Prevalence of rotavirus infection among children with acute diarrhoea after rotavirus vaccine introduction in Kenya, a hospital cross-sectional study.
Rotavirus infection is the most common cause of acute gastroenteritis globally in children under 5 years of age and is responsible for approximately 5% of all child deaths yearly. Rotavirus vaccination is considered an effective public health strategy to prevent infection and reduce the severity of disease. Multi-centre country trials on rotavirus vaccines demonstrated efficacy rates of more than 85% in developed countries but only about 65% in developing nations. Rotavirus vaccination was introduced into the Kenya Expanded Programme on Immunization (KEPI) in 2014. The objective of our study was to determine the prevalence of rotavirus infection, severity of acute diarrhoea and to determine the rotavirus vaccination status among children aged 3-24 months presenting with acute diarrhoea at Kenyatta National Hospital after introduction of rotavirus vaccine in Kenya. A total of 365 children aged 3-24 months presenting with acute diarrhoea at KNH were recruited from August 2016 to April 2017. Data on rotavirus vaccination status, nutritional status, feeding practices and sociodemographic characteristics were obtained and a full clinical evaluation of the patients was done. Severity of the gastroenteritis was assessed using the 20 point Vesikari Clinical Severity Scoring System. The children who were admitted were followed up for 7 days using hospital ward registers. Comorbid conditions were established from patient's clinical records and physical examination. Stool specimens from study participants were tested for rotavirus using a commercially available enzyme linked immunosorbent immunoassay kit- ProSpecT Rotavirus Microplate Assay. Majority of the children (96.7%) had received rotavirus vaccinations. The overall rotavirus prevalence was 14.5% and was higher among 17-24 months at 19.5%. The prevalence somewhat differed by gender, nutritional status, exclusive breastfeeding status, age and education level of mother/caregiver. Overall, a half of the children had severe acute diarrhoea and there were some differences in severity by child/mother characteristics. There is still burden of rotavirus diarrhoea after introduction of rotavirus vaccine and the prevalence varies by child characteristics.


Finite-temperature pairing gap of a unitary fermi gas by quantum monte carlo calculations.
We calculate the one-body temperature Green's (Matsubara) function of the unitary Fermi gas via quantum Monte Carlo, and extract the spectral weight function A(p,omega) using the methods of maximum entropy and singular value decomposition. From A(p,omega) we determine the quasiparticle spectrum, which can be accurately parametrized by three functions of temperature: an effective mass m{*}, a mean-field potential U, and a gap Delta. Below the critical temperature T{c}=0.15 epsilon{F} the results for m{*}, U, and Delta can be accurately reproduced using an independent quasiparticle model. We find evidence of a pseudogap in the fermionic excitation spectrum for temperatures up to T{*} approximately 0.20 epsilon{F}> T{c}.


An immobile postsurgical nasojejunal tube: a case for King Arthur!
A patient was referred to an Endoscopy Unit for removal of a nasojejunal feeding tube that was previously inserted one week before during gastric surgery. Upper endoscopy revealed the nasojejunal tube sutured to the gastric wall and it was then removed with hot biopsy forceps. This case represents an uncommon complication of gastric surgery and highlights that a nasojejunal feeding tube should only be positioned after the suturing procedures and the mobility of the tube should always be tested during surgery.


Electroconvection in a dielectric liquid between two concentric half-cylinders with rigid walls: Linear and nonlinear analysis.
We study the linear stability and nonlinear behavior of the electroconvection between two concentric half-cylinders with no-slip conditions on all boundaries. The no-slip condition makes impossible to apply the standard modal approach. Hence, we apply a finite element technique similar to the one we have used in a previous paper about the electroconvection in a rectangular enclosed domain. When compared to the classical problem of electroconvection between two full concentric cylinders, the linear criterion is higher, due to the viscous shear introduced by the lateral walls. As a consequence, the structure of the eigenmodes is very different. There is a repulsion between modes with the same symmetry, forcing pairs of modes to cross each other repeatedly. For inner injection and small value of the ratio between the inner and outer radii the no-slip condition changes the nature of the bifurcation from subcritical to supercritical, while it is always subcritical for outer injection. To understand this behavior, we perform a modal analysis using the eigenfunctions obtained from the linear stability analysis as modal basis. We show that the supercritical branch is originated by the nonorthogonality of the modes when no-slip boundary conditions are imposed. These mechanism explains the previously unexplained appearance of the supercritical branch in the enclosed rectangular configuration.


Clinical Management of Appendicitis.
Ever since the first appendectomy has been performed, surgery has been the standard of care for acute appendicitis, with antibiotic therapy being reserved for special situations. Recent studies have shown the feasibility of antibiotic therapy for uncomplicated appendicitis. This clinical therapeutic review is based both on author expertise and a selective literature survey in PubMed based on the term 'appendicitis', combined with the terms 'acute', 'complicated', 'conservative', 'non-operative', 'therapy', 'surgery', and 'strategy'. According to these search results as well as to the treatment guidelines from the American College of Surgeons, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, European Association of Endoscopic Surgery, and World Society of Emergency Surgery, we present an interdisciplinary treatment concept. Approximately 90% of patients treated with antibiotics are able to avoid surgery during the initial admission. The other 10% that fail to respond to antibiotics require a rescue appendectomy. Recurrence rates of non-operated patients within 1 year are as high as 20-30%. In uncomplicated appendicitis without risk factors for failure of non-operative management, a shared decision based on the patient's preferences should be made. In cases with risk factors, appendectomy is still the treatment recommended. If the diagnosis is uncertain or clinical symptoms are rather mild, antibiotic therapy should be started. In complicated appendicitis, management depends on the clinical state, with either immediate surgery or primarily antibiotic therapy and combined with drainage of abscess, being followed by interval appendectomy in some cases.


[To improve the cognition about the carcinoma of esophagogastric junction].
Recently, the incidence of carcinoma at the esophagogastric junction (CEG), especially adenocarcinoma at esophagogastric junction (AEG) is increasing. AEG has obvious difference from other parts of stomach tumor in anatomy, physiology and pathology. The scholars have not made a consensus and standard about the treatment of AEG. It is necessary to improve the knowledge and cognition about AEG and find a feasible treatment strategy.


Drosophila glob1 expresses dynamically and is required for development and oxidative stress response.
Biological significance of the globin protein family could be ascertained by their conservation through archaea to human. Globin(s) have been "classically" studied as oxygen binding protein(s), with recent implications in a host of other physiological functions. Drosophila melanogaster possesses three globin genes (glob1, glob2, glob3) located at different cytogenetic positions. We have performed a comprehensive investigation on the cellular expression profile and functional relevance of glob1 in Drosophila development. A profound level of maternally contributed glob1 gene products was found during early embryogenesis. Subsequently, commencement of zygotic transcription leads to its strong expression in somatic muscles, gut primordia, fat bodies, tracheal cells, etc. Similarly, dynamic expression of glob1 was evident in most of the larval tissues, interestingly with high expression in dividing cells. Reduced expression of glob1 leads to various impairments and lethality during embryogenesis and larval development. A substantial increase in level of cellular ROS was also evident due to reduced expression of glob1 which consequently leads to locomotor impairment and early aging in surviving adult flies. To best of our knowledge, this is the first report which demonstrates that in addition to oxygen management, globin gene(s) are also involved in regulating various aspects of development in Drosophila.


Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization.
Transcatheter arterial chemoembolization (TACE) is one of the main palliative therapies for advanced hepatocellular carcinoma (HCC), which is also regarded as a promising therapeutic strategy for cancer treatment. However, drug-loaded microspheres (DLMs), as commonly used clinical chemoembolization drugs, still have the problems of uneven particle size and unstable therapeutic efficacy. Herein, gelatin was used as the wall material of the microspheres, and homogenous gelatin microspheres co-loaded with adriamycin and Fe3O4 nanoparticles (ADM/Fe3O4-MS) were further prepared by a high-voltage electrospray technology. The introduction of Fe3O4 nanoparticles into DLMs not only provided excellent T2-weighted magnetic resonance imaging (MRI) properties, but also improved the anti-tumor effectiveness under microwave-induced hyperthermia. The results showed that ADM/Fe3O4-MS plus microwave irradiation had significantly better antitumor efficacy than the other types of microspheres at both cell and animal levels. Our study further confirmed that ferroptosis was involved in the anti-tumor process of ADM/Fe3O4-MS plus microwave irradiation, and ferroptosis marker GPX4 was significantly decreased and ACSL4 was significantly increased, and ferroptosis inhibitors could reverse the tumor cell killing effect caused by ADM/Fe3O4-MS to a certain extent. Our results confirmed that microwave mediated hyperthermia could amplify the antitumor efficacy of ADM/Fe3O4-MS by activating ferroptosis and the introduction of Fe3O4 nanoparticles can significantly improve TACE for HCC. This study confirmed that it was feasible to use uniform-sized gelatin microspheres co-loaded with Fe3O4 nanoparticles and adriamycin to enhance the efficacy of TACE for HCC.


Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats.
Over the past 20 years, neuroinflammation (NI) has increasingly been recognised as having an important role in many neurodegenerative diseases, including Alzheimer's disease. As such, being able to image NI non-invasively in patients is critical to monitor pathological processes and potential therapies targeting neuroinflammation. The translocator protein (TSPO) has proven a reliable NI biomarker for positron emission tomography (PET) imaging. However, if TSPO imaging in acute conditions such as stroke provides strong and reliable signals, TSPO imaging in neurodegenerative diseases has proven more challenging. Here, we report results comparing the recently developed TSPO tracers [18F]GE-180 and [18F]DPA-714 with (R)-[11C]PK11195 in a rodent model of subtle focal inflammation. Adult male Wistar rats were stereotactically injected with 1 μg lipopolysaccharide in the right striatum. Three days later, animals underwent a 60-min PET scan with (R)-[11C]PK11195 and [18F]GE-180 (n = 6) or [18F]DPA-714 (n = 6). Ten animals were scanned with either [18F]GE-180 (n = 5) or [18F]DPA-714 (n = 5) only. Kinetic analysis of PET data was performed using the simplified reference tissue model (SRTM) with a contralateral reference region or a novel data-driven input to estimate binding potential BPND. Autoradiography and immunohistochemistry were performed to confirm in vivo results. At 40-60 min post-injection, [18F]GE-180 dual-scanned animals showed a significantly increased core/contralateral uptake ratio vs. the same animals scanned with (R)-[11C]PK11195 (3.41 ± 1.09 vs. 2.43 ± 0.39, p = 0.03); [18]DPA-714 did not (2.80 ± 0.69 vs. 2.26 ± 0.41). Kinetic modelling with a contralateral reference region identified significantly higher binding potential (BPND) in the core of the LPS injection site with [18F]GE-180 but not with [18F]DPA-714 vs. (R)-[11C]PK11195. A cerebellar reference region and novel data-driven input to the SRTM were unable to distinguish differences in tracer BPND. Second-generation TSPO-PET tracers are able to accurately detect mild-level NI. In this model, [18F]GE-180 shows a higher core/contralateral ratio and BPND when compared to (R)-[11C]PK11195, while [18F]DPA-714 did not.


Antiretroviral treatment alters relationship between MCP-1 and neurometabolites in HIV patients.
The relationships between neurometabolites and macrophage chemoattractant protein (MCP-1) in serum and cerebrospinal fluid (CSF) were evaluated in HIV patients before and after antiretroviral treatment. Prior studies found higher CSF MCP-1 levels in patients with HIV-associated dementia compared to those in neuroasymptomatic. We hypothesized that CSF MCP-1 levels would correlate inversely to neuronal metabolites [including N-acetyl compounds, glutamate+glutamine, as assessed by principal component analyses (PCA)] and positively to glial metabolites (including myo-inositol and choline compounds). Thirty-nine antiretroviral-naive HIV patients were evaluated prospectively with proton magnetic resonance spectroscopy (1H MRS), and serum and CSF MCP-1 measurements prior to highly active antiretroviral therapy (HAART); 31 of these patients completed follow-up studies after 3 months of HAART but only 24 had follow-up CSF studies. After HAART, brain metabolites and clinical signs showed no change despite improvements in systemic (CD4 counts, plasma viral load, MCP-1) and CSF (viral load and MCP-1) variables. CSF, but not serum, MCP-1 levels correlated inversely with the neuronal component (from PCA) prior to treatment (r=-0.59, P=0.0008). Conversely, after 3 months of HAART, the glial component (from PCA) correlated positively with CSF MCP-1 levels (r=0.70, P=0.0002; ANCOVA interaction for treatment status, P=0.003). These findings suggest that higher CSF MCP-1 levels are associated with neuronal dysfunction in untreated patients. After 3 months of HAART, the decreased systemic factors (viral burden, systemically derived MCP-1) no longer associate with neuronal dysfunction, but subjects with the strongest glial response in the brain continue to produce the highest levels of MCP-1.


Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic beta-cells in experimental diabetes in rats.
Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.


An empirical analysis of eating disorders and anxiety disorders publications (1980-2000)--part I: Research methods.
The current study compared the eating disorder and anxiety disorder literature in terms of research design and methodologic features in 1980, 1990, and 2000. Computer literature searches were conducted using PubMed and PsychInfo databases to identify relevant eating disorder and anxiety disorder articles published at each of the three time points. A total of 456 articles were randomly selected, including 228 articles from the eating disorder literature and the anxiety disorder literature. Within each specific literature, one third (76) of the articles were selected from each of the three time points (1980, 1990, 2000). Two raters, from a team of eight trained raters, were randomly assigned to independently rate each article in terms of 75 separate methodologic features. Disagreements in ratings were resolved via consensus. Ratings were tabulated separately for eating disorders and anxiety disorders across the three time points. Although there were some differences between anxiety disorders and eating disorders, most of the variables did not substantially differ between these two fields. There was a consistent trend for both fields to show increases in more rigorous methodologies over time. However, both the eating disorder literature and the anxiety disorder literature were characterized by a pervasive absence of many recommended methodologic procedures across the past two decades. Although the eating disorder literature and the anxiety disorder literature are increasingly characterized by improved reporting of rigorous methodologic procedures, there is still a pervasive absence of such procedures in both literatures, which limits the strength of inference in these studies.


Superior colliculus neuronal ensemble activity signals optimal rather than subjective confidence.
Recent studies suggest that neurons in sensorimotor circuits involved in perceptual decision-making also play a role in decision confidence. In these studies, confidence is often considered to be an optimal readout of the probability that a decision is correct. However, the information leading to decision accuracy and the report of confidence often covaried, leaving open the possibility that there are actually two dissociable signal types in the brain: signals that correlate with decision accuracy (optimal confidence) and signals that correlate with subjects' behavioral reports of confidence (subjective confidence). We recorded neuronal activity from a sensorimotor decision area, the superior colliculus (SC) of monkeys, while they performed two different tasks. In our first task, decision accuracy and confidence covaried, as in previous studies. In our second task, we implemented a motion discrimination task with stimuli that were matched for decision accuracy but produced different levels of confidence, as reflected by behavioral reports. We used a multivariate decoder to predict monkeys' choices from neuronal population activity. As in previous studies on perceptual decision-making mechanisms, we found that neuronal decoding performance increased as decision accuracy increased. However, when decision accuracy was matched, performance of the decoder was similar between high and low subjective confidence conditions. These results show that the SC likely signals optimal decision confidence similar to previously reported cortical mechanisms, but is unlikely to play a critical role in subjective confidence. The results also motivate future investigations to determine where in the brain signals related to subjective confidence reside.


Location of M13 coat protein in sodium dodecyl sulfate micelles as determined by NMR.
The major coat protein (gVIIIp) of bacteriophage M13 solubilized in sodium dodecyl sulfate (SDS) detergent micelles was used as a model system to study this protein in the lipid-bound form. In order to probe the position of gVIIIp relative to the SDS micelles, stearate was added, spin-labeled at the 5- or 16-position with a doxyl group containing a stable nitroxide radical. The average position of the spin-labels in the micelles was derived from the line broadening of the resonances in the 13C spectrum of SDS. Subsequently, we derived a model of the relative position of gVIIIp in the SDS micelle from the effect of the spin-labels on the gVIIIp resonances, monitored via 1H-15N HSQC and TOCSY experiments. The results are consistent with the structure of gVIIIp having two helical strands. One strand is a long hydrophobic helix that spans the micelle, and the other is a shorter amphipathic helix on the surface of the micelle. These results are in good agreement with the structure of gVIIIp in membranes proposed by McDonnell et al. on the basis of solid state NMR data [McDonnell, P. A., Shon, K., Kim, Y., & Opella, S. J. (1993) J. Mol. Biol. 233, 447-463]. This study indicates that high-resolution NMR on this membrane protein, solubilized in detergent micelles, is a very suitable technique for mimicking these proteins in their natural environment. Furthermore, the data indicate that the structure of the micelle near the C-terminus of the major coat protein is distorted.(ABSTRACT TRUNCATED AT 250 WORDS)


Influenza vaccination coverage among adults in Korea: 2008-2009 to 2011-2012 seasons.
The aim of this study was to examine seasonal and pandemic influenza vaccination coverage in adults from the 2008-2009 season to the 2011-2012 season, including pandemic and post-pandemic seasons in Korea. We collected data of self-reported vaccine use from the Korean Community Health Survey. We also collected information on socioeconomic status and health behaviors in subpopulations. We tested for linear trends among the data to investigate vaccine coverage before and after the pandemic; and multiple logistic regression analyses were performed to identify predictors of obtaining the influenza vaccination. The results revealed a steady increase in vaccination coverage in every subgroup during four consecutive seasons. The highest rate of vaccine coverage (43.6%) occurred two years after the pandemic. Factors associated with vaccine receipt were: older age; lower education level; lower income; and health behaviors such as regular walking and receiving a health check-up. Smoking and drinking alcohol were inversely associated with vaccination. Having a chronic health condition was also a strong predictor of vaccine receipt. Though vaccination coverage rates were high in high-risk groups; disparities in coverage rates were substantial; particularly in young adults. Interventions are needed to minimize the coverage gaps among subgroups and to improve overall vaccination rates.


Visual constructive and visual-motor skills in deaf native signers.
Visual constructive and visual-motor skills in the deaf population were investigated by comparing performance of deaf native signers (n=20) to that of hearing nonsigners (n=20) on the Beery-Buktenica Developmental Test of Visual-Motor Integration, Rey-Osterrieth Complex Figure Test, Wechsler Memory Scale Visual Reproduction subtest, and Stanford-Binet Intelligence Scale Paper Folding and Cutting subtest. Deaf signers were found to perform similarly to hearing controls, suggesting that these tests are valid assessment instruments to use with deaf individuals.


Chronic total renal artery occlusion: a diagnostic challenge.
Chronic renal artery occlusion must be suspected whenever a moderate hypertensive patient over 50 years of age presents increase of blood pressure refractory to treatment, sometimes causing heart failure or stroke. This suspicion is reinforced by the presence of renal insufficiency and of anatomical and/or functional lateralization of renal damage at intravenous pyelography.


