Therapeutic effects and mechanisms study of Hanchuan Zupa Granule in a Guinea pig model of cough variant asthma.
Hanchuan Zupa Granule (HCZP), a traditional Chinese ethnodrug, has the functions of supressing a cough, resolving phlegm, warming the lungs, and relieving asthma. In clinical practice employing traditional Chinese medicine (TCM), HCZP is commonly used to treat acute colds, cough and abnormal mucous asthma caused by a cold, or "Nai-Zi-Lai" in the Uygur language. Studies have confirmed the use of HCZP to treat cough variant asthma (CVA) and other respiratory diseases. However, the pharmacological mechanisms of HCZP remain unrevealed. To investigate the anti-tussive and anti-asthmatic effects and the possible pharmacological mechanisms of HCZP in the treatment of CVA. A guinea pig CVA animal model was established by intraperitoneal injection of ovalbumin (OVA) combined with intraperitoneal injection of aluminium hydroxide adjuvant and atomized OVA. Meanwhile, guinea pigs with CVA received oral HCZP (at dosages of 0.571, 0.285 and 0.143 g/kg bodyweight). The number of coughs induced by aerosol capsaicin was recorded, and the airway hyperresponsiveness (AHR) of CVA guinea pigs was detected with the FinePointe series RC system. H&E staining of lung tissues was performed to observe pathological changes. ELISA was used to detect inflammatory cytokines. qRT-PCR and western blotting analyses were used to detect the expression of Th1-specific transcription factor (T-bet), Th2-specific transcription factor (GATA3), and Toll-like receptor 4 (TLR4) signal transduction elements. These methods were performed to assess the protective effects and the potential mechanisms of HCZP on CVA. Great changes were found in the CVA guinea pig model after HCZP treatment. The number of coughs induced by capsaicin in guinea pigs decreased, the body weights of guinea pigs increased, and inflammation of the eosinophilic airway and AHR were reduced simultaneously. These results indicate that HCZP has a significant protective effect on CVA. A pharmacological study of HCZP showed that the levels of interleukin-4 (IL-4) and IL-5 and tumour necrosis factor-α (TNF-α) in serum decreased. The amount of interferon-γ (IFN-γ) increased, mRNA and protein expression of TLR4 and GATA3 weakened, and mRNA and protein expression of T-bet increased. HCZP ameliorated the symptoms of guinea pigs with CVA induced by OVA by regulating the Th1/Th2 imbalance and TLR4 receptors.


Transcriptional control of neuronal diversification in the retina.
During embryonic development, the array of vastly different neuronal types that are incorporated into the functional architecture of the mature neuroretina derives from a common population of multipotent retinal progenitor cells (RPCs). Retinogenesis proceeds in a precise chronological order, with the seven principal cell classes generated in successive phases. Cell biological experiments established that this histogenetic order, at least in part, reflects intrinsic changes within the RPC pool. In recent years a number of molecules controlling various aspects of cell fate specification from RPCs have been identified. However, few attempts have been made to integrate previous concepts that emerged from cell biological studies and more recent results based on molecular genetic experiments. This review aims at providing an overview of recent advances in our understanding of the cellular and molecular mechanisms underlying retinal neuronal diversification, with a particular focus on cell-intrinsic factors.


Characteristics of vaccinating providers reported through Medicare claims in office-based settings: Volume of influenza and pneumococcal vaccinations.
Vaccination coverage among older adults is low in the United States. A recommendation from a provider is a strong predictor of vaccine receipt. Using Medicare Fee-For-Service data (2015-2017) this study characterized providers by the number of influenza and pneumococcal vaccines administered in physician offices, age, gender, and professional specialty to determine the volume of vaccines provided by individual providers and characteristics of these providers. Half of all vaccinations were provided by 10% of providers. The mean age of 224,483 and 165,710 unique influenza and pneumococcal providers respectively was 49 years (SD: 12 years) with males and females equally distributed. The highest vaccinating quartile of providers tended to be older, more likely male and more likely general physicians. Those who administered a high volume of one vaccine were likely to administer a high volume of the other. Providers administering vaccines in office-based settings can do more to increase vaccination coverage rates.


