing education. Other allied health professions require no special training or credentials and are trained for their work by the hospitals through on-the-job training. Many young health care providers are getting involved in the allied health personnel projects. They consider this as a career ladder because of the opportunities for advancement within specific fields.


Total control of fat cells from adipogenesis to apoptosis using a xanthene analog.
Overcrowded adipocytes secrete excess adipokines and cytokines under stress, which results in a deregulated metabolism. This negative response to stress increases the possibility of obesity and several of its associated diseases, such as cancer and atherosclerosis. Therefore, a reduction in the number of adipocytes may be a rational strategy to relieve the undesired expansion of adipose tissue. A newly synthesized xanthene analog, MI-401, was found to have two distinct effects on the regulation of the adipocyte's life cycle. MI-401 efficiently down regulated the expression of transcription factors, PPARγ and C/EBPα, and lipogenesis proteins, FAS and FABP4. This down regulation resulted in the inhibition of adipogenesis. Without newly differentiated adipocytes, the total number of adipocytes will not increase. In addition to this inhibitory effect, MI-401 was able to actively kill mature adipocytes. It specifically triggered apoptosis in adipocytes at low micro molar concentration and spared preadipocytes and fibroblasts. These dual functionalities make MI-401 an effective agent in the regulation of the birth and death of adipocytes.


Nonferromagnetic material inserted magnetostrictive patch bonding technique for torsional modal testing of a ferromagnetic cylinder.
Torsional vibration testing requires pure torsional mode transduction. However, no reliable technique is available for exciting torsional vibrations in ferromagnetic cylinders for a relatively wide range of frequencies. A magnetostrictive patch bonding excitation method developed for nonferromagnetic cylinders, based on the magnetostrictive principle, may be considered for ferromagnetic cylinders. However, the direct bonding of a magnetostrictive patch onto a ferromagnetic cylinder fails because the applied magnetic field spreads to both the patch and the cylinder and thus generates unwanted modes of vibration such as longitudinal modes. Thus, a modified or new technique must be developed in order to concentrate the applied magnetic field mainly on the patch, while causing the patch deformation to fully transfer to the cylinder. This paper presents a modified magnetostrictive patch bonding excitation and measurement technique suitable for ferromagnetic cylinders. The key idea is to insert a nonferromagnetic material between the test cylinder and the magnetostrictive patch. Because the thickness of the material or the gap size critically affects the torsional vibration test by the magnetostrictive patch bonding method, a series of numerical and experimental investigations to find the optimal gap size are conducted. Other factors affecting the developed modal testing method are also considered. The validity of the developed method is checked by comparing the experimentally obtained eigenfrequencies of a test ferromagnetic cylinder with the theoretical eigenfrequencies.


Metamorphosis in Xenopus laevis is not associated with large-scale nuclear DNA content variation.
Amphibian metamorphosis is a complex process that has been speculated to involve DNA amplification and chromatin rearrangement. While recent studies have concentrated on chromatin rearrangement, only a few studies have dealt with variation in the amount of DNA during amphibian metamorphosis. In this study, nuclei were isolated from Xenopus laevis at various developmental stages. The nuclei were examined in both an unfixed state and a fixed state. The nuclei were stained with propidium iodide and analyzed by flow cytometry to determine their fluorescence intensity. The unfixed nuclei had higher fluorescence variation compared with the fixed nuclei. This increase in variation appeared due to the presence of nuclei of variable fluorescence intensity within the unfixed nuclei. Upon optimum fixation, which has been speculated to result in more homogeneous chromatin conformation and to reduce staining artifacts, the nuclei were observed to have less fluorescence intensity variation. The differential fluorescence observed in this study is consistent with the hypothesis that large-scale intra-individual DNA variation is not associated with amphibian metamorphosis.


Contraceptive efficacy of a depot progestin and androgen combination in men.
WHO studies provided proof of concept for hormonal male contraception using a prototype androgen-alone regimen. Combined testosterone plus progestin regimens offer more practical promise, but no contraceptive efficacy studies have been completed. The objective of this study was to establish the proof of principle for depot hormonal androgen/progestin combination as a male contraceptive. We performed a contraceptive efficacy study of 55 healthy men in stable fertile relationships seeking a change in contraceptive method. Testosterone (four 200-mg implants, every 4 or 6 months) and 300 mg depot medroxyprogesterone acetate, im, every 3 months were administered. Once sperm output was suppressed (<1 million/ml for 2 consecutive months), men entered a 12-month contraceptive efficacy period, ceasing other contraception. The main outcome measure was contraceptive failure (pregnancy) rate. No pregnancies occurred in 426 person-months (35.5 person-years; 95% confidence limits for contraceptive failure rate, 0-8%/annum), superior to the first year failure rate of condoms, the only reversible male method. Sperm density fell rapidly, so 94% of men entered the efficacy phase by 3 months, with only 2 of 55 (3.6%) men not sufficiently suppressed to enter efficacy. A few men treated with testosterone implants at 6-month intervals demonstrated androgen deficiency symptoms and/or escape of gonadotropin and spermatogenic suppression between months 5 and 6; after a protocol amendment, all men receiving testosterone implants at 4-month intervals avoided androgen deficiency or loss of gonadotropin and sperm output suppression. Recovery was complete (median, 3.6 months to sperm reappearance and 5.0 months to 20 million sperm/ml) in all but one man with an incidental testicular disorder. Discontinuations were for protocol-related reasons (n = 15) or altered personal circumstances (n = 12), but there were no serious adverse effects related to drug exposure. The first male contraceptive efficacy study using a prototype depot androgen/progestin combination demonstrates high contraceptive efficacy with satisfactory short-term safety and recovery of spermatogenesis. Further studies of purpose-developed products are required to extend the overall safety and efficacy experience with depot androgen/progestin combinations, the most promising approach to hormonal male contraception.