Effect of age at slaughter on carcass traits and meat quality of Italian heavy pigs.
Barrows and gilts (n = 128) from four breed crosses were used to investigate the effect of age at slaughter on carcass traits, proteolytic enzyme activity, and meat and fat quality. Pigs were blocked by breed cross into four blocks, and within blocks, one pen (eight barrows and eight gilts) was assigned randomly to be slaughtered at either 8 or 10 mo of age. Pigs were fed a corn-barley-soybean meal finisher diet from 104 +/- 2.5 d of age (37.7 +/- 0.33 kg BW) to the appropriate slaughter age. Carcasses from older (10 mo) pigs had lower (P < 0.01) muscularity indexes and lean cut yields than those of younger (8 mo) pigs, but dressing percentage and longissimus muscle area increased (P < 0.01) with age. Older pigs produced a redder (P < 0.01) and darker (P < 0.05) semimembranosus, with lower (P < 0.01) ultimate pH and cathepsin B and B + L activities, as well as higher (P < 0.01) aminopeptidase hydrolyzing activity than younger pigs. Moreover, the longissimus muscle of pigs slaughtered at 10 mo of age had lower (P < 0.01) drip and cooking loss percentages than that from pigs slaughtered at 8 mo of age. Ham subcutaneous fat from 10-mo-old pigs had greater (P < 0.05) percentages of oleic acid and lower (P < 0.01) proportions of moisture, linoleic, and linolenic acids than subcutaneous fat from pigs slaughtered at 8 mo of age. Results from this study indicate that fresh hams from pigs slaughtered at 10 mo of age would be more suitable for the production of high-quality, Italian, dry-cured hams.


Binge eating and satiety in bulimia nervosa and binge eating disorder: effects of macronutrient intake.
The current study tested the hypothesis that supplemental dietary protein would reduce binge eating frequency and test meal intake in women with bulimia nervosa (BN) or binge eating disorder (BED). Eighteen women with BN or BED ingested high-carbohydrate or high-protein supplements (280 kcal) three times daily over two 2-week periods. On the morning after each period, participants were given a high-protein or high-carbohydrate supplement (420 kcal) 3 hr before an ad libitum meal. Binge eating episodes occurred less frequently during protein supplementation (1.12 episodes per week) than during carbohydrate supplementation (2.94 episodes per week) or baseline (3.01 episodes per week). Participants reported less hunger and greater fullness, and consumed less food at test meals, after protein than after carbohydrate (673 vs. 856 kcal). Adding protein to the diets of women with BN and BED reduced food intake and binge eating over a 2-week period. These findings may have implications for the longer-term treatment of these disorders.


Btn3 regulates the endosomal sorting function of the yeast Ent3 epsin, an adaptor for SNARE proteins.
Ent3 and Ent5 are yeast epsin N-terminal homology (ENTH) domain-containing proteins involved in protein trafficking between the Golgi and late endosomes. They interact with clathrin, clathrin adaptors at the Golgi (AP-1 and GGA) and different SNAREs (Vti1, Snc1, Pep12 and Syn8) required for vesicular transport at the Golgi and endosomes. To better understand the role of these epsins in membrane trafficking, we performed a protein-protein interaction screen. We identified Btn3 (also known as Tda3), a putative oxidoreductase, as a new partner of both Ent3 and Ent5. Btn3 is a negative regulator of the Batten-disease-linked protein Btn2 involved in the retrieval of specific SNAREs (Vti1, Snc1, Tlg1 and Tlg2) from the late endosome to the Golgi. We show that Btn3 endosomal localization depends on the epsins Ent3 and Ent5. We demonstrated that in btn3Δ mutant cells, endosomal sorting of ubiquitylated cargos and endosomal recycling of the Snc1 SNARE are delayed. We thus propose that Btn3 regulates the sorting function of two adaptors for SNARE proteins, the epsin Ent3 and the Batten-disease-linked protein Btn2.


Periodicity and stability for variable-time impulsive neural networks.
The paper considers a general neural networks model with variable-time impulses. It is shown that each solution of the system intersects with every discontinuous surface exactly once via several new well-proposed assumptions. Moreover, based on the comparison principle, this paper shows that neural networks with variable-time impulse can be reduced to the corresponding neural network with fixed-time impulses under well-selected conditions. Meanwhile, the fixed-time impulsive systems can be regarded as the comparison system of the variable-time impulsive neural networks. Furthermore, a series of sufficient criteria are derived to ensure the existence and global exponential stability of periodic solution of variable-time impulsive neural networks, and to illustrate the same stability properties between variable-time impulsive neural networks and the fixed-time ones. The new criteria are established by applying Schaefer's fixed point theorem combined with the use of inequality technique. Finally, a numerical example is presented to show the effectiveness of the proposed results.


[Two adult cases with corrected transposition of the great arteries treated with permanent endocardial pacemaker implantation].
[Case 1] A 32 year-old male had (I, D, D) type corrected transposition of the great arteries (cTGA) associated with ventricular septal defect and pulmonary stenosis. [Case 2] A 69 year-old male had (S, L, L) type cTGA associated with tricuspid regurgitation. Both cases showed advanced atrioventricular (AV) block due to HV block. Both patients had endocardial DDD pacemakers implanted, with no complication. (I, D, D) type cTGA is rarely accompanied with AV block, while the incidence of AV block is high in (S, L, L) type cTGA. We speculate that this results from the difference in the position of the AV node between these two types.


Formation of tubuloreticular inclusions in human lymphoma cells compared to the induction of 2'-5'-oligoadenylate synthetase by leucocyte interferon in dose-effect and kinetic studies.
Exposure of human lymphoblastoid cell cultures to leukocyte interferon initiated the formation of membranous tubuloreticular inclusions (TRI) within the endoplasmic reticulum or perinuclear envelope. In four different cell lines originating from patients with lymphocytic cancers (Daudi, Raji, H-SB2, and SB), this unique ultrastructural effect displayed a log-linear relationship to increasing doses of interferon-alpha and was dose and time dependent. TRI morphogenesis began within 12 hr in Daudi or Raji cells exposed continuously to 500 IU of leukocyte interferon/ml, but only at 20 hr after 2- to 4-hr pulse exposures to 50 to 100 IU/ml. The TRI accumulation, determined by thin-section counts, reached maximal levels of up to 16% of cell sections within 48 to 72 hr. Experiments with Raji cells indicated a decrease in TRI formation during successive cell divisions; detection of TRI after a pulse of interferon was enhanced when DNA replication was arrested. TRI morphogenesis appeared to be independent of several other known biological actions of interferons. It manifested later than the induction of 2'-5'-oligoadenylate synthetase activity which has been correlated with establishment of the antiviral state and occurred in cell lines, including DaudiKIFNR, which resist the growth-inhibitory effects of leukocyte interferon. Participation of new polypeptide synthesis was indicated by experiments with inhibitors of transcription (actinomycin D) or translation (cycloheximide): TRI morphogenesis was blocked when actinomycin D was added 4 hr after interferon and was reduced when cycloheximide was added for the interval of 13 to 23 hr after interferon.


Hypervalent Iodine(III)-Promoted Phenyl Transfer Reaction from Phenyl Hydrazides to Nitriles.
A useful transformation of nitriles to N-phenyl amides has been achieved through a novel intermolecular phenyl transfer reaction from phenyl hydrazides and N-addition to nitriles in the presence of PIFA under mild and solvent-free conditions. This cross-coupling reaction includes the oxidative cleavage of sp2 C-N bonds of phenyl hydrazides to form a phenyl radical and the subsequent N-addition to cyanos to form new sp2 C-N bonds and provides efficient access to various N-phenyl amides in moderate to good yields under mild reaction conditions.


A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.
In the primate cerebral cortex, morphologically and functionally diverse classes of local circuit neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) differentially regulate the activity of pyramidal cells, the principal type of excitatory output neurons. In schizophrenia, GABA neurotransmission in the prefrontal cortex (PFC) appears to be disturbed but whether specific populations of GABA neurons are affected is not known. The chandelier class of GABA neurons are of particular interest because their axon terminals, which form distinctive arrays termed "cartridges," provide inhibitory input exclusively to the axon initial segment of pyramidal cells. Thus, chandelier cells are positioned to powerfully regulate the excitatory output of pyramidal neurons and, consequently, to substantially affect the patterns of neuronal activity within the PFC. In this study, an antibody directed against the GABA membrane transporter GAT-1 was used to label GABA axon terminals in postmortem human brains. The relative density of GAT-1-immunoreactive axon cartridges furnished by chandelier neurons was decreased by 40% in the PFC of schizophrenic subjects compared with matched groups of normal control and nonschizophrenic psychiatric subjects. In contrast, markers of the axon terminals of other populations of GABA neurons were not altered in the schizophrenic subjects. Furthermore, the density of GAT-1-immunoreactive axon cartridges was not altered in psychiatric subjects who had been treated with antipsychotic medications. The changes in GAT-1-immunoreactive axon cartridges of chandelier neurons in schizophrenia are likely to reflect altered information processing within the PFC and in its output connections to other brain regions and could contribute to the cognitive impairments seen in this disorder.


Ultrasound-guided short-axis out-of-plane vs. long-axis in-plane technique for radial artery catheterization: an updated meta-analysis of randomized controlled trials.
Short-axis out-of-plane (SA-OOP) and long-axis in-plane (LA-IP) are the two major approaches used in ultrasound (US)-guided radial arterial catheterization. Nevertheless, their efficacy and safety remain controversial. Therefore, this meta-analysis aimed at comparing the two approaches for radial arterial catheterization. The PubMed, Embase, and Cochrane Library databases were searched for relevant articles published from database inception until December 2020. We selected randomized controlled trials comparing the short- and long-axis methods for US-guided radial artery catheterization. The results were analyzed using RevMan software to determine the adequacy and conclusiveness of the available evidence. Six studies (725 patients) ultimately met the inclusion criteria. No significant difference was observed between the SA-OOP and LA-IP approaches for US-guided radial artery catheterization (relative risk [RR], 0.99; 95% confidence interval [CI], 0.96-1.03; p =0.61; I2=0%). The first-attempt success rate was similar between the two groups (relative risk [RR], 1.02; 95% CI, 0.79-1.32; p =0.90; I2=87%). The incidence of hematoma formation was similar between the two groups (RR, 1.91; 95% CI, 0.66-5.56; p =0.24; I2=77%). The SA-OOP approach does not increase the total or first-attempt success rate of radial artery catheterization using the LA-IP approach. More highly powered well-designed trials are needed to evaluate additional outcomes.