Facial nerve prognostication in vestibular schwannoma surgery: the concept of percent maximum and its predictability.
To evaluate percent maximum as an intraoperative facial nerve measurement for the long-term prognostication of vestibular schwannoma surgery. Prospective cohort study. Evoked amplitude responses to varying levels of stimulus intensity at the nerve root were compared to their supramaximal responses (Mmax) as a percentage, that is, percent maximum. Response charts were constructed for each of the levels of stimulus intensity between 0.05 to 0.3 mA, vis-à-vis facial nerve outcome at 1 year, to establish sensitivities, specificities, and positive predictive values. Logistic regression analyses were used to determine the impact of sex, age, tumor size, and historically defined response parameter on outcomes. Seventy-eight patients who underwent vestibular schwannoma surgeries between 2005 and 2010 were studied. The positive predictive value (PPV) of a good facial nerve outcome, defined as House-Brackmann (HB) I-II, increases with percent maximum responses. A 90% PPV could be established when the response amplitude was 50% or greater compared to Mmax. Long-term prognostication appeared best at a higher stimulus level of 0.3 mA. Age and sex did not have an impact on outcome, but tumor size did; with each centimeter increase in tumor size, patients were 105% more likely to have a poor outcome (HB III-VI). If the response parameter "≥240 μV at 0.05 mA" was not present, there was a trend toward poor outcome. Percent maximum is a valid intraoperative monitoring measure to prognosticate long-term facial nerve outcome. It should be considered a complementary method of monitoring when evoked responses do not conform to conventional predictors. 4.


Investigating the candidacy of a lipoteichoic acid-based glycoconjugate as a vaccine to combat Clostridium difficile infection.
A lipoteichoic acid has recently been shown to be conserved in the majority of strains from Clostridium difficile and as such is being considered as a possible vaccine antigen. In this study we examine the candidacy of the conserved lipoteichoic acid by demonstrating that it is possible to elicit antibodies against C. difficile strains following immunisation of rabbits and mice with glycoconjugates elaborating the conserved lipoteichoic acid antigen. The present study describes a conjugation strategy that utilises an amino functionality, present at approximately 33 % substitution of the N-acetyl-glucosamine residues within the LTA polymer repeating unit, as the attachment point for conjugation. A maleimide-thiol linker strategy with the maleimide linker on the carboxyl residues of the carrier protein and the thiol linker on the carbohydrate was employed. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, despite an immune response to the linkers also being observed. These sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has illustrated that the LTA polymer is a highly conserved surface polymer of C. difficile that is easily accessible to the immune system and as such merits consideration as a vaccine antigen to combat C. difficile infection.


[Urination habits and urinary tract infections in girls. 3. Dependency of therapy results from length of therapy and from urination habits].
Urinary tract infections in girls are promoted by abnormal micturition habit. Aside from applying antibiotics, the training of voiding discipline is very important for UTI prevention. The duration of medicamentous prevention should pay regard to the behaviour of micturition.


Life-threatening flecainide overdose treated with intralipid and extracorporeal membrane oxygenation.
Flecainide is a Class Ic antiarrythmic agent associated with adverse events due to its pro-arrythmic effects. We report the case of a 33-year-old female presenting in cardiac arrest after a flecainide overdose treated with intravenous fat emulsion (IFE), sodium bicarbonate (NaHCO₃), and extracorporeal membrane oxygenation (ECMO). This case reviews the pathophysiology and management of flecainide toxicity including novel strategies of IFE and ECMO.


Efficient synthesis, structure, and antimicrobial activity of some novel N- and S-beta-D-glucosides of 5-pyridin-3-yl-1,2,4-triazoles.
Glucosidation of some 4-amino- and 4-arylideneamino-5-(pyridin-3-yl)-2,4-dihydro-[1,2,4]-triazole-3-thiones with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide followed by chromatographic separation gave the corresponding N- and S-beta-D-glucosides. The structure of these two regiosiomers was established chemically and spectroscopically. Deamination as well as deacetylation of some selected nucleosides have been achieved. Antimicrobial screening of 14 selected compounds resulted in their activity against Aspergillus fumigatus, Penicillium italicum, Syncephalastrum racemosum, Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, and Escherichia coli.