Decreased physical effort, fatigue, and mental distress in patients with coronary artery disease: importance of personality-related differences.
Identification of cardio-toxic psychological symptoms in coronary artery disease (CAD) patients is important. We examined the association of negative affectivity (NA), social inhibition (SI), and their combination in the distressed (Type D) personality with functional status, fatigue, and mental distress in CAD patients. Following acute coronary syndrome, 690 consecutive CAD patients agreed to participate in this cross-sectional study and were evaluated for clinical characteristics, including left ventricular ejection fraction (LVEF), and for NA, SI, and Type D personality (i.e., NA and SI; DS14 scale) when they entered a cardiac rehabilitation program in Lithuania. Patient-centered outcomes included functional status (bicycle ergometer), symptoms of fatigue (Multidimensional Fatigue Inventory-20), and mental distress (Beck Depression Inventory-II and Hospital Anxiety and Depression Scale). The reference subgroup (neither NA nor SI) included 34 % of patients; 13 % had NA only, 19 % had SI only, and 34 % had Type D profile. Type D patients had worse functional status, and Type D patients and NA-only patients had higher symptom levels of fatigue and mental distress. In multivariate regression models that included LVEF, clinical characteristics, and depressive symptoms, Type D personality was an independent predictor of decreased exercise capacity (OR = 1.77, 95 % CI 1.06-2.95, p = .03) and decreased motivation for activity (OR = 3.14, 95 % CI 1.73-5.73, p < .001). Type D, NA, and SI were also independent predictors of mental distress. Type D personality traits independently predicted poor functional status and worse patient-centered outcomes independently from LVEF and depression. Further studies exploring personality-related differences in cardiovascular outcomes are needed.


Santocellus (Neuroptera, Chrysopidae, Leucochrysini): taxonomic changes, new description, and a key to the species.
Santocellus is a small Neotropical genus of leucochrysine lacewings that only recently was separated from Leucochrysa. Here, the features of the Leucochrysa risi Esben-Petersen holotype (a female) are described and shown to support the species' transfer to Santocellus and the continued retention of the genus Santocellus as separate from Leucochrysa. The valid name for the species becomes Santocellus risi (Esben-Petersen, 1933), comb. n., and Santocellus bullata (Tauber, 2007) is recognized as a syn. n. of Santocellus risi. Currently, this species is reported only from Peru. An illustrated key is provided for distinguishing the known species in the genus Santocellus.


Stimulation of macrophages by muroctasin to produce colony-stimulating factors.
Murocatasin (N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine, MDP-Lys(L18], a muramyl dipeptide derivative, has been reported to increase the number of peripheral granulocytes and monocytes after subcutaneous administration to animals and humans. When macrophage cell lines such as P388D1 and J774.1 cells were incubated with muroctasin in vitro, the production of colony-stimulating factor (CSF) from these cells was increased significantly. By Northern blot analysis, expression of the M-CSF gene, but not the G-CSF gene, in these macrophage cell lines was found to be enhanced by treatment with muroctasin. However, expression of the G-CSF gene in NFSA cells, a fibrosarcoma cell line established as a G-CSF producer, was actually enhanced by incubation with the conditioned medium from P388D1 cells stimulated with muroctasin. Thus, the hematopoietic activity of muroctasin was suggested to be attributable primarily to the enhanced production of M-CSF from macrophages. The enhanced G-CSF production from NFSA cells may be due at least to interleukin-1 released from muroctasin-stimulated macrophages.


Lewis Acid-Catalyzed 1,4-Addition and Annulation of 4-Hydroxy-coumarins with o-Hydroxyphenyl Propargyl Amines: Entry to Regio-Selective Synthesis of Furano[3,2-c]coumarins and Pyrano[3,2-c]coumarins.
A facile and regioselective Lewis acid-catalyzed cascade annulation of o-hydroxyphenyl propargyl amines with 4-hydroxycoumarin to afford furano[3,2-c]coumarin and pyrano[3,2-c]coumarin derivatives is reported. The reaction presumably proceeds by the conjugate addition of 4-hydroxycoumarin to the in situ-generated alkynyl o-quinone methide and is followed by intramolecular 5-exo-dig and 6-endo-dig annulation to form furano[3,2-c]coumarins and pyrano[3,2-c]coumarins, respectively. The prepared o-hydroxyl substituted pyrano[3,2-c]coumarins could be readily transformed into the corresponding coumarin-derived dioxabicycles by acid-mediated cyclization.


Respiratory adaptations in a deep-sea orbiniid polychaete from Gulf of Mexico brine pool NR-1: metabolic rates and hemoglobin structure/function relationships.
Methanoaricia dendrobranchiata Blake (Polychaeta; Orbiniidae) occurs in large numbers in association with communities of the mussel Bathymodiolus childressi at hydrocarbon seeps on the Louisiana Slope of the Gulf of Mexico. Its microhabitat can be strongly hypoxic (oxygen is often undetectable) and sulfidic (sulfide concentrations can reach millimolar levels), which may seriously challenge aerobic metabolism. We describe a suite of adaptations to its low-oxygen environment. The worms are capable of regulating their rate of oxygen consumption down to partial pressures of approximately 870 Pa oxygen. This capability correlates with a large gill surface area, a small diffusion distance from sea water to blood, a very high hemoglobin oxygen-affinity (P50=27.8 Pa at 10 degrees C and pH 7.6) and a Bohr effect that is pronounced at high oxygen saturations. When fully saturated, the hemoglobin binds sufficient oxygen for only 31 min of aerobic metabolism. However, these polychaetes can withstand extended periods of anoxia both in the absence and presence of 1 mmol l(-1) sulfide (TL50=approx. 5.5 and 4 days, respectively).


Gamma rays from ultracompact primordial dark matter minihalos.
Ultracompact minihalos have been proposed as a new class of dark matter structure. They would be produced by phase transitions in the early Universe or features in the inflaton potential, and constitute nonbaryonic massive compact halo objects today. We examine the prospects of detecting these minihalos in gamma rays if dark matter can self-annihilate. We compute present-day fluxes from minihalos produced in the e{+}e{-} annihilation epoch and the QCD and electroweak phase transitions. Even at a distance of 4 kpc, minihalos from the e{+}e{-} epoch would be eminently detectable today by the Fermi satellite or air Cerenkov telescopes, or even in archival EGRET data. Within 2 kpc, they would appear as extended sources to Fermi. At 4 kpc, minihalos from the QCD transition have similar predicted fluxes to dwarf spheroidal galaxies, so might also be detectable by present or upcoming experiments.