NO-Donor Nitrosyl Iron Complex with 2-Aminophenolyl Ligand Induces Apoptosis and Inhibits NF-κB Function in HeLa Cells.
NO donating iron nitrosyl complex with 2-aminothiophenyl ligand (2-AmPh complex) was studied for its ability to cause cell death and affect nuclear factor kappa B (NF-κB) signaling. The complex inhibited viability of HeLa cells and induced cell death that was accompanied by loss of mitochondrial membrane potential and characteristic for apoptosis phosphatidylserine externalization. At IC50, 2-AmPh caused decrease in nuclear content of NF-κB p65 polypeptide and mRNA expression of NF-κB target genes encoding interleukin-8 and anti-apoptotic protein BIRC3. mRNA levels of interleukin-6 and anti-apoptotic protein BIRC2 encoding genes were not affected. Our data demonstrate that NO donating iron nitrosyl complex 2-AmPh can inhibit tumor cell viability and induce apoptosis that is preceded by impairment of NF-κB function and suppression of a subset of NF-κB target genes.


Supporting-emotional needs of Iranian parents with premature infants admitted to Neonatal Intensive Care Units.
Having an infant in the neonatal intensive care unit (NICU) is a stressful and painful experience. Unlike to normal births, this birth is associated with admission and separation of infant from parents. The aim of this study was to compile the supporting-emotional needs of Iranian parents who have a premature infant admitted in (NICU). This study was performed using qualitative research approach. Twelve participants including 9 parents whose infant had been hospitalized in NICU; two nurses and one physician were also selected for sampling purposes. Data were gathered using semi-structured interview. Data were analyzed by inductive content analysis approach. Four subcategories emerged from data analysis expressed supporting-emotional needs of parents of premature infants admitted in NICU. These subcategories were: Need for interaction with infant, Need to medical team's empathy, need to exchange support with spouse, and Need to get help from others. In order to develop mutual bonding with infant and attain parental roles, parents need to be close their neonate, also receive empathy and support to find a way to meet their needs. Participants in this study announced that resolving these needs can help parents to feel more confidence in infant's care and reduce their negative feelings.


Interactions between domperidone and ropinirole, a novel dopamine D2-receptor agonist.
1. Ropinirole, SK&F 101468 has been characterized preclinically as a specific dopamine D2-receptor agonist. Nine male healthy subjects were investigated for the effects on supine and erect heart rate and blood pressure, catecholamines and prolactin, of a single dose of 800 micrograms ropinirole preceded by a single dose of 20 mg domperidone or domperidone-placebo, and those of a single dose of domperidone followed by ropinirole-placebo. 2. Single doses of 800 micrograms ropinirole did not cause clinically significant changes in supine resting heart rate and blood pressure. However, they caused postural faintness on 3 min immobile upright standing on 10/26 occasions. 3. Pretreatment with 20 mg domperidone 1 h before administration of ropinirole prevented the postural symptoms in all but one subject. It did not alter ropinirole's plasma pharmacokinetics. 4. Ropinirole did not alter supine or standing catecholamine concentrations. 5. Domperidone increased the plasma concentrations of prolactin whereas ropinirole administered alone reduced them. A single dose of 800 micrograms ropinirole did not attenuate the prolactin increase induced by a single dose of 20 mg domperidone administered 1 h earlier.


The effects of melatonin on ischemia-reperfusion induced changes in rat corpus cavernosum.
We determined the change in contractile activity and oxidant damage after ischemia-reperfusion of rat corpus cavernosum and investigated the effects of melatonin (Sigma Chemical Co., St. Louis, Missouri) on these parameters. The abdominal aorta of male Wistar albino rats was occluded to induce ischemia-reperfusion. Melatonin (10 mg./kg.) or vehicle (1% alcohol in saline per kg.) was administered subcutaneously before ischemia-reperfusion. In the sham operated control group the abdominal aorta was left intact and the rats were treated with melatonin or vehicle. After decapitation corporeal tissues were placed in organ baths or stored for biochemical measurements. In sham operated rats phenylephrine added cumulatively caused a concentration dependent contraction in corpus cavernosum strips precontracted with KCl and acetylcholine added cumulatively to strips precontracted with phenylephrine caused a dose dependent relaxation response. In the ischemia-reperfusion group contraction and relaxation responses decreased significantly compared within controls. Melatonin treatment in the ischemia-reperfusion group reversed these responses. Myeloperoxidase activity and the lipid peroxidation level of the corporeal tissues in the ischemia-reperfusion group were significantly higher than in the sham operated control group. Melatonin treatment in the ischemia-reperfusion group decreased myeloperoxidase activity and the lipid peroxidation level compared with ischemia-reperfusion alone, whereas melatonin treatment alone had no significant effect on these parameters. In this study the corporeal tissues of rats exposed to ischemia-reperfusion had lower responses to contractile and relaxant agents than those of sham operated rats. Treatment with melatonin before ischemia-reperfusion almost completely reversed smooth muscle responses and prevented the increased myeloperoxidase activity and lipid peroxidation of corporeal tissues.


Structures and dynamics of β-barrel oligomer intermediates of amyloid-beta16-22 aggregation.
Accumulating evidence suggests that soluble oligomers are more toxic than final fibrils of amyloid aggregations. Among the mixture of inter-converting intermediates with continuous distribution of sizes and secondary structures, oligomers in the β-barrel conformation - a common class of protein folds with a closed β-sheet - have been postulated as the toxic species with well-defined three-dimensional structures to perform pathological functions. A common mechanism for amyloid toxicity, therefore, implies that all amyloid peptides should be able to form β-barrel oligomers as the aggregation intermediates. Here, we applied all-atom discrete molecular dynamics (DMD) simulations to evaluate the formation of β-barrel oligomers and characterize their structures and dynamics in the aggregation of a seven-residue amyloid peptide, corresponding to the amyloid core of amyloid-β with a sequence of 16KLVFFAE22 (Aβ16-22). We carried out aggregation simulations with various numbers of peptides to study the size dependence of aggregation dynamics and assembly structures. Consistent with previous computational studies, we observed the formation of β-barrel oligomers in all-atom DMD simulations. Using a network-based approach to automatically identify β-barrel conformations, we systematically characterized β-barrels of various sizes. Our simulations revealed the conformational inter-conversion between β-barrels and double-layer β-sheets due to increased structural strains upon forming a closed β-barrel while maximizing backbone hydrogen bonds. The potential of mean force analysis further characterized the free energy barriers between these two states. The obtained structural and dynamic insights of β-barrel oligomers may help better understand the molecular mechanism of oligomer toxicities and design novel therapeutics targeting the toxic β-barrel oligomers. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.


Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.
Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi's sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identify specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.


Differentiating neoplasms of hair germ.
Differentiating neoplasms of hair germ are benign epithelial-mesenchymal tumours of skin in which hair follicle development may be partly or completely recapitulated. The epithelial component is equivalent to the hair germ. The mesenchymal component is equivalent to the dermal papilla. Epithelial-mesenchymal interaction results in the morphogenesis of hair follicles. In neoplasms showing stromal induction, there is centrifugal organizations: hair bulbs are found at the periphery of tumour lobules and hairs are projected centrally to lie within small keratinizing cysts. Neoplasms of hair germ without advanced morpho-differentiation are termed ;trichoblastomas', and those neoplasms in which hair follicle development is advanced are called ;trichogenic trichoblastomas'.


Evidence for both respiratory syncytial virus and measles virus antigens in the osteoclasts of patients with Paget's disease of bone.
Recent ultrastructural and immunohistochemical evidence supports the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family. Conflicting evidence for the presence of respiratory syncytial virus (RSV), a pneumovirus, or measles, a morbillivirus, has been reported. By the indirect fluorescent antibody assay, four RSV antisera were compared with four measles antisera on serial sections of pagetic bone or replicate coverslips of cells from pagetic bone grown in culture from 30 patients. Results produced positive immunofluorescence for RSV in 28 of 29 patients and positive immunofluorescence for measles in 11 of 22 patients. Of the 20 patients from whom comparable samples could be tested for antigens, 11 were found to harbor both antigens. These studies support the hypothesis that Paget's disease of bone is a slow viral infection of the Paramyxoviridae family more closely related to the pneumoviruses than the morbilliviruses.


[A comparison of complete and incomplete antibodies by Middlebrook-Dubos, Boyden and Coombs hemagglutination tests in man].
The antibodies in the sera of 160 tuberculous persons and in a control group of 100 healthy persons were investigated by Middlebrook-Dubos (M-D), Boyden hemagglutination and modified M-D antiglobulin methods. By the M-D method 88% of the sera from 135 persons with lung tuberculosis, and 57.1% sera from 21 persons with other organ tuberculosis gave positive results. In the control group of 100 persons 11% were positive, while all of PPD negative persons remained negative. By Boyden method 90% of 135 lung tuberculosis, 57.1% of 21 with other organ tuberculosis and 4% of the control group gave positive results. In 91.2% of 80 persons with lung tuberculosis, tested with modified M-D antiglobulin method, found incomplete antibodies. The difference in control groups (11%, 4%), and in persons with active tuberculosis (88%, 90%) indicates that the serological tests are just as significant as other diagnostic methods.