Diagnosis of visceral leishmaniasis in Ceará state, Brazil: A flow analysis of cases between 2007 and 2021.
To analyse the flow of cases of visceral leishmaniasis (VL) in the state of Ceará, Brazil, between 2007 and 2021. An ecological study was conducted using a spatial approach of newly confirmed cases of VL recorded in the Notifiable Diseases Information System. We identified individuals whose municipality of diagnosis differed from that of their residence. Flow maps, constructed using Tabwin 32 and ArcMap 9.2, allowed for the identification of the volume of traffic between the municipality of residence and that of initial care. There were 6775 confirmed VL cases. As a flow indicator, 178 counties had at least one resident diagnosed in another municipality in Ceará, with 2491 VL cases and an average trip of 79 km. The largest hub for receiving cases for diagnosis was the capital Fortaleza (1478 patients from 129 other municipalities), followed by Sobral, located in the northwestern region of Ceará (599 from 55 municipalities), and Barbalha, in the southern region (171 from 29 municipalities). In this southern region, 25 municipalities moved 55 people for treatment to Juazeiro do Norte and 11 municipalities moved 39 patients to Crato. A total of 255 patients with VL from 11 municipalities in other Brazilian states, mainly from the Northeast and North, were observed and notified in health services in Ceará. The major centres of VL diagnosis outside residence were in the cities of Fortaleza, Sobral, Barbalha, Juazeiro do Norte and Crato. There was also an outflow of cases from other municipalities located in the northeastern and northern regions of Brazil. The flows were more intense during the first triennium of the analysis and milder from 2019 to 2021. Understanding the diagnostic flow of VL helps in decision making and the development of public policies to improve the lives of the population.


Seven-year experience with polytetrafluoroethylene as above-knee femoropopliteal bypass graft. Is is worthwhile to preserve the autologous saphenous vein?
A 7-year experience with 90 polytetrafluoroethylene (PTFE) femoropopliteal bypass grafts in the above-knee (AK) position is presented. The 5- and 7-year actuarial patency rate was 58.3%. No statistical difference was found between the patency rate of this series and that of a group of 17 AK and 77 below-knee (BK) femoropopliteal bypass grafts performed during the same period with the autologous saphenous vein (ASV). During the follow-up period (range 6 to 84 months, mean 42 months) a new bypass in a more distal location was required in 20 limbs. The ASV was available in seven of the eight PTFE graft failures and in only one of the 12 ASV failures. The 3-year patency rate of these new groups was 58.3% and 16.7%, respectively (p less than 0.02). Eighteen of the 48 deaths occurring during the follow-up period were related to atherosclerotic heart disease, whereas only one patient underwent coronary artery bypass grafting. Five hundred patients randomly selected from our series of myocardial revascularization procedures were reviewed. In five a femorodistal reconstruction was performed before coronary artery bypass, and in only two (0.4%), the ASV was not available. PTFE use in the AK position may be a reasonable alternative to the ASV to preserve it for additional treatment of more distal occlusive disease. There is no evidence that such a need exists for further treatment of coronary artery disease.


Molecular designing of naphthalene diimide based fullerene-free small organic solar cell - Acceptors with high photovoltaic performance by density functional theory.
With the help of computational chemistry tools, three non-fullerene acceptors, which are 2-methylene-malononitrile (M-1), 2-(3-methyl-5-methylene-2-thioxothiazolidin-4-ylidene) malononitrile (M-2) and 1-methyl-5-methylene-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile (M-3), are designed with naphthalene diimide (NDI) central unit. Their different photovoltaic and optoelectronic properties like absorption spectrum, electrons density, solubility strength, reorganization energies, % ETC from donor to acceptor part, excitation energies, oscillating strength, morphology and crystallinity of device for constructing the thin film bulk hetro junction devices were computed at the WB97XD/6-31 G (d, p) level of density functional theory (DFT). Expected open circuit voltages of designed molecules are high as 4.05 eV to 4.49 eV, which are significantly larger than that of the previously reported 3-methyl-5-methylene-2-thioxothiazolidin-4-one (R) with the value of 3.60 eV at the zero current level. Charge carrier mobilities of designed molecules are high due to having low re-organization energies varying from 0.0163 eV to 0.0280 eV for electron and 0.0160 eV to 0.0190 eV for hole, strong absorption properties between the 420 nm to 550 nm in chloroform and 400 nm to 540 nm in gas phase conditions, respectively.