[Management of visceral artery aneurysms. Retrospective study of 23 cases].
To evaluate symptoms and results of the treatment of aneurysms of digestive arteries. Retrospective study of 23 patients (14 male and 9 female, mean age = 51 years) treated in two departments of academic hospital. We studied the aneurysms characteristics (location, number, size, etiology) the type of treatment, and occurrence of post-operative complications. The aneurysms involved the splenic artery in 13 patients (56%), the superior mesenteric artery in 5 patients (22%), the hepatic artery in 3 patients (13%), the gastroepiploic artery in 2 patients (9%). There were thirty-one aneurysms (24 true aneurysms and 7 pseudo-aneurysms) in 23 patients. Diagnosis was mainly done by the CT-scan. An aneurysm rupture occurred in 7 patients (30%). Treatment was surgery for 26 aneurysms (84%) or a radiological embolization in 3; abstention was decided for 2 aneurysms (6%). No death was observed. The bad prognosis after rupture, the lack of predictive factors of rupture combined with the good results of surgical treatment suggest to prefer a surgical treatment at first. Embolization could be reserved for the contra-indication of surgery and when aneurysms are poorly accessible to surgery.


Male and Female Ministers: Comparing Roman Catholic and Methodist Deacons on Personality Structure, Religious Beliefs, and Leadership Styles.
Christian deacons (50 Roman Catholic; 50 Methodist) self-reported their personality, religiosity, and leadership attributes, plus social desirability tendencies. There were no significant correlates between social desirability and any of these self-reported variables. Results also found no significant differences across Christian denominations on personality dimensions, religious and spirituality beliefs, or leadership styles. Also, there were no significant differences in self-reported personality, religiosity, or leadership among Catholic male deacons with Methodist female deacons only ( n = 43). Taken together, in the present exploratory study across denomination and gender, Christian deacons view themselves similarly in personality, religiosity, and overall leadership characteristics.


Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling.
The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newborns. We previously reported that constitutive Toll-like receptor (TLR) 4 expression and cytokine secretion on lipopolysaccharide (LPS) stimulation increases with gestational age. Here, we analyzed constitutive monocyte TLR2 expression and evaluated the expression profiles of the proximal downstream adapter molecule myeloid differentiation factor 88 (MyD88). We further investigated activation of protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14 monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and lipoteichoic acid [LTA]). The functional outcome of the stimulation was determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12 adults were investigated. In contrast to TLR4 expression, TLR2 levels did not differ between age groups. However, MyD88 levels were significantly lower in preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age groups after stimulation with TLR-specific ligands. Accordingly, after LTA stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine production were substantially lower (P<.001) in preterm newborns than in adults. The reduced functional response to bacterial cell wall components appears to be part of the functional immaturity of the neonatal immune system and might predispose premature newborns to bacterial infection.


A case of impaired naming and knowledge of body parts. Are limbs a separate sub-category?
A left hemisphere stroke patient presented a disproportionate difficulty for body parts knowledge without autotopagnosia. The deficit concerned the lexical-semantic representation of body parts and was most severe for limbs. The ability to gesture was spared and action naming was not more impaired than object naming. On the basis of normal naming latencies, we conclude that limbs are the most vulnerable component of the overall category of body parts. This vulnerability is not explained by unbalanced nuisance variables. More cognitive effort is probably required for the appropriate differentiation of limbs during semantic processing and lexical access.


Acceptance and Commitment Therapy: A Transdiagnostic Behavioral Intervention for Mental Health and Medical Conditions.
Psychological interventions have a long history of successful treatment of patients suffering from mental health and certain medical conditions. At the same time, psychotherapy research has revealed key areas of growth for optimizing patient care. These include identifying novel treatment delivery methods that increase treatment adherence, developing new strategies to more effectively address the ever-growing population of patients with comorbid conditions, and elucidating the mechanisms by which effective treatments work in order to further refine their design. Acceptance and commitment therapy (ACT) is an empirically supported psychotherapy that offers promise for patients suffering from a wide range of mental and physical conditions, while addressing these gaps and challenges in the field. ACT rests on the fundamental premise that pain, grief, disappointment, illness, and anxiety are inevitable features of human life, with the therapeutic goal of helping individuals productively adapt to these types of challenges by developing greater psychological flexibility rather than engaging in counterproductive attempts to eliminate or suppress undesirable experiences. This is achieved through committed pursuit of valued life areas and directions, even in the face of the natural desire to escape or avoid painful and troubling experiences, emotions, and thoughts. ACT is transdiagnostic (applies to more than one condition), process-focused, and flexibly delivered. In a relatively short period of time, ACT has been effectively implemented across a broad range of therapeutic settings, including mental health, primary care, and specialty medical clinics. ACT has also been delivered in a variety of formats, including 1-day group workshops, online and smartphone applications, and telehealth. Focus on how best to package and deliver treatment to meet the unique needs of different patient populations helps to ensure treatment adherence and has fostered successful application of ACT for patients in everyday clinical settings.


Molecular dynamics of conformation-specific dopamine transporter-inhibitor complexes.
The recreational psychostimulant cocaine inhibits dopamine reuptake from the synapse, resulting in excessive stimulation of postsynaptic dopamine receptors in brain areas associated with reward and addiction. Cocaine binds to and stabilizes the outward- (extracellular-) facing conformation of the dopamine transporter (DAT) protein, while the low abuse potential DAT inhibitor benztropine prefers the inward- (cytoplasmic-) facing conformation. A correlation has been previously postulated between psychostimulant abuse potential and preference for the outward-facing DAT conformation. The 3β-aryltropane cocaine analogs LX10 and LX11, however, differ only in stereochemistry and share a preference for the outward-facing DAT, yet are reported to vary widely in abuse potential in an animal model. In search of the molecular basis for DAT conformation preference, complexes of cocaine, benztropine, LX10 or LX11 bound to each DAT conformation were subjected to 100ns of all-atom molecular dynamics simulation. Results were consistent with previous findings from cysteine accessibility assays used to assess an inhibitor's DAT conformation preference. The respective 2β- and 2α-substituted phenyltropanes of LX10 and LX11 interacted with hydrophobic regions of the DAT S1 binding site that were inaccessible to cocaine. Solvent accessibility measurements also revealed subtle differences in inhibitor positioning within a given DAT conformation. This work serves to advance our understanding of the conformational selectivity of DAT inhibitors and suggests that MD may be useful in antipsychostimulant therapeutic design.