[A documental investigation of Hakodate Medical School from records of a student].
At Hakodate National General Hospital, a medical course (Hakodate Medical School) existed from 1872 to 1874 with governmental support, which was guided and lectured by Dr. Stuart Erdridge from Philadelphia. From many records concerning this course written by a student who attended during this period, real features of this course were clarified. Dr. S. Erdridge gave lectures in English about the fundamental as well as clinical aspects of medicine, including surgery, and gave guidance on clinical practise and treatments. These lectures were translated into Japanese simultaneously by an interpreter for the convenience of students writing in Japanese in their notebooks. His lectures were on a high level for that time, so later they were published in 3 volumes by the government (Kaitakushi). The nine of those 20 students who were supported by government expense were obligated to do medical services in Hokkaido for 5 years afterward. At the end of the course, students who took the course were engaged for 50 days in medical service which included a round trip for vaccination of small pox to children living near the Hakodate area and 2558 children were vaccinated. From the diary of this trip, the schedule and mode of vaccination at that time were clarified. The student who wrote this diary had to retire from this course at the last period, due to the death of his father and familial duties. However, the certificate for medical occupation was issued to him by Dr. S. Erdridge in 1886 for governmental necessity.


[Treponema pallidum or Spirochaeta pallida?].
First Schaudinn and Hoffmann named the causative organism of syphilis Spirochaeta pallida. Short time later Schaudinn proposed the name Treponema. He mentioned it in a letter of October 14, 1905 to Hoffmann. He supposed that this germ may be a flagellate. This was not correct. The electron-microscopic investigations revealed that this idea did not concur. Therefore it is better to call them Spirochaeta pallida and not Treponema pallidum any more.


DNA Nanobots - Emerging Customized Nanomedicine in Oncology.
Cancer is one of the most lethal diseases of the twenty-first century. Many medicines, including antitumor antibiotics, deliver tedious and severe chemotherapy and radiation treatment, both of which have significant side effects. DNA nanorobots, as an alternative, might be used as a cancer treatment method that is both safer and more precise than current treatments. DNA nanobots are being praised as a major milestone in medical research. The major goal of these nanobots is to find and destroy malignant cells in the human body. A unique strand of DNA is folded into the systematic form to create these nanobots. DNA origami has magnified passive tumor-targeting and prolonged properties at the tumor location. The triangle-like DNA origami, in particular, shows excellent accumulation on passive targeting of the tumor. Self-built DNA origami nanostructures were utilized to deliver the anticancer drug doxorubicin into tumors, and the approach was found to be highly successful in vivo. In another demonstration, a robot was made with the help of DNA origami and aptamer for folding a 90nm long tube-like apparatus. It was carried out to transport the blood coagulation protease thrombin in the interior portion guarded against blood plasma protein and circulating platelets. The robot unfolded once the aptamer was identified and attached to its tumor-specific target molecule, delivering thrombin to the circulation, stimulating coagulation of the regional malignant cells, and proceeding to tumor necrosis and tumor growth inhibition. Various studies revealed the effectiveness of DNA nanobots in cancer therapy.


The Agr communication system provides a benefit to the populations of Listeria monocytogenes in soil.
In this study, we investigated whether the Agr communication system of the pathogenic bacterium Listeria monocytogenes was involved in adaptation and competitiveness in soil. Alteration of the ability to communicate, either by deletion of the gene coding the response regulator AgrA (response-negative mutant) or the signal pro-peptide AgrD (signal-negative mutant), did not affect population dynamics in soil that had been sterilized but survival was altered in biotic soil suggesting that the Agr system of L. monocytogenes was involved to face the complex soil biotic environment. This was confirmed by a set of co-incubation experiments. The fitness of the response-negative mutant was lower either in the presence or absence of the parental strain but the fitness of the signal-negative mutant depended on the strain with which it was co-incubated. The survival of the signal-negative mutant was higher when co-cultured with the parental strain than when co-cultured with the response-negative mutant. These results showed that the ability to respond to Agr communication provided a benefit to listerial cells to compete. These results might also indicate that in soil, the Agr system controls private goods rather than public goods.


Optimization and production of curdlan gum using Bacillus cereus PR3 isolated from rhizosphere of leguminous plant.
Curdlan gum is a neutral water-insoluble bacterial exopolysaccharide composed primarily of linear β-(1,3) glycosidic linkages. Recently, there has been increasing interest in the applications of curdlan and its derivatives. Curdlan is found to inhibit tumors and its sulfated derivative possess anti-HIV activity. Curdlan is biodegradable, non-toxic towards human, environment and edible which makes it suitable as drug-delivery vehicles for sustained drug release. The increasing demand for the growing applications of curdlan requires an efficient high yield fermentation production process so as to satisfy the industrial needs. In this perspective, the present work is aimed to screen and isolate an efficient curdlan gum producing bacteria from rhizosphere of ground nut plant using aniline-blue agar. High yielding isolate was selected based on curdlan yield and identified as Bacillus cereus using gas-chromatography fatty acid methyl ester analysis. B. cereus PR3 curdlan gum was characterized using FT-IR spectroscopy, SEM, XRD and TGA. Fermentation time for curdlan production using B. cereus PR3 was optimized. Media constituents like carbon, nitrogen and mineral sources were screened using Plackett-Burman design. Subsequent statistical analysis revealed that Starch, NH4NO3, K2HPO4, Na2SO4, KH2SO4 and CaCl2 were significant media constituents and these concentrations were optimized for enhancement of curdlan production up to 20.88 g/l.


CREDO: a structural interactomics database for drug discovery.
CREDO is a unique relational database storing all pairwise atomic interactions of inter- as well as intra-molecular contacts between small molecules and macromolecules found in experimentally determined structures from the Protein Data Bank. These interactions are integrated with further chemical and biological data. The database implements useful data structures and algorithms such as cheminformatics routines to create a comprehensive analysis platform for drug discovery. The database can be accessed through a web-based interface, downloads of data sets and web services at http://www-cryst.bioc.cam.ac.uk/credo. Database URL: http://www-cryst.bioc.cam.ac.uk/credo.


How physicians can help their patients quit smoking. A practical guide.
We describe practical, effective, office-based methods for physicians to use to assist patients to stop smoking that do not require special training or support personnel. Brief counseling achieves smoking cessation in a small percent of well patients but is more effective in patients with smoking-related illnesses or abnormal laboratory test results. Routine prescribing of nicotine gum without participation by the patient in a smoking-cessation program does not increase smoking cessation, and we do not recommend it. The prevention of smoking relapse can probably be enhanced by scheduling follow-up office visits after the patient has quit. Failure to quit on initial attempts should not discourage physicians and patients, since most successful abstainers usually must make several attempts to quit. We outline for physicians two approaches, one brief and one more intensive, to help patients stop smoking.


Anomalous origin of the left coronary artery from the pulmonary trunk: its clinical spectrum and current surgical management.
An anomalous left coronary artery arising from the pulmonary artery is a rare congenital anomaly which carries a serious prognosis with a high mortality in infants. Our experience in the surgical treatment of 9 patients with this condition during the last 5 years is discussed. The majority of patients were under the age of 2 years and presented with left ventricular failure. Surgical procedures included simple ligation of the left coronary artery, left subclavian to left coronary artery anastomosis, interposition vein graft, and direct reimplantation of the left coronary artery into the aorta. Patients treated by simple ligation survived the procedure but did not show improvement. Results with the subclavian artery to left coronary artery anastomosis were disappointing. Direct reimplantation or interposition of a saphenous vein graft appears to be the method of choice.


Guidelines for graduate medical education in geriatrics.
There has been a substantial increase in training programs in geriatrics over the past several years. In this paper the authors propose guidelines for geriatric training at the graduate medical educational level, both for specialized training (geriatric fellowship) and training in geriatrics as part of other specialty training (internal medicine, family practice, psychiatry, and neurology). Experts from relevant specialty boards and societies, an advisory group in geriatrics, and the faculty of the University of California-Los Angeles Multicampus Division of Geriatrics participated in a modified Delphi study which provided the information used to formulate the guidelines. Performance objectives, core content, training experiences, and clinical exposure and program evaluations are described for geriatric fellows and house staff members in internal medicine, family practice, neurology, and psychiatry. Recommendations included here may be of use to deans, faculty members, and educators responsible for the development of the many new geriatric training programs.


Selective effects of ECT on hypothalamic-pituitary activity.
The hypothesis that ECT produces selective effects on hypothalamic-pituitary activity was investigated by determining the effect of ECT on pituitary hormone release in nine depressed patients. After ECT there were massive and rapid increases in the plasma concentrations of nicotine- and oestrogen-stimulated neurophysin (NSN and ESN), prolactin (PRL) and adrenocorticotropin (ACTH), smaller increases in plasma luteinizing hormone (LH) and cortisol, a significant decrease in plasma growth hormone (GH) concentration but no change in plasma thyrotropin (TSH). There was significant attenuation of PRL responses with repeated ECT. The hormonal responses to ECT cannot simply be attributed to stress, since a similar pattern of increases in plasma hormone concentrations did not occur in psychologically normal patients in whom plasma hormone concentrations were measured during induction of anaesthesia and abdominal incision for cholecystectomy. Analysis of these hormonal responses in terms of the knowledge available on the neurotransmitter control of pituitary hormone release suggests that some of these hormonal responses to ECT may be mediated by the activation of serotonergic neurones, while others are probably due to direct stimulation of the neuroendocrine neurones themselves.


Axon initial segment dysfunction in epilepsy.
The axon initial segment (AIS) contains the site of action potential initiation and plays a major role in neuronal excitability. AIS function relies on high concentrations of different ion channels and complex regulatory mechanisms that orchestrate molecular microarchitecture. We review recent evidence that a large number of ion channels associated with epilepsy are enriched at the AIS, making it a 'hotspot' for epileptogenesis. Furthermore, we present novel data on the clustering of GABRgamma2 receptors in the AIS of cortical and hippocampal neurons in a knock in mouse model of a human genetic epilepsy. This article highlights the molecular coincidence of epilepsy mutations at the AIS and reviews pathogenic mechanisms converging at the AIS.