Impaired translocation and activation of mitochondrial Akt1 mitigated mitochondrial oxidative phosphorylation Complex V activity in diabetic myocardium.
Insulin can translocate Akt to mitochondria in cardiac muscle. The goals of this study were to define sub-mitochondrial localization of the translocated Akt, to dissect the effects of insulin on Akt isoform translocation, and to determine the direct effect of mitochondrial Akt activation on Complex V activity in normal and diabetic myocardium. The translocated Akt sequentially localized to the mitochondrial intermembrane space, inner membrane, and matrix. To confirm Akt translocation, in vitro import assay showed rapid entry of Akt into mitochondria. Akt isoforms were differentially regulated by insulin stimulation, only Akt1 translocated into mitochondria. In the insulin-resistant Type 2 diabetes model, Akt1 translocation was blunted. Mitochondrial activation of Akt1 increased Complex V activity by 24% in normal myocardium in vivo and restored Complex V activity in diabetic myocardium. Basal mitochondrial Complex V activity was lower by 22% in the Akt1(-/-) myocardium. Insulin-stimulated Complex V activity was not impaired in the Akt1(-/-) myocardium, due to compensatory translocation of Akt2 to mitochondria. Akt1 is the primary isoform that relayed insulin signaling to mitochondria and modulated mitochondrial Complex V activity. Activation of mitochondrial Akt1 enhanced ATP production and increased phosphocreatine in cardiac muscle cells. Dysregulation of this signal pathway might impair mitochondrial bioenergetics in diabetic myocardium.


Recent advances in solid-state relaxation dispersion techniques.
This review describes two rotating-frame (R1ρ) relaxation dispersion methods, namely the Bloch-McConnell Relaxation Dispersion and the Near-rotary Resonance Relaxation Dispersion, which enable the study of microsecond time-scale conformational fluctuations in the solid state using magic-angle-spinning nuclear magnetic resonance spectroscopy. The goal is to provide the reader with key ideas, experimental descriptions, and practical considerations associated with R1ρ measurements that are needed for analyzing relaxation dispersion and quantifying conformational exchange. While the focus is on protein motion, many presented concepts can be equally well adapted to study the microsecond time-scale dynamics of other bio- (e.g. lipids, polysaccharides, nucleic acids), organic (e.g. pharmaceutical compounds), or inorganic molecules (e.g., metal organic frameworks). This article summarizes the essential contributions made by recent theoretical and experimental solid-state NMR studies to our understanding of protein motion. Here we discuss recent advances in fast MAS applications that enable the observation and atomic level characterization of sparsely populated conformational states which are otherwise inaccessible for other experimental methods. Such high-energy states are often associated with protein functions such as molecular recognition, ligand binding, or enzymatic catalysis, as well as with disease-related properties such as misfolding and amyloid formation.


Persistent bloodstream infection with Kocuria rhizophila related to a damaged central catheter.
A case of persistent bloodstream infection with Kocuria rhizophila related to a damaged central venous catheter in a 3-year-old girl with Hirschsprung's disease is reported. The strain was identified as K. rhizophila by 16S rRNA gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Arbitrarily primed PCR analysis showed a clonal strain. The repeated septic episodes were resolved with the catheter repair.


cDNA representational difference analysis of ileal Peyer's patches in lambs after oral inoculation with scrapie.
cDNA representational difference analysis (RDA) was used to study gene expression profiles in the ileal Peyer's patch of a lamb 1 week after oral inoculation with the scrapie agent. Twenty-five differentially expressed cDNA fragments were identified and cloned. Sequence analysis indicated seven novel gene sequences. Other clones shared sequence homology with genes encoding ribosomal and mitochondrial proteins, the translation initiation factor EIF4GII and the bovine pancreatic thread protein. Reverse Northern was used to confirm the differential expression in another four lambs inoculated with scrapie and the tissue distribution of the novel genes was examined using Northern blot analysis.