Exploring the mechanism of immediate analgesic effect of 1-time tuina intervention in minor chronic constriction injury rats using RNA-seq.
Previous studies have proved and investigated the mechanism of the analgesic effect of tuina treatment on neuropathic pain. The purpose of this study was to analyze changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after 1-time tuina intervention to investigate the immediate analgesic mechanism by tuina. An improvement in nociceptive behavior in minor chronic constriction injury (CCI) rats after 1-time tuina was observed. 1-time tuina was more effective in the amelioration of thermal hyperalgesia, but no changes were found in the ultrastructure of DRG and SDH. Sixty-five differentially expressed genes (DEGs) modulated by tuina were detected in the DRG and 123 DEGs were detected in the SDH. Potential immediate analgesic mechanisms of tuina were analyzed by the Kyoto Encyclopedia of Genes and Genomes. DEGs were enriched in 75 pathways in DRG, and 107 pathways in SDH. The immediate analgesic mechanism of tuina is related to the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.


Predominantly extraaxial astroblastoma: imaging and proton MR spectroscopy features.
The CT, angiographic, MR, and proton MR spectroscopy findings in a case of astroblastoma, a rare neoplasm of glial cell origin, are presented. Of particular interest is the predominantly extraaxial location of the tumor. CT and MR demonstrated a complex mass consisting of a solid nodule and a peripheral septated cystic component. The extraaxial nature of the mass was suggested on MR.


Erysipelothrix rhusiopathiae, serotype 17, septicemia in moose (Alces alces) from Algonquin park, Ontario.
Erysipelothrix rhusiopathiae septicemia was diagnosed in three of four moose found dead in Algonquin Provincial Park, Ontario, Canada, in the spring of 1989. Type 17 E. rhusiopathiae was isolated from liver, lung, kidney, and lymph nodes of affected animals, which were in poor body condition, and suffering hair loss associated with tick (Dermacentor albipictus) infestations. Microscopic lesions consisted of mild, multifocal, necrotizing myocarditis, sarcocystosis, and lymph node atrophy. The bacterium may have gained entry to these animals via ingestion of, or percutaneous exposure to, contaminated water, or possibly by the bites of ticks. Malnutrition and tick infestation may have predisposed the animals to infection by this opportunistic pathogen.


Assessment of sleep in hospital patients: a review of methods.
Since sleep and healing appear to be associated, achieving the optimum quality of sleep among hospital patients should be a priority for both clinical nurses and researchers. This paper discusses various methods of sleep assessment which may be used by those intending to conduct research in this field.


Inferences for Stress-Strength Reliability Model in the Presence of Partially Accelerated Life Test to Its Strength Variable.
We focus on estimating the stress-strength reliability model when the strength variable is subjected to the step-stress partially accelerated life test. Based on the assumption that both stress and strength random variables follow Weibull distribution with a common first shape parameter, the inferences for this reliability system are constructed. The maximum likelihood, two parametric bootstraps, and Bayes estimates are obtained. Moreover, approximate confidence intervals, asymptotic variance-covariance matrix, and highest posterior density credible intervals are derived. A simulation study and application to real-life data are conducted to compare the proposed estimation methods developed here and also check the accuracy of the results.


[Not Available].
During the last decades, medical historiography has undergone considerable changes. This review attempts an outline of the developments since 1945. The first section sketches the institutional background of the discipline focusing on the characteristic features which emerged in different national traditions. The following sections - essentially restricted to the German speaking context - describe the development of the fields in research and teaching, ranging from the history of ideas to the social history of medicine, from philological and editorial work to the philosophy and sociology of medical knowledge.


Draft Whole-Genome Sequence of a Novel Chryseobacterium viscerum Strain Isolated from Fresh Water at Dripping Springs, New Mexico.
We sequenced the genome of a bacterial species recently isolated from fresh water at Dripping Springs, NM, and identified it as Chryseobacterium viscerum This species had previously been isolated only from dead or diseased fish. This report shows that C. viscerum can be found in nature as a free-living species not associated with diseased fish.


Physician assistants and nurse practitioners. American College of Physicians.
This position paper by the American College of Physicians Task Force on Physician Supply examines expanded roles for physician assistants and nurse practitioners in light of projected shortages of primary health care providers. Meta-analyses and other literature reviews comparing the care provided by nurse practitioners and physician assistants with that by primary care physicians had methodologic shortcomings that made the data difficult to interpret. There were no studies comparing nurse practitioners in independent practice with physicians. Seven policy positions are articulated.


Simulation and estimation of gene number in a biological pathway using almost complete saturation mutagenesis screening of haploid mouse cells.
Genome-wide saturation mutagenesis and subsequent phenotype-driven screening has been central to a comprehensive understanding of complex biological processes in classical model organisms such as flies, nematodes, and plants. The degree of "saturation" (i.e., the fraction of possible target genes identified) has been shown to be a critical parameter in determining all relevant genes involved in a biological function, without prior knowledge of their products. In mammalian model systems, however, the relatively large scale and labor intensity of experiments have hampered the achievement of actual saturation mutagenesis, especially for recessive traits that require biallelic mutations to manifest detectable phenotypes. By exploiting the recently established haploid mouse embryonic stem cells (ESCs), we present an implementation of almost complete saturation mutagenesis in a mammalian system. The haploid ESCs were mutagenized with the chemical mutagen N-ethyl-N-nitrosourea (ENU) and processed for the screening of mutants defective in various steps of the glycosylphosphatidylinositol-anchor biosynthetic pathway. The resulting 114 independent mutant clones were characterized by a functional complementation assay, and were shown to be defective in any of 20 genes among all 22 known genes essential for this well-characterized pathway. Ten mutants were further validated by whole-exome sequencing. The predominant generation of single-nucleotide substitutions by ENU resulted in a gene mutation rate proportional to the length of the coding sequence, which facilitated the experimental design of saturation mutagenesis screening with the aid of computational simulation. Our study enables mammalian saturation mutagenesis to become a realistic proposition. Computational simulation, combined with a pilot mutagenesis experiment, could serve as a tool for the estimation of the number of genes essential for biological processes such as drug target pathways when a positive selection of mutants is available.