Bilateral macular cyst after lightning visualized with optical coherence tomography.
The authors report a 14-year-old girl who was struck by lightning with bilateral macular cyst that was diagnosed with optical coherence tomography (OCT). Her fundus examination revealed bilateral macular lesions that simulated macular holes. The Watzke-Allen sign was negative in the right eye and positive in the left eye. Fluorescein angiography showed a foveal window defect in both eyes. OCT demonstrated a small foveal cyst evident as a hyporeflective lucency, visible just anterior to the retinal pigment epithelium/choriocapillaris complex in both eyes. OCT seems to be useful in the evaluation of lighting maculopathy to rule-out full-thickness macular hole in these cases, and avoid unnecessary surgery.


Serum IL-5 and IFN-γ Are Novel Predictive Biomarkers for Anti-PD-1 Treatment in NSCLC and GC Patients.
Because responses of patients with cancer to immunotherapy can vary in success, effective biomarkers are urgently needed for predicting clinical response with anti-PD-1 treatment. We aimed to evaluate the IL-5 and IFN-γ level with the response of anti-PD-1 blockade in non-small-cell lung cancer (NSCLC) and gastric cancer (GC). Metastatic NSCLC and GC patients treated with anti-PD-1 monoclonal antibody were studied. Blood samples were taken before PD-1 McAb treatment, after the first cycle treatment, and during efficacy evaluation. The association between IL-5 and IFN-γ levels and clinical response were analyzed by the nonparametric Wilcoxon matched-pairs ranked tests. The progression-free survival (PFS) time was obtained by imaging evaluation and telephone follow-up of all the patients. Kaplan-Meier and the log rank test were used to plot the survival curve. IL-5 and IFN-γ levels were detected in the peripheral blood of 40 NSCLC and 35 GC patients who have received anti-PD-1 treatment. In effective group, IL-5 and IFN-γ levels at best response points significantly decreased (P < 0.001) compared with pretherapeutic levels in NSCLC and GC patients with lymph node or distant metastasis. Compared with pretherapeutic levels, IL-5 and IFN-γ levels largely increased as the tumor progresses (P < 0.01). Higher IL-5 and IFN-γ levels before treatment indicated shorter progression-free survival in patients with NSCLC metastasis (P = 0.007, P = 0.0111). Moreover, their levels also accurately reflected the pseudoprogression of two NSCLC patients to anti-PD-1 treatment. Our results suggested that serum IL-5 and IFN-γ levels could be an effective indicator for predicting clinical efficacy and survival with anti-PD-1 blockade in NSCLC and GC patients.


The impact of partial hepatectomy on oxidative state in the liver remnant - An in vivo swine model.
Previous studies on oxidative state after partial hepatectomy (PHx) report conflicting data on levels of glutathione (GSH) and are mainly presented in rodent models by methodology less sensitive than the present technologies. The current swine model presents GSH levels and the following genetic response post-PHx, utilizing an analytical platform more sensitive and precise than earlier available. Twelve pigs were randomized to a PHx- and a control group (n=6 in each). The PHx group had a 60% hepatectomy. Serial in vivo liver biopsies during 12h of anaesthesia post-PHx were analyzed for GSH by liquid chromatography mass spectrometry (LC-MS/MS). Transcriptional alterations of genes (GS, GCLM, GCLC, GR, HGF, NFE2L2, TGFβ1) regulating GSH synthesis were measured by real-time PCR. No difference was detected between the GSH levels in the PHx- and the control group during the experiment (P=0.247). Still, decreased gene expression of GS (P=0.026) and NFE2L2 (P=0.014) the first nine hours, and a decrease of TGFβ1 (P=0.029) the first seven hours post-PHx was seen in the liver remnant. The results show that the liver has an extended capacity to maintain GSH homeostasis during major stress and parenchymal loss, even at the early onset of such trauma. This observation was not explained by increased expression of key genes in GSH pathways. Consequently, the results indicate an inherent compensatory capacity to maintain GSH homeostasis in the reduced organ.


The effects of familial relationships, age, body weight, and diet on blood pressure and the 24 hour urinary excretion of sodium, potassium, and creatinine in men, women, and children of randomly selected families.
Two hundred thirty-three randomly selected families provided a population for studying the effects of familial relationships, age, diet, body weight, and urinary electrolyte excretion on blood pressure. There was a strong familial component for urinary sodium, potassium, and creatinine excretion and for systolic blood pressure. In individuals, age, heart rate, and body weight were independently related to blood pressure. In women, urinary sodium and potassium levels were related to diastolic blood pressure. These individual relationships persisted when age was accounted for but were no longer significant after adjusting for both age and body weight, suggesting that heavier people eat more food, which in our culture means greater sodium intake. In fact, our randomly selected families were eating as much sodium (130 to 170 meq/day) and as little potassium (50 to 70 meq/day) as consumed by Americans several decades ago. Furthermore, this study again documented the rise in blood pressure with age, which may represent the effect of environmental influences on blood pressure over time. The familial aggregation of urinary sodium, potassium, and creatinine excretion, along with the well-established familial aggregation of body weight, emphasizes the importance of the entire family in the treatment and prevention of hypertension.


Repeated injections of piracetam improve spatial learning and increase the stimulation of inositol phospholipid hydrolysis by excitatory amino acids in aged rats.
Repeated injections of piracetam (400 mg/kg, i.p. once a day for 15 days) to 16-month old rats led to an improved performance on an 8-arm radial maze, used as a test for spatial learning. This effect was accompanied by a greater ability of excitatory amino acids (ibotenate and glutamate) to stimulate [3H]inositol-monophosphate formation in hippocampal slices incubated in the presence of 10 mM Li+. Repeated administration of piracetam did not induce changes in excitatory amino acid-stimulated polyphosphoinositide hydrolysis in hippocampal slices prepared from 2-month old animals.


Requirement of S-adenosyl-L-methionine-mediated methylation for human monocyte chemotaxis.
The chemotactic response of motile bacteria requires the methylation of specific proteins by S-adenosyl-L-methionine. To determine whether methylation is required for the chemotaxis of human leukocytes, we studied the effects of inhibition of S-adenosyl-L-methionine-mediated methylation on monocyte chemotactic responsiveness. Methylation was inhibited in monocytes by treating the cells with substances that produced elevations in intracellular S-adenosyl-L-homocysteine, a competitive inhibitor of S-adenosyl-L-methionine methylation. Treatment of isolated monocytes with the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, plus exogenous adenosine and L-homocysteine thiolactone increased intracellular S-adenosyl-L-homocysteine levels by as much as 1500-fold. Concomitant with increases in S-adenosyl-L-homocysteine were a decrease in monocyte protein carboxy-O-methylation as well as a marked inhibition of monocyte chemotactic responsiveness. Conditions that almost completely inhibited methylation and chemotaxis did not depress monocyte phagocytosis, indicating that this latter function either is independent of S-adenosyl-L-methionine-mediated methylation or is extremely resistant to inhibition of such reactions by S-adenosyl-L-homocysteine. These studies indicate that S-adenosyl-L-methionine-mediated methylation is required for the chemotaxis of eukaryotic cells and that the chemotactic and phagocytic functions of human monocytes have different requirements for methylation.


Obese strain (OS) chickens with spontaneous autoimmune thyroiditis have a deficiency in thymic nurse cells.
Chicken thymic nurse cells (TNC) were isolated and their plasma membrane antigens were characterized by immunofluorescence with a panel of allo-, hetero-, and monoclonal antibodies. Analogous to the murine system, chicken TNC are localized in the subcapsular region of the cortex and were strongly B-L and B-F positive (MHC Ia and H-2 D, K equivalents). The TNC were non-phagocytic and lacked fc receptors, but expressed an antigen specific for thymic epithelial cells, and their cytoplasm was stained by an anti-keratin antiserum. The internalized lymphocytes were all intact T cells of a distinct differentiation stage, their antigenic profile consistent with that of immature cortical thymocytes. To determine whether TNC may play a role in the activation of autoimmune disease, Obese strain chickens with spontaneous autoimmune thyroiditis were investigated. These chickens were found to have a twofold defect in their TNC content: the thymuses contained approximately one-half of the number of TNC found in normal chickens beginning as early as 17 days of embryogenesis, and the lymphocyte content of the Obese strain TNC was one-half that of the normals. The deficiency is specific for TNC and may be a major reason for the abnormal T cell differentiation in the Obese strain.


[The resection of the head of the pancreas with longitudinal pancreatojejunostomy (Frey procedure)].
The indications to Frey operation are severe pain syndrome and pancreatic hypertension, caused by concrements and strictures of the main pancreatic duct and/or postnecrotic pancreatic cysts. The pancreaticojejunoanastomosis is performed on the isolated by Roux intestinal loop. The average operating time was 4.62±1.39 hours. 28,3% of the operated patients developed various postoperative complications. 2 (6.7%) patients had the anastomosis insufficiency; the 2 patients had intraanastomotic bleeding and 1 patient had the arrosive bleeding caused by pancreonecrosis. 2 patients had external pancreatic fistulae. 1 patient died. The average hospital stay after the operation was 12±4 days.


Toward Parsimony in Bias Research: A Proposed Common Framework of Belief-Consistent Information Processing for a Set of Biases.
One of the essential insights from psychological research is that people's information processing is often biased. By now, a number of different biases have been identified and empirically demonstrated. Unfortunately, however, these biases have often been examined in separate lines of research, thereby precluding the recognition of shared principles. Here we argue that several-so far mostly unrelated-biases (e.g., bias blind spot, hostile media bias, egocentric/ethnocentric bias, outcome bias) can be traced back to the combination of a fundamental prior belief and humans' tendency toward belief-consistent information processing. What varies between different biases is essentially the specific belief that guides information processing. More importantly, we propose that different biases even share the same underlying belief and differ only in the specific outcome of information processing that is assessed (i.e., the dependent variable), thus tapping into different manifestations of the same latent information processing. In other words, we propose for discussion a model that suffices to explain several different biases. We thereby suggest a more parsimonious approach compared with current theoretical explanations of these biases. We also generate novel hypotheses that follow directly from the integrative nature of our perspective.