Effect of infection with Aeromonas hydrophila on antioxidant capacity, inflammation response, and apoptosis proteins in Chinese mitten crab (Eriocheir sinensis).
Aeromonas hydrophila (A. hydrophila) as a serious bacterial disease endangering aquaculture and the Chinese mitten crabs (Eriocheir sinensis) industry. The present study was conducted to investigate the effects of A. hydrophila on the antioxidant, inflammation, immunity and apoptosis of the E. sinensis. The E. sinensis (female: 150 crabs and male: 150 crabs; 67.11 ± 0.76 g) were randomly divided into the control group (Foot injection with 200 μl PBS) and infection group (Foot injection with 200 μl A. hydrophila of 106 cfu/mL). The hepatopancreas and serum was collected to detect the related indicators after injection 24 h. The results showed that A. hydrophila significantly reduced the malondialdehyde (MDA) level and gamma-glutamyl-cysteine synthetase (γ-GCS) activity in the hepatopancreas of male and female crabs (P < 0.05). A.hydrophila also significantly decreased the total-superoxide dismutase (T-SOD) activity while the levels of total antioxidant capacity (T-AOC) and total glutathione (T-GSH) were significantly increased in the hepatopancreas and serum of male crabs (P < 0.05). At the transcriptional level, the expression of catalase (CAT) and glutathione peroxidases (GPx), Glutathione S-transferase (GST) in the hepatopancreas of male and female crabs was significantly reduced compared to the control group (P < 0.05). However, A. hydrophila could not significantly change the Kelch-like ECH-associated protein 1 (Keap1) gene expression level in both of male and female carbs. A. hydrophila injection for 24 h, the lysozyme (LZM) and phenoloxidase (PO) activity was significantly increased in the hepatopancreas and serum of the male and female crabs (P < 0.05). Simultaneous increase of immune-related enzyme activity (acid phosphatase and alkaline phosphatase) was found in the serum of male and female crabs (P < 0.05). However, the acid phosphatase (ACP) and alkaline phosphatase (ALP) activity was significantly decreased in the hepatopancreas of male and female crabs (P < 0.05). Meanwhile, the LZM mRNA level was significantly decreased in the hepatopancreas of E. sinensis (P < 0.05). Furthermore, A. hydrophila significantly inhibited the mRNA expression of immune regulated factors (Interleukin enhancer binding factor 2: ILF2, interleukin-16: IL-16, Toll-like receptor: TLR) in the male and female crabs. The levels of inflammatory cytokines (interleukin-1β: IL-1β, interleukin-6: IL-6, interleukin-8: IL-8, interleukin-10: IL-10) were significantly increased in the hepatopancreas of male and female crabs. Moreover, A.hydrophila increased the mRNA expression of apoptosis - related genes in male crabs (p38 mitogen-activated protein kinase: p38, adamalysin 17: ADAM17, Cysteine-aspartic acid protease 3: Caspase 3, and Bcl-2-associated X: BAX), but reduced the expression of p38, ADAM17, Caspase 3 and BAX genes in female crabs. In conclusion, A. hydrophila could induce oxidative stress and the response of inflammation and immunity, and also trigger the mRNA expression changes of apoptosis related-genes in E. sinensis. This study provides a theoretical basis for the study of E. sinensis diseases.


Microprofiling of nitrogen patches in paddy soil: Analysis of spatiotemporal nutrient heterogeneity at the microscale.
Flooded paddy soil ecosystems in the tropics support the cultivation of the majority of the world's leading crop, rice, and nitrogen (N) availability in the paddy-soil rooting zone limits rice production more than any other nutritional factor. Yet, little is known about the dynamic response of paddy soil to N-fertiliser application, in terms of horizontal and vertical patchiness in N distribution and transformation. Here, we present a microscale analysis of the profile of ammonium (NH4(+)) and nitrate (NO3(-)), nitrification, oxygen (O2water and O2soil), and pH (pHwater and pHsoil) in paddy soils, collected from two representative rice-production areas in subtropical China. NH4(+) and NO3(-) exhibited dramatic spatiotemporal profiles within N patches on the microscale. We show that pHsoil became constant at 1.0-3.5 mm depth, and O2soil became undetectable at 1.7-4.0 mm. Fertiliser application significantly increased pH, and decreased O2, within N patches. Path analysis showed that the factors governing nitrification scaled in the order: pHwater > pHsoil > NH4(+) > O2water > NO3(-) > O2soil. We discuss the soil properties that decide the degree of nutrient patchiness within them and argue that such knowledge is critical to intelligent appraisals of nutrient-use efficiencies in the field.