Validated HPLC method for the quantitative determination of CoQ(10) in dog plasma and its application to a pharmacokinetic study.
Coenzyme Q(10) (CoQ(10) ) is a naturally occurring compound located in all membranes throughout the cell. A rapid and sensitive HPLC method was developed to determine the concentration of CoQ(10) in dog plasma using a surrogate matrix. Chromatographic separation was carried out on a Diamonsil C(18) column with the UV detector set at 275 nm. Methanol-2-propanol (40:60, v/v) was used as a mobile phase delivered at a flow rate of 1.0 mL/min. Calibrators were prepared using blank plasma-K(2) HPO(4) buffer (50 mm, pH 8.0)-saline (1:3:6, v/v/v) as surrogate matrix. It was shown that the surrogate matrix had similar properties to dog plasma for CoQ(10) in extraction, freeze-thaw and stability. The assay was linear over the concentration range of 0.10-100 µg/mL. The intra- and inter-day precisions were within 13.3% in terms of relative standard deviation (RSD%) and the accuracy was within ±7.5% in terms of relative error. This simple and reproducible HPLC method with less plasma volume (0.4 mL) and adequate sensitivity was successfully applied to pharmacokinetic studies of CoQ(10) in dogs and an investigation of the effect of CoQ(10) formulation on CoQ(10) baseline levels.


[Comparative investigations on the efficacy of tap water, some detergents and ethanol on the transient flora of the hands (author's transl)].
The germ reducing efficacy of tap water, soap, pHisoHex, pHisoDerm and 70% ethanol was compared using the model of hands artificially contaminated with E. coli. Each of ten persons washed 1, 2 or 4 minutes. Reduction factors were calculated from pre- and post-values and were compared for each individual. After one minute the logarithms of the geometric means of the reduction factors amounted to 2,99, 3,23, 3,28, 3,61, 4,25 in the above used sequence (Table 2). After one minute the reductions came off more slowly and the slopes were linear and parallel as far as the mechanical germ reducing procedures are concerned (Fig. 2). In contrast, ethanol caused a steeper slope even after one minute wash. The strong reduction achieved by mechanical procedures (even with water for one minute 3 powers of ten were observed) demonstrates the high hygienic importance of hand washings for removal of the transient flora. Detergents like pHisoDerm produce further significantly higher reductions and seem to be more suitable than aggressive disinfectants for application in fields where bactericidal action is not imperative. The proposals for procedures aiming at disinfecting of the transient flora issued by the Austrian Society for Hygiene, Microbiology and Preventive Medicine require a reduction factor of at least 10(5) after two minutes hand wash. The results of this investigation show that this is practicable with ethanol and necessary, otherwise the bactericidal action would not be different from a mechanical removal of the transient flora.


Force cycles and force chains.
We examine the coevolution of N cycles and force chains as part of a broader study which is designed to quantitatively characterize the role of the laterally supporting contact network to the evolution of force chains. Here, we elucidate the rheological function of these coexisting structures, especially in the lead up to failure. In analogy to force chains, we introduce the concept of force cycles: N cycles whose contacts each bear above average force. We examine their evolution around force chains in a discrete element simulation of a dense granular material under quasistatic biaxial loading. Three-force cycles are shown to be stabilizing structures that inhibit relative particle rotations and provide strong lateral support to force chains. These exhibit distinct behavior from other cycles. Their population decreases rapidly during the initial stages of the strain-hardening regime-a trend that is suddenly interrupted and reversed upon commencement of force chain buckling prior to peak shear stress. Results suggest that the three-force cycles are called upon for reinforcements to ward off failure via shear banding. Ultimately though, the resistance to buckling proves futile; buckling wins under the combined effects of dilatation and increasing compressive load. The sudden increase in three-force cycles may thus be viewed as an indicator of imminent failure via shear bands.


The long-term clinical impact of biochemical recurrence of prostate cancer 5 or more years after radical prostatectomy.
Information regarding the clinical impact of delayed (5 years or greater) biochemical failure (BF) after radical prostatectomy (RP) is lacking. We undertook an investigation to differentiate the innocuous recurrence of serum prostate specific antigen (PSA) from that which heralds an eventual clinical failure (CF), and to determine if there is a period following RP when a patient is cured of clinical disease. Men with clinically localized prostate cancer (PCA) undergoing RP (1987 to 1995) were identified from our longitudinal PCA registry. Outcome measurements were based on the detection of post-RP serum PSA 0.4 ng/ml or greater, clinical identification of cancer recurrence and disease related death. Following RP in 3,903 eligible men, 33% had a detectable PSA (median followup 8.8 years). Of these BFs 27% occurred after 5 or more disease-free years. Currently, 29% of all men with BF have clinical evidence of PCA, with 8% dying of PCA (median actuarial survival time from CF to death 9.8 years). Progression from BF to CF was not significantly altered by the disease-free interval (p = 0.544). A PSA doubling time less than 12 months significantly increased the risk of CF regardless of the interval from surgery. Risk factors for BF were significant throughout the duration of followup. Patients are at prolonged risk for BF and CF following RP. Regardless of the timing of the initial PSA recurrence the PSA doubling time is the most powerful predictor of progression, stratifying patients with BF into high and low risk groups for CF.


Accessory mental foramen.
Accessory mental foramen is a rare anatomical variation. Even so, in order to avoid neurovascular complications, particular attention should be paid to the possible occurrence of one or more accessory mental foramen during surgical procedures involving the mandible. A 3-dimensional computed tomography (3D-CT) scan of a female patient revealed an accessory mental foramen on the right side of her mandible. A 3D-CT scan should be obtained prior to mandibular surgeries so that the presence of accessory mental foramen can be detected, and so that the occurrence of a neurosensory disturbance or hemorrhage can be avoided. Although this anatomical variation is rare, it should be kept in mind that an accessory mental foramen may exist.