Role of bacteria in the pathogenesis of short bowel syndrome-associated D-lactic acidemia.
Previously, we have demonstrated that short bowel syndrome (SBS) patients suffer daily from D-lactic acidemia; in these patients rather high amounts of (bacterial) D-lactate emerge in blood and urine with a circadian rhythm. The aim of this study was to establish the microbial basis of D-lactic acidemia in SBS. Therefore, faecal flora of (young and adult) SBS-patients was analysed qualitatively and quantitatively, and compared to that of controls. The isolated bacterial species were screened for massive D- and/or L-lactate production after in vitro growth. After introduction of oral feeding in SBS-infants shortly after the resection, lactobacilli increased from < or = 1% up to 60 +/- 5% of the faecal flora within 2-3 weeks. In the faeces of patients with oral feeding the lactate producers Lactobacillus acidophilus and Lactobacillus fermentum were the major resident bacteria (each with 10(10)-10(12) cfu/g faeces). During active growth in vitro these lactobacilli produced massive amounts of D- and L-lactic acid from glucose. Use of oral antibiotics in two SBS-children did not reduce the total numbers of lactobacilli, but caused shifts within the intestinal populations of at least lactobacilli. It is concluded that the strongly reduced intestinal capacity for carbohydrate absorption and the oral consumption of easily fermentable carbohydrates form the physiological basis for D-lactic acidemia in SBS, and that the fermentative D-lactate production by intestinal bacteria, especially the abundant, resident lactobacilli, forms its microbial basis. In these patients the antimicrobial and therapeutic effects of antibiotics are unpredictable.


Expression and function of gamma delta- and alpha beta-T cell receptor heterodimers on human somatic T cell hybrids.
T cell somatic hybrids were obtained by fusion of human tetanus toxoid-specific gamma + delta + T cells and a T cell lymphoma cell line that expresses beta-chain but not alpha-chain transcripts. The hybrids simultaneously and independently expressed alpha beta and gamma delta TCR heterodimers on the cell surface without any significant differences in the level of expression. No heterodimers containing alpha delta-, beta delta-, beta gamma-, and alpha gamma-chains were transported to the cell membrane, indicating a chain specificity in dimer formation. The presence of productively rearranged gamma- and delta-alleles in the hybrid cells and immunoprecipitation of an identical type of TCR-gamma delta from both hybrid and parental gamma + delta + T cells suggests that TCR-gamma delta on the hybrid cells derives from gamma + delta + T cells. Anti-TCR (TCS-delta 1 or WT31) and anti-CD3 antibodies induced a rapid increase in [Ca2+]i in the double-positive hybrids and their variants positive for either the alpha beta or gamma delta complex. Double positive hybrid cells were refractory to stimulation with anti-CD3 antibody after pretreatment with a mixture of anti-TCR-gamma delta and anti-TCR-alpha beta antibodies but not with either antibody alone indicating the functional independence of the two receptors. However, only gamma delta heterodimer receptor was able to respond to tetanus toxoid presented on autologous APC as measured by induction of the p55 chain of IL-2R on stimulated cells.


Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints in which systemic overproduction of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) may accelerate cardiovascular (CV) complications. Synovial inflammation in RA spreads systemically and transforms silently into chronic inflammation manifested by increased cytokine release and abnormally high levels of acute reactive proteins (ARPs) such as C-reactive protein (CRP), suggesting inflammation as a connecting link between RA and CV dysfunction. While the treatment to improve CV function in RA patients is being validated, it is timely to propose and test two-pronged therapies that ameliorate arthritis concomitant to improving CV functions. In this review, we summarized the pre-clinical and clinical studies validating the cardiovascular and anti-rheumatic activities of epigallocatechin-3 gallate (EGCG), a potent anti-inflammatory molecule found in green tea. The review also draws many parallels that have emerged between the paradigm of cytokine-driven inflammation in the pathogenesis of RA and its CV complications. Finally, based on extensive clinical evidence of the 'synovial inflammation-systemic inflammation' link and the benefits of EGCG in regulating these two pathologies via common driving factors, authors put forward an argument that EGCG may be tested for its potential CV benefit along with anti-rheumatic activity in animal models of human RA.


AAV9-mediated engineering of autotransplanted kidney of non-human primates.
Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the AAV9 capsid in 16 non-human primate tested sera. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an autotransplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. Results in non-human primates represent a step forward in maintaining the portability of this strategy into clinics.


Free-energy landscapes of proteins in the presence and absence of force.
The equilibrium properties of the fourth immunoglobulin domain of filamin from Dictyostelium discoideum (ddFLN4) in the absence and presence of a small force (0-6 pN) pulling the termini apart is characterized through atomistic numerical simulation. The equilibrium free-energy landscape of ddFLN4 is found to change in a complex fashion that cannot be described in terms of one-dimensional projections as usually done in the interpretation of mechanical (un)folding experiments. Nonequilibrium unfolding simulations reveal that the major unfolding intermediate corresponds to a marginally populated state at equilibrium that only appears when a force larger than 4 pN is applied. Finally, we show that if the free-energy difference between states is taken to be linear in the applied force, the proportionality coefficient is not the difference in the end-to-end distance between pair of states as generally assumed even though the data can be reasonably fitted. The present results suggest that mechanical unfolding experiments may reveal states that are not accessible in the absence of force. Thus, special care should be taken when trying to interpret both equilibrium and nonequilibrium mechanical (un)folding experiments in light of the (un)folding properties in the absence of a force.


Barbiturate anticonvulsants in refractory affective disorders.
Despite an increasing literature demonstrating both acute and long-term positive psychopharmacological effects of both valproate and carbamazepine, phenytoin has remained a controversial intervention, and barbiturate anticonvulsants have generally received poor press with regard to psychotropic effects. In the present investigation, 27 seizure-free, affectively ill patients who received therapeutic trials of primidone and/or mephobarbital after failing on antidepressants, lithium, carbamazepine, valproate, and phenytoin were analyzed with regard to effects on illness severity and affective cycle rate over a period of as long as four years. Nine (33%) of the patients had a sustained positive therapeutic effect on affective state and/or psychotic symptoms to primidone and three (11%) had positive effects on mephobarbital after primidone failure. Four (15%) had brief positive effects that were not sustained, and the remaining 11 (41%) had no effects or negative effects to these agents. The theoretical and practical implications of this new and unexpected finding are discussed.


Can propofol precipitate pancreatitis in patients with Cushing's syndrome?
We encountered two cases of acute pancreatitis in patients with Cushing's disease following transnasal transsphenoidal hypophysectomy. In both cases propofol was used in bolus doses, and is thought to be the probable factor for its development. Since elevated cortisol levels in Cushing's disease poses a threat for pancreatitis, there is a possibility that patients with Cushing's disease might be more prone to acute pancreatitis following propofol administration. Anaesthesiologists and physicians dealing with the management of Cushing's disease need to be aware of this possibility.


Long-term improvement in coping skills following multimodal treatment in war veterans with chronic PTSD.
Due to the long-lasting and resistant symptoms characteristic of chronic combat posttraumatic stress disorder (PTSD), its treatment is complex and often requires a tailored therapeutic approach incorporating both psychotherapy and pharmacotherapy. A multimodal approach of psychoeducative, sociotherapeutic, and dynamically oriented trauma-focused groups is described. We assessed the short- and long-term effectiveness of this therapeutic program by monitoring its impact on PTSD symptoms, depression, neurotic symptoms, coping skills, and quality of life for three years. The findings revealed short-term reduction in the symptoms of PTSD and depression, while the long-term results were manifested as the increased use of all coping mechanisms and a greater level of obsession.


Quantitative analysis of multi-species oral biofilms by TaqMan Real-Time PCR.
Oral infectious diseases, including dental caries, various forms of periodontitis and oral malodor, are not caused by a single pathogen. The etiology of these diseases is known to be associated with bacterial accumulation and plaque composition on the hard and soft tissues of the oral cavity. Therefore, the quantitative, as well as qualitative, analysis of the microorganisms present in oral biofilms, namely dental plaque, subgingival plaque and tongue debris, is important for diagnosis and rational treatment decisions. The quantitative microbial analysis of oral multi-species biofilms also provides useful information for establishing the etiology of oral infectious diseases. Recently, a 5' fluorogenic, nuclease-based, real-time polymerase chain reaction (PCR) technique has been increasingly employed for the quantitative microbial assessment of the human oral cavity. We review the development and use of TaqMan real-time PCR for quantifying oral bacteria, its role in the diagnosis of oral infectious diseases and their microbial etiology.


Early life adversity and adolescent sleep problems during the COVID-19 pandemic.
The COVID-19 pandemic resulted in a reorganization of adolescents' routines, especially their sleep schedules. Utilising 175 caregiver-adolescent dyads, the current study examined associations of biological (e.g., prenatal substance use), environmental (e.g., poverty), and relational (e.g., child maltreatment) subtypes of early life adversity (ELA) with various components of adolescents' sleep across the first year of the COVID-19 pandemic. Relational ELA explained unique variance in adolescents' sleep disturbances, but not other sleep components, following short- and longer-term exposure to the COVID-19 pandemic. However, the direction of this association switched such that relational ELA predicted decreased sleep disturbances during the initial phase of the U.S. COVID-19 pandemic in spring 2020 beyond pre-pandemic levels, but, over time, contributed to increased sleep disturbances beyond early-pandemic levels as the pandemic extended into the winter of 2020.