Forebrain monoamines and associative learning: I. Latent inhibition and conditioned inhibition.
Two experiments evaluated the effects of depletion of forebrain norepinephrine (NE) or serotonin (5-HT) on two forms of internal inhibition. Experiment 1 examined the role of NE and 5-HT depletion on latent inhibition: rats with dorsal bundle or raphe lesions or vehicle control rats were trained to one of two pre-exposure conditions (single vs multiple stimuli) or to a non-pre-exposure control prior to conditioning. The results of this experiment showed that latent inhibition was attenuated under either condition of pre-exposure following depletion of 5-HT but that attenuation was present in NE depleted rats only when pre-exposed to multiple stimuli. Experiment 2 assessed the rate at which a conditioned inhibitor was established following NE or 5-HT depletion. The results of Experiment 2 indicated that the formation of a conditioned inhibitor was unimpaired following depletion of either NE or 5-HT. The results of Experiment 1 demonstrate that 5-HT and NE have different effects on associative processes: 5-HT apparently affects a habituation-like process, whereas NE is an important influence on more complex mechanisms involving the comparison of new with previously acquired information. The findings of Experiment 2 are consistent with behavioral investigations which show that conditioned inhibition affects output processes rather than the salience of stimuli.


Simple Preparation Method for Hydrophilic/Oleophobic Coatings.
This work provides a simple method to prepare a hydrophilic/oleophobic coating using polyester filter cloth as the substrate, a mixture of three hydrophilic polymers (poly(aspartic acid), poly(acrylic acid), and poly(vinyl alcohol)); SiO2 with an average particle size of 30 nm is used to improve the surface roughness of the filter cloth. Then, a long fluorocarbon chain of 1H,1H,2H,2H-perfluorooctyltriethoxysilane is grafted onto the surface by a vacuum silanization coupling reaction to obtain hydrophilic/oleophobic properties. The water and hexadecane contact angles of the treated filter cloth are 3 and 99.8°, respectively. A separation efficiency of 98% was achieved in hexadecane/water separation. The durability test shows that the separation efficiency of toward hexadecane-water mixture remains more than 98% after 20 cycles. The obtained material also presents a strong underwater antipollution property when using hexane, rapeseed oil, mineral oil, and pump oil as model pollutants. For oils with higher viscosity, the separation efficiency remains above 97%. However, the separation efficiency is ∼80% when treating emulsions.


Characterization of a SILAC method for proteomic analysis of primary rat microglia.
Microglia play important and dynamic roles in mediating a variety of physiological and pathological processes during the development, normal function and degeneration of the central nervous system. Application of SILAC-based proteomic analysis would greatly facilitate the identification of cellular pathways regulating the multifaceted phenotypes of microglia. We and others have successfully SILAC-labeled immortalized murine microglial cell lines in previous studies. In this study, we report the development and evaluation of a SILAC-labeled primary rat microglia model. Although the isotope labeling scheme for primary microglia is drastically different from that of immortalized cell lines, our de novo and uninterrupted primary culture labeling protocol (DUP-SILAC) resulted in sufficient incorporation of SILAC labels for mass spectrometry-based proteomic profiling. In addition, label incorporation did not alter their morphology and response to endotoxin stimulation. Proteomic analysis of the endotoxin-stimulated SILAC-labeled primary microglia identified expected as well as potentially novel activation markers and pro-inflammatory pathways that could be quantified in a more physiologically relevant cellular model system compared to immortalized cell lines. The establishment of primary microglia SILAC model will further expand our capacity for global scale proteomic profiling of pathways under various physiological and pathological conditions. Proteomic MS data are available via ProteomeXchange with identifier PXD002759.


The application of a DNA-based identification technique to over-the-counter herbal medicines.
Reliable methods to identify medicinal plant material are becoming more important in an increasingly regulated market place. DNA-based methods have been recognised as a valuable tool in this area with benefits such as being unaffected by the age of the plant material, growth conditions and harvesting techniques. It is possible that the methods of production used for medicinal plant products will degrade or remove DNA. So how applicable are these techniques to processed medicinal plant products? A simple PCR-based identification technique has been developed for St. John's Wort, Hypericum perforatum L. Thirteen St. John's Wort products were purchased including capsules, tablets and tinctures. DNA was extracted from each product, and the species specific PCR test conducted. DNA was successfully extracted from all thirteen products, using a fast and efficient modified method for extracting DNA from tinctures. Only four products yielded the full length ITS region (850 bp) due to the quality of the DNA. All of the products tested positive for H. perforatum DNA. DNA-based identification methods can complement existing methods of authentication. This paper shows that these methods are applicable to a wide range of processed products, provided that they are designed to account for the possibility of DNA degradation.