Hate in the counter-transference.
An analyst has to display all the patience and tolerance and reliability of a mother devoted to her infant, has to recognize the patient's wishes as needs, has to put aside other interests in order to be available and to be punctual, and objective, and has to seem to want to give what is really only given because of the patient's needs.There may be a long initial period in which the analyst's point of view cannot be (even unconsciously) appreciated by the patient. Acknowledgment cannot be expected because at the primitive root of the patient that is being looked for there is no capacity for identification with the analyst, and certainly the patient cannot see that the analyst's hate is often engendered by the very things the patient does in his crude way of loving.In the analysis (research analysis) or in ordinary management of the more psychotic type of patient, a great strain is put on the analyst (psychiatrist, mental nurse) and it is important to study the ways in which anxiety of psychotic quality and also hate are produced in those who work with severely ill psychiatric patients. Only in this way can there be any hope of the avoidance of therapy that is adapted to the needs of the therapist rather than to the needs of the patient.


Molecular cloning of a recA-like gene from the cyanobacterium Anabaena variabilis.
A recA-like gene isolated from the cyanobacterium Anabaena variabilis was cloned and partially characterized. When introduced into Escherichia coli recA mutants, the 7.5-kilobase-pair plasmid-borne DNA insert restored resistance to methyl methanesulfonate and UV irradiation, as well as recombination proficiency when measured by Hfr-mediated conjugation. The cyanobacterial recA gene restored spontaneous but not mitomycin C-induced prophage production. Restriction analysis and subcloning yielded a 1.5-kilobase-pair Sau3A fragment which also restored methylmethane sulfonate resistance and coded for a 38- to 40-kilodalton polypeptide when expressed in an in vitro transcription-translation system.


Polymeric nano-micelles: versatile platform for targeted delivery in cancer.
Polymeric micelles are among the most promising delivery systems in nanomedicine. The growing interest in polymeric micelles as drug delivery vehicle is promoted by the advantages they offer for hydrophobic anticancer agents. The size of most polymeric micelles lies within the range 10-100 nm ensuring that they can selectively leave the circulation at tumor site via the enhanced permeability and retention effect. Their unique structure allows them to solubilize hydrophobic drugs, prolongs their circulatory half-life and eventually leads to enhanced therapeutic efficacy. In addition, they can undergo several structural modifications to further augment tumor cell uptake. In this review, we will discuss various micellar systems that have been studied in preclinical and clinical settings.


Using ePrognosis to estimate 2-year all-cause mortality in older women with breast cancer: Cancer and Leukemia Group B (CALGB) 49907 and 369901 (Alliance A151503).
Tools to estimate survival, such as ePrognosis ( http://eprognosis.ucsf.edu/carey2.php ), were developed for general, not cancer, populations. In older patients with breast cancer, accurate overall survival estimates would facilitate discussions about adjuvant therapies. Secondary analyses were performed of data from two parallel breast cancer studies (CALGB/Alliance 49907/NCT000224102 and CALGB/Alliance 369901/NCT00068328). We included patients (n = 971) who were age 70 years and older with complete baseline quality of life data (194 from 49907; 777 from 369901). Estimated versus observed all-cause two-year mortality rates were compared. ePrognosis score was calculated based on age, sex, and daily function (derived from EORTC QLQ-C30). ePrognosis scores range from 0 to 10, with higher scores indicating worse prognosis based on mortality of community-dwelling elders and were categorized into three groups (0-2, 3-6, 7-10). Observed mortality rates were estimated using Kaplan-Meier methods. Patient mean age was 75.8 years (range 70-91) and 73% had stage I-IIA disease. Most patients were classified by ePrognosis as good prognosis (n = 562, 58% 0-2) and few (n = 18, 2% 7-10) poor prognosis. Two-year observed mortality rates were significantly lower than ePrognosis estimates for patients scoring 0-2 (2% vs 5%, p = 0.001) and 3-6 (8% vs 12%, p = 0.01). The same trend was seen with scores of 7-10 (23% vs 36%, p = 0.25). ePrognosis tool only modestly overestimates mortality rate in older breast cancer patients enrolled in two cooperative group studies. This tool, which estimates non-cancer mortality risk based on readily available clinical information may inform adjuvant therapy decisions but should be validated in non-clinical trial populations.


Determination of aminoglutethimide and N-acetylaminoglutethimide in human plasma by reversed-phase liquid chromatography.
A liquid chromatography method for the determination of aminoglutethimide and N-acetylaminoglutethimide in human plasma is described. The assay involved precipitation of the plasma proteins using a mixture of acetonitrile and perchloric acid, without an extraction procedure. The supernatant was subjected to chromatography on a 3-micrometers ODS Hypersil column eluted isocratically with 11% acetonitrile in 100 mM ammonium formate buffer, pH 3.5. The absorbance was routinely recorded at 242 nm. The standard curves were linear in the range of 0.1-100 micrograms/ml, and the lower detection limit was approximately 0.1 microgram/ml for aminoglutethimide and its plasma metabolite N-acetylaminoglutethimide. The precision of the method, given as the coefficient of variation, was 3.9%. With this method, it was determined that aminoglutethimide and N-acetylaminoglutethimide were present in the plasma of patients receiving single-dose or continuous treatment with aminoglutethimide for breast cancer. No N-formylaminoglutethimide or nitroglutethimide could be demonstrated in the plasma from these patients. Interference from several drugs commonly given to patients with breast cancer was ruled out.


An approach to estimation in relative survival regression.
The goal of relative survival methodology is to compare the survival experience of a cohort with that of the background population. Most often an additive excess hazard model is employed, which assumes that each person's hazard is a sum of 2 components--the population hazard obtained from life tables and an excess hazard attributable to the specific condition. Usually covariate effects on the excess hazard are assumed to have a proportional hazards structure with parametrically modelled baseline. In this paper, we introduce a new fitting procedure using the expectation-maximization algorithm, treating the cause of death as missing data. The method requires no assumptions about the baseline excess hazard thus reducing the risk of bias through misspecification. It accommodates the possibility of knowledge of cause of death for some patients, and as a side effect, the method yields an estimate of the ratio between the excess and the population hazard for each subject. More importantly, it estimates the baseline excess hazard flexibly with no additional degrees of freedom spent. Finally, it is a generalization of the Cox model, meaning that all the wealth of options in existing software for the Cox model can be used in relative survival. The method is applied to a data set on survival after myocardial infarction, where it shows how a particular form of the hazard function could be missed using the existing methods.