The effect of targeted exercise on knee-muscle function in patients with persistent hamstring deficiency following ACL reconstruction - study protocol for a randomized controlled trial.
Anterior cruciate ligament (ACL) reconstruction, using hamstring auto-graft is a common surgical procedure, which often leads to persistent hamstring muscle-strength deficiency and reduced function. The purpose of this randomized controlled trial (RCT) is to investigate the effect of a combined, progressive, strength and neuromuscular exercise intervention on knee muscle strength, functional capacity and hamstring muscle-tendon morphology in ACL-reconstructed patients with persistent hamstring muscle-strength deficiency compared with controls. The study is designed as a multicenter, parallel-group RCT with balanced randomization (1:1) and blinded outcome assessments (level of evidence: II) and will be reported in accordance with the CONSORT Statement. Fifty ACL-reconstructed patients (hamstring auto-graft) with persistent limb-to-limb knee-flexor muscle-strength asymmetry at 12-24 months' post surgery, will be recruited through outpatient clinics and advertisements. Patients will be randomized to a 12-week progressive, strength and neuromuscular exercise group (SNG) with supervised training twice weekly or a control intervention (CON) consisting of a home-based, low-intensity exercise program. Outcome measures include between-group change in maximal isometric knee-flexor strength (primary outcome) and knee-extensor muscle strength, hamstring-to-quadriceps strength ratios of the leg that has been operated on and Knee injury and Osteoarthritis Outcome Score (KOOS) (secondary outcomes). In addition, several explorative outcomes will be investigated: The International Knee Documentation Committee Subjective Knee Form (IKDC), the Tegner Activity Score, rate of force development (RFD) for the knee flexors and extensors, tendon regeneration and potential muscle hypertrophy at graft harvest site evaluated by magnetic resonance imaging (MRI), postural control, kinetic/kinematic gait characteristics and knee-related functional capacity. This RCT is designed to investigate the effect of combined, progressive-resistance and neuromuscular exercises on knee-flexor/extensor strength, in the late rehabilitation phase following ACL reconstruction. Reduced hamstring strength represents a potential risk factor for secondary ACL rupture and accelerated progression of osteoarthritis. If deemed effective, the intervention paradigm introduced in this study may help to improve current treatment strategies in ACL-reconstructed patients. ClinicalTrials.gov, ID: NCT02939677 (recruiting). Registered on 20 October 2016.


Neurochemical analysis of cerebrospinal fluid.
The use of cerebrospinal fluid (CSF) analysis for studying in vivo alterations in central neuronal activity requires a relatively sophisticated knowledge of CSF physiology and pathology. Ventriculospinal concentration gradients, circadian rhythms, physical activity, stress, medications, precursor intake, concomitant illness, obstructed CSF circulation, age, and sex alter the baseline neurochemical composition of CSF. Differential probenecid blockade of the egress of acidic monoamine metabolites and cyclic nucleotides from the CSF may complicate interpretations of their accumulations. Degradation of CSF constituents during collection, storage, and analysis may introduce errors in quantification. These sources of CSF variability can be minimized with proper methodolology.


Hydrophobic Water Probed Experimentally at the Gold Electrode/Aqueous Interface.
Quantitative description of reaction mechanisms in aqueous phase electrochemistry requires experimental characterization of local water structure at the electrode/aqueous interface and its evolution with changing potential. Gaining such insight experimentally under electrochemical conditions is a formidable task. The potential-dependent structure of a subpopulation of interfacial water with one OH group pointing towards a gold working electrode is characterized using interface specific vibrational spectroscopy in a thin film electrochemical cell. Such free-OH groups are the molecular level observable of an extended hydrophobic interface. This free-OH interacts only weakly with the Au surface at all potentials, has an orientational distribution that narrows approaching the potential of zero charge, and disappears on oxidation of the gold electrode.


Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators.
Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption.


Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish.
Fibroblast growth factors (Fgfs) regulate critical biological processes such as embryonic development, tissue homeostasis, wound healing, and tissue regeneration. In zebrafish, Fgf signaling plays an important role in the regeneration of the spinal cord, liver, heart, fin, and photoreceptors, although its exact mechanism of action is not fully understood. Utilizing an adult zebrafish extraocular muscle (EOM) regeneration model, we demonstrate that blocking Fgf receptor function using either a chemical inhibitor (SU5402) or a dominant-negative transgenic construct (dnFGFR1a:EGFP) impairs muscle regeneration. Adult zebrafish EOMs regenerate through a myocyte dedifferentiation process, which involves a muscle-to-mesenchyme transition and cell cycle reentry by differentiated myocytes. Blocking Fgf signaling reduced cell proliferation and active caspase 3 levels in the regenerating muscle with no detectable levels of apoptosis, supporting the hypothesis that Fgf signaling is involved in the early steps of dedifferentiation. Fgf signaling in regenerating myocytes involves the MAPK/ERK pathway: inhibition of MEK activity with U0126 mimicked the phenotype of the Fgf receptor inhibition on both muscle regeneration and cell proliferation, and activated ERK (p-ERK) was detected in injured muscles by immunofluorescence and western blot. Interestingly, following injury, ERK2 expression is specifically induced and activated by phosphorylation, suggesting a key role in muscle regeneration. We conclude that the critical early steps of myocyte dedifferentiation in EOM regeneration are dependent on Fgf signaling.


The impact of functional teat number on reproductive throughput in swine.
The objective was to evaluate the impact of functional teat number on reproductive throughput in swine. Data included 735 multiparous Landrace × Large White F1 females. Sow underlined traits consisted of total teat number (TT), functional teat number (FT), nonfunctional teat number (NFT), and number of functional mammary glands (FMG). Weaning traits were calculated for both the biological and the nurse dam. For the biological dam, litter size at weaning (LSW) included a sow's biological piglets regardless of cross-fostering. For nurse dam, number weaned (NW) included the piglets a sow weaned. For the biological dam, piglet survival (PS) was calculated as litter size at weaning / (total number born × 100). Linear regression estimates were calculated in RStudio v. 1.1.456 and variance components were estimated using GIBBS3F90. Average total number born, number born alive, TT, FT, NFT, and FMG were 14.22, 13.12, 14.43, 13.96, 0.42, and 10.7, respectively. An increase in one FT enhanced (P < 0.05) LSW by 0.32 piglets and NW by 0.33 piglets. Similarly, an increase in one FT improved (P < 0.05) PS by 1.63% and reduced (P < 0.05) preweaning mortality by 2.73%. However, an increase in one FT reduced (P < 0.05) average piglet weaning weight (WW) for biological and nurse dams by 35 and 94 g, respectively. Yet an increase in one FT enhanced (P < 0.05) litter weaning weight (LWW) for biological and nurse dams by 1.3 and 1.5 kg, respectively. Heritability estimates for TT, FT, NFT, FMG, WW, LWW, LSW, and PS were 0.25, 0.22, 0.53, 0.18, 0.21, 0.22, 0.16, and 0.18, respectively. Genetic correlation estimates between FT with TT, NFT, and FMG were 0.79, 0.09, and 0.28, respectively. Estimated genetic correlations between TT with WW, LWW, LSW, and PS were 0.37, 0.38, 0.11, and -0.19, respectively. Genetic correlation estimates between FT with WW, LWW, LSW, and PS were 0.44, 0.49, 0.39, and 0.35, respectively. Results suggest increasing functional teat number would enhance both piglet survival and reproductive throughput.


[Recombinant HEV caspid protein p239 specifically attached on HepG2 cells and blocked the infection of wild-type HEV on liver cells].
By using Western blot and immunofluorescence assays, the recombinant HEV capsid protein p239 was found specifically attached to the HepG2 cell surface and entered to the cytoplasm with the increase of incubation temperature. Pre-mixture of wild-type HEV with p239 blocked the infectivity of the virus on primary cultured human hepatocytes and HepG2 cells, indicating that p239 and HEV competed the same targeting site on these cells. These data provide evidence that p239 has a similar cell surface structure with wild-type HEV.


Inhibition of potassium currents is involved in antiarrhythmic effect of moderate ethanol on atrial fibrillation.
Excessive consumption of alcohol is a well-established risk factor of atrial fibrillation (AF). However, the effects of moderate alcohol drinking remain to be elucidated. This study was designed to determine the effects of moderate ethanol ingestion on atrial fibrillation and the electrophysiological mechanisms. In acetylcholine-induced canine and mouse AF models, the moderate ethanol prevented the generation and persistence of AF through prolonging the latent period of AF and shortening the duration of AF. The action potential duration (APD) was remarkably prolonged under the concentration range of 12.5-50.0mM ethanol in guinea pig atrial myocytes. Ultra-rapid delayed rectified potassium currents (IKv1.5) were markedly inhibited by 12.5-50.0mM ethanol in a concentration-dependent manner. Ethanol with 50.0mM could inhibit rapid delayed rectifier potassium currents (IhERG). Ethanol under 6.25-50.0mM did not affect on inward rectifier potassium currents (IKir2.1). Collectively, the present study provided an evidence that moderate ethanol intake can prolong the APD of atrial myocytes by inhibition of IKv1.5 and IhERG, which contributed to preventing the development and duration of AF.


Characterization of surface binding sites in glycoside hydrolases: A computational study.
Structural properties of carbohydrate surface binding sites (SBSs) were investigated with computational methods. Eighty-five SBSs of 44 enzymes in 119 Protein Data Bank (PDB) files were collected as a dataset. On the basis of SBSs shape, they were divided into 3 categories: flat surfaces, clefts, and cavities (types A, B, and C, respectively). Ligand varieties showed the correlation between shape of SBSs and ligands size. To reduce cut-off differences in each SBSs with different ligand size, molecular docking were performed. Molecular docking results were used to refine SBSs classification and binding sites cut-off. Docking results predicted putative ligands positions and displayed dependence of the ligands binding mode to the structural type of SBSs. Physicochemical properties of SBSs were calculated for all docking results with YASARA Structure. The results showed that all SBSs are hydrophilic, while their charges could vary and depended to ligand size and defined cut-off. Surface binding sites type B had highest average values of solvent accessible surface area. Analysis of interactions showed that hydrophobic interactions occur more than hydrogen bonds, which is related to the presence of aromatic residues and carbohydrates interactions.