Phosphorylation of the MAPK pathway has an essential role in the acrosome reaction in miniature pig sperm.
In almost all animal species, sperm acrosome reaction (AR) is a crucial step for fertilization. The step is a Ca(2+)-dependent secretory event that must be completed before fertilization. Many researchers have reported that several chemicals (such as ionomycin, thapsigargin and caffeine) artificially induce this step by increasing [Ca(2+)](i). However, little information has been known on events that occur following Ca(2+) induced initiation of the sperm AR. We show here for the first time that phosphorylation of the mitogen-activated protein kinase (MAPK) pathway is required for the AR in miniature pig sperm. Following caffeine treatment artificially inducing the AR in miniature pig sperm, Raf was phosphorylated and then MAP kinase kinase (MEK) and extracellular-signal regulated kinase 1 (ERK1) were also phosphorylated in a time-dependent manner. However, the total ERK1 level did not change during the culture. Pre-treatment of sperm with U0126, a MEK inhibitor, significantly suppressed both the AR and phosphorylation of MEK/ERK1 in a dose-dependent manner. Additionally, pre-incubation of the sperm with seminal vesicle (SV) fluid, which is known to contain a decapacitation factor, suppressed both the AR and MEK/ERK1 phosphorylation. These results suggest that phosphorylation of MAPK pathway plays an important role in the AR in miniature pig sperm. Moreover, the SV fluid may have an inhibitory effect on the AR via the suppression of the MAPK pathway.


Dissolved inorganic carbon speciation in aquatic environments and its application to monitor algal carbon uptake.
Dissolved inorganic carbon (DIC) speciation is an important parameter that enables chemical and ecological changes in aquatic environments, such as the aquatic environmental impact of increasing atmospheric CO2 levels, to be monitored. We have examined and developed a sensitive and cost-effective 'back-titration' method to determine the DIC species and abundance in aqueous environments that is more accurate and reproducible than existing methods and is applicable in a range of fresh, brackish and sea waters. We propose the use of pHHCO3 (bicarbonate-dominant pH) and pH3.5 as the titration end points in the back-titration technique to accurately determine carbonate alkalinity. The proposed method has a higher accuracy and precision than other modified Gran's methods that are currently in use. The detection limit was found to be ~5 μmol kg(-1) with an accuracy within 1% and a precision (CV) within 0.2% and 0.5% at high and low level of carbonates, respectively. This method was successfully applied to monitor DIC in the aqueous medium of Nannochlopsis salina cultivation separately carried out with NaHCO3 and CO2 as the respective inorganic carbon source. The cells were able to grow in the NaHCO3 medium with a similar growth curve to cells with 0.039% CO2 (air). Increases in CO2 level stimulated lipid accumulation by diverting the fixed carbon from protein to lipids. The increased concentration of gaseous CO2 and the accompanying lower pH appears to significantly inhibit the growth of algae despite the presence of HCO3(-) when 20% CO2 was employed.


Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study.
In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement).


Child-Adult Differences in Using Dual-Task Paradigms to Measure Listening Effort.
The purpose of the project was to investigate the effects modifying the secondary task in a dual-task paradigm to measure objective listening effort. To be specific, the complexity and depth of processing were increased relative to a simple secondary task. Three dual-task paradigms were developed for school-age children. The primary task was word recognition. The secondary task was a physical response to a visual probe (simple task), a physical response to a complex probe (increased complexity), or word categorization (increased depth of processing). Sixteen adults (22-32 years, M = 25.4) and 22 children (9-17 years, M = 13.2) were tested using the 3 paradigms in quiet and noise. For both groups, manipulations of the secondary task did not affect word recognition performance. For adults, increasing depth of processing increased the calculated effect of noise; however, for children, results with the deep secondary task were the least stable. Manipulations of the secondary task differentially affected adults and children. Consistent with previous findings, increased depth of processing enhanced paradigm sensitivity for adults. However, younger participants were more likely to demonstrate the expected effects of noise on listening effort using a secondary task that did not require deep processing.


Association of Medical Directors of Information Systems consensus on inpatient electronic health record documentation.
In 2013, electronic documentation of clinical care stands at a crossroads. The benefits of creating digital notes are at risk of being overwhelmed by the inclusion of easily importable detail. Providers are the primary authors of encounters with patients. We must document clearly our understanding of patients and our communication with them and our colleagues. We want to document efficiently to meet without exceeding documentation guidelines. We copy and paste documentation, because it not only simplifies the documentation process generally, but also supports meeting coding and regulatory requirements specifically. Since the primary goal of our profession is to spend as much time as possible listening to, understanding and helping patients, clinicians need information technology to make electronic documentation easier, not harder. At the same time, there should be reasonable restrictions on the use of copy and paste to limit the growing challenge of 'note bloat'. We must find the right balance between ease of use and thoughtless documentation. The guiding principles in this document may be used to launch an interdisciplinary dialogue that promotes useful and necessary documentation that best facilitates efficient information capture and effective display.


The implantation chamber, blastocyst and blastocyst imprint of the rat; a scanning electron microscope study.
Splitting the uterus longitudinally through implanatation sites makes it possible to obtain access to blastocysts and implantation chambers during stages of implanatation of the blastocyst in the rat. On the afternoon of day 5 of pregnancy, blastocysts lie in a shallow antimesometrial depression and tend to fall free of the uterus when the chamber is opened. On day 6, blastocysts are oriented in a mesonmetrial-antimesometrial plane, occupy a distinct implantatopm chamber, and tend to adhere to one side or the other of the uterus, leaving an imprint on the contralateral side. After about noon of day 6, some of the blastocysts split in half laterally, and by day 7 all blastocysts which are exposed are split. In addition to demonstrating increased adhesion of blastocyst to uterine epithelium, the procedure clearly shows the progressive elongation of the imlantation chamber. The embrvonic cell mass is specifically oriented on day 6, and is clasped but not distorted, whereas the abembryonic trophoblast is slightly compressed and indented by the uterine epithelium. The microvilli of the uterine epithelium within the imprint become progressively flattened when compared to the microvilli of the implantation chamber outside of the imprint. The method provides a means of gaining direct access to the surface of uterine epithelium precisely where it has been in association with the blastocyst not only for scanning electron microscopy but also for studies of the properties of the surface constituents.


The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice.
Quercetin, a member of the flavonoid family, is one of the most prominent dietary antioxidants. This study investigates the mechanisms for the effects of quercetin on cultured human RPE cells and in Ccl2/Cx3cr1 double knock-out (DKO) mice, which spontaneously develop progressive retinal lesions mimicking age-related macular degeneration (AMD). In the in vitro experiment, cultured ARPE-19 cells were exposed to 1 mM H(2)O(2) with or without 50 muM quercetin for 2 h. Cellular viability, mitochondrial function, and apoptosis were assessed using crystal violet staining, MTT assay, and comet assay, respectively. Apoptotic molecular transcripts of BCL-2, BAX, FADD, CASPASE-3 and CASPASE-9 were measured by RQ-PCR. COX activity and nitric oxide (NO) level were determined in the supernatant of the culture medium. Quercetin treatment protected ARPE-19 cells from H(2)O(2)-induced oxidative injury, enhanced BCL-2 transcript levels, increased the BCL-2/BAX ratio, suppressed the transcription of pro-apoptotic factors such as BAX, FADD, CASPASE-3 and CASPASE-9, inhibited the transcription of inflammatory factors such as TNF-alpha, COX-2 and INOS, and decreased the levels of COX and NO in the culture medium. In the in vivo experiment, DKO and C57/B6 mice were treated with 25 mg/kg/day quercetin by intraperitoneal injection daily for two months. Funduscopy was performed monthly. After two months, serum was collected to measure NADP(+)/NADPH, COX, PGE-2, and NO levels. The eyes were harvested for histology and A2E measurement. Ocular transcripts of Bcl-2, Bax, Cox-2, Inos, Tnf-alpha, Fas, FasL and Caspase-3 were detected by RQ-PCR. Quercetin treatment did not reverse the progression of retinal lesions in DKO mice funduscopically or histologically. Although quercetin treatment could recover systemic anti-oxidative capacity, suppress the systemic expression of NO, COX and PGE-2, and decrease ocular A2E levels, it could not effectively suppress the transcripts of the ocular inflammatory factors Tnf-alpha, Cox-2 and Inos, or the pro-apoptotic factors Fas, FasL and Caspase-3 in DKO mice. Our data demonstrate that quercetin can protect human RPE cells from oxidative stress in vitro via inhibition of pro-inflammatory molecules and direct inhibition of the intrinsic apoptosis pathway. However, quercetin (25 mg/kg/day) does not improve the retinal AMD-like lesions in the Ccl2(-/-)/Cx3cr1(-/-) mice, likely due to its insufficient suppression of the inflammatory and apoptosis pathways in the eye.


Management of a patient with multiple device replacements and extractions: When the leadless pacemaker is a viable solution.
Leadless pacemaker (LPs) is a safe device and the implantation rates of this device is increasing. The device extraction and replacement are today a challenging procedures especially in case of infections, fragile and older patients or in unfavorable venous anatomy; LPs can be a valid alternative strategy in these cases. We report a case of management of a patient with multiple previous device replacements and extractions, with malfunction of transvenous pacemaker and with a fibrous membrane between the walls of the ventricular lead and the superior vena cava (SVC), who underwent a successful LP implantation.


Copper-catalyzed difluoromethylation of propargylamide-substituted indoles: synthesis of mono- and bis-difluoromethylated indoloazepinone derivatives.
A novel copper-catalyzed difluoromethylation of 2- or 3-propargylamide-substituted indoles with ICF2CO2Et via a radical cascade cyclization process is described. A wide substrate scope is compatible with the reaction conditions to synthesize mono- and bis-difluoromethylated indoloazepinone derivatives, which contain a seven-membered ring.


Differential expression of type I hair keratins.
The hair follicle provides an excellent system in which to study growth and differentiation. Hair keratins are useful tissue-specific molecular markers for these events. By comparing a second mouse Type I hair keratin cDNA clone, MHKA-2, with our previously described MHKA-1, we have been able to contrast the nucleotide sequences and corresponding deduced amino acid sequences of the smallest (mHa4) and the largest (mHa1) major Type I hair keratins. Both nucleotide sequences and both deduced amino acid sequences share high identity but have distinct segments suitable for generation of specific molecular probes. Comparison of amino acid sequences adjacent to the central helical domains has demonstrated homologous subdomains, designated H1 and H2, in the Type I hair keratin nonhelical termini. Although there is only 56% amino acid identity in the carboxy-terminal nonhelical domains, a common sequence, T-------CGPC----R, has been identified in this domain, suggesting a possible common functional role for this portion of the molecule. In addition, it appears that mHa4 may differ in part from mHa1 by deletion of a segment between the H2 subdomain and the conserved sequence. Staining of mouse and human hair follicles with AmHa1, a monospecific polyclonal antibody for mHa1, and AE13, an antibody specific for all Type I hair keratins, suggests differential expression of individual Type I hair keratins in both species. This supports our hypothesis that distinct functional requirements are satisfied by the multiplicity of hair keratins.


Subjective sleep inadequacy and self-rated health among homeless adults.
To examine the association between subjective sleep inadequacy and self-rated health in a sample of 244 homeless adults. Logistic regression analyses were conducted to assess associations among 4 sleep inadequacy items (days of inadequate rest or sleep, hours of sleep, days unintentionally falling asleep during daytime, and snoring) and self-rated health in analyses adjusted for age, sex, race, education, lifetime homelessness, lifetime serious mental illness, and current depression. Days of inadequate rest or sleep, fewer hours of sleep, and days unintentionally falling asleep were each significantly associated with higher odds of poor/fair self-rated health. Because both inadequate sleep and poor self-rated health independently predict mortality, interventions targeting sleep quality among homeless adults are needed.


Cyclooxygenase-2 is induced by p38 MAPK and promotes cell survival.
The Na+ ionophore monensin affects cellular pH and, depending on its concentration, causes the survival or death of tumor cells. In the present study, we elucidated the survival pathway activated in U937 cells, a human lymphoma-derived cell line. These cells treated with monensin at a concentration of 5 µM were growth-arrested in G1, activated p38 mitogen-activated protein kinase (MAPK) and showed an increased expression of cyclooxygenase-2 (COX-2). The latter two molecular events were linked, as pharmacological inhibition of the MAPK did not allow COX-2 increased expression. Furthermore, we showed that p38 and COX-2 keep monensin-stressed U937 cells alive, as pharmacological inhibition of each enzyme caused cell death.