Influence of endogenous prostaglandins on secretin-mediated inhibition of gastric acid secretion in dogs.
The influence of endogenous prostaglandins on secretin-mediated inhibition of gastric acid secretion was examined in 6 mongrel dogs with Thomas gastric and Herrera pancreatic cannulas. The dogs were given intravenous pentagastrin (1 microgram/kg.h) during the 180-min experiment, and graded doses of secretin (0.3-1.5 micrograms/kg.h) (1-5 CU/kg.h) were infused intravenously between 60 and 120 min. In alternate, otherwise identical experiments, a prostaglandin synthesis inhibitor, either indomethacin or meclofenamate, was also administered throughout the experiment. Increasing doses of secretin led to increasing inhibition of gastric acid output with the maximum inhibition at 1 microgram/kg.h (3.3 CU/kg.h) of secretin. Both indomethacin and meclofenamate abolished the inhibitory effects of secretin on gastric acid secretion. The inhibitors of prostaglandin generation had no effect on the serotonin system. We concluded that secretin mediates its inhibitory action on gastric acid secretion, at least in part, through endogenous prostaglandins.


Spatially resolved extended phase graphs: modeling and design of multipulse sequences with parallel transmission.
A spatially resolved extended phase graph (SR-EPG) framework is proposed for prediction of echo amplitudes in the presence of spatially variable radio frequency (RF) fields. The method may be used to examine any regularly repeating pulse sequence and provides a design framework for parallel transmission (PTx) systems; in this work signal homogeneity in static pseudo-steady state (SPSS) turbo spin echo (TSE) imaging was investigated. Building on SR-EPG calculations with PTx, a dynamic RF-shimming approach is proposed in which, RF pulse amplitudes and phases are optimized on a per channel and per pulse basis to yield the desired signal response for all echoes. Results show significant improvements over "static" RF shimming (in which the relative amplitude/phase of the PTx channels are fixed for all pulses). SPSS-TSE imaging using dynamic RF shimming resulted in excellent image quality, both in phantoms and in vivo, and confirmed SR-EPG predictions.


Failure to thrive--tackling feeding problems: a community-based approach.
Failure to thrive rings fewer alarm bells these days in comparison with other concerns such as child sexual abuse. Yet, writes Diana Hampton, it remains a significant source of anxiety to parents and professionals working in child health and development. Here she describes a Children's Society project which aims to tackle the problem of failure to thrive through one-to-one work with families in their own homes.


Structure-based prediction of Major Histocompatibility Complex (MHC) epitopes.
Because of the enormous diversity of both MHC proteins and peptide epitopes, computational epitope prediction methods are needed in order to supplement limited experimental data. These prediction methods are useful for guiding experiments and have many potential biomedical applications. Unlike popular sequence-based methods, structure-based epitope prediction methods can predict epitopes for multiple MHC types with highly distinct peptide binding propensities. In this chapter, we describe in detail our previously developed structure-based epitope prediction methods for both class I and class II MHC proteins. We also discuss the relative advantages and disadvantages of sequence-based versus structure-based methods and how to evaluate prediction performance.


Operative results of coronary artery bypass grafting in women.
The relative mortality of coronary artery bypass grafting (CABG) surgery in women is not certain. The purpose of this study was to examine the results of primary, isolated CABG in a series of Taiwanese female patients. Medical records of 2055 patients (188 women and 1867 men), who underwent primary, isolated CABG at Taipei Veterans General Hospital from January 1, 1991 to December 31, 1999, were reviewed. The mortality rate, associated with clinical and operative variables, was compared between female and male patients. The female patients had more diabetes (51.6% vs. 29.9%, P<0.01), more hypertension (77.1% vs. 65.0%, P<0.01), and more hypercholesterolemia (39.4% vs. 29.6%, P<0.01), as compared with men. Fewer women consumed cigarette smoking (17.0% vs. 52.1%, P<0.001). Fewer internal mammary artery grafts were used in women (43.1% vs. 57.3%, P<0.001). Nine female (4.8%) and 93 male patients (5.0%) died. There was no significant difference in hospital mortality between women and men. Other variables, including age, angina class, NYHA class, incidence of peripheral arterial occlusive disease, stenosis of left main coronary artery, number of stenotic coronary arteries, incidence of emergent operations, anastomosis number, aortic cross-clamping time, cardiopulmonary bypass time, and left ventricular ejection fraction, were not significantly different between female and male patients. Although the female patients were more frequently diabetic, hypertensive, and hypercholesterolemic, the hospital mortality of CABG in women was not significantly different from that in men. This result supports an aggressive surgical treatment for women with coronary artery disease.


Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation.
We sought to elucidate the role of AKT in follicle-stimulating hormone (FSH)-mediated granulosa cell (GC) differentiation. Our results define a signaling pathway in GCs whereby the inactivating phosphorylation of tuberin downstream of phosphatidylinositol (PI) 3-kinase/AKT activity leads to Rheb (Ras homolog enriched in brain) and subsequent mTOR (mammalian target of rapamycin) activation. mTOR then stimulates translation by phosphorylating p70 S6 kinase and, consequently, the 40 S ribosomal protein S6. Activation of this pathway is required for FSH-mediated induction of several follicular differentiation markers, including luteinizing-hormone receptor (LHR), inhibin-alpha, microtubule-associated protein 2D, and the PKA type IIbeta regulatory subunit. FSH also promotes activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). FSH-stimulated HIF-1 activity is inhibited by the PI 3-kinase inhibitor LY294002, the Rheb inhibitor FTI-277 (farnesyltransferase inhibitor-277), and the mTOR inhibitor rapamycin. Finally, we find that the FSH-mediated up-regulation of reporter activities for LHR, inhibin-alpha, and vascular endothelial growth factor is dependent upon HIF-1 activity, because a dominant negative form of HIF-1alpha interferes with the up-regulation of these genes. These results show that FSH enhances HIF-1 activity downstream of the PI 3-kinase/AKT/Rheb/mTOR pathway in GCs and that HIF-1 activity is necessary for FSH to induce multiple follicular differentiation markers.


Kinetic and calorimetric study of the adsorption of dyes on mesoporous activated carbon prepared from coconut coir dust.
Mesoporous activated carbon has been prepared from coconut coir dust as support for adsorption of some model dye molecules from aqueous solutions. The methylene blue (MB) and remazol yellow (RY) molecules were chosen for study of the adsorption capacity of cationic and anionic dyes onto prepared activated carbon. The adsorption kinetics was studied with the Lagergren first- and pseudo-second-order kinetic models as well as the intraparticle diffusion model. The results for both dyes suggested a multimechanism sorption process. The adsorption mechanisms in the systems dyes/AC follow pseudo-second-order kinetics with a significant contribution of intraparticle diffusion. The samples simultaneously present acidic and basic sites able to act as anchoring sites for basic and acidic dyes, respectively. Calorimetric studies reveal that dyes/AC interaction forces are correlated with the pH of the solution, which can be related to the charge distribution on the AC surface. These AC samples also exhibited very short equilibrium times for the adsorption of both dyes, which is an economically favorable requisite for the activated carbon described in this work, in addition to the local abundance of the raw material.


Personality patterns of adolescent poor and good sleepers.
To determine whether poor sleepers have a unique personality constellation significantly different from that of good sleepers, a sample of 162 emotionally disturbed adolescent poor sleepers was compared to a sample of 153 emotionally disturbed adolescent good sleepers on standardized personality instruments. Poor sleepers were found to have a high incidence of neurotic psychopathology with personality patterns characterized by depression, fearfulness, inhibition, anxiety, and rumination. In contrast, good sleepers showed quasi-healthy and/or characterological patterns. While this study does not resolve cause and effect relationships, it does establish a highly significant relationship between neuroticism and sleep disturbance for adolescent boys and girls, and also demonstrates a similarity of personality dynamics and patterns between adult and adolescent samples of patients with sleep disturbances.


Synthesis, spectroscopy, electrochemistry and thermogravimetry of copper(II) tridentate Schiff base complexes, theoretical study of the structures of compounds and kinetic study of the tautomerism reactions by ab initio calculations.
Attempts to spectroscopic and structural study of copper complexes, some Cu(II) Schiff base complexes were synthesized and characterized by means of electronic, IR, (1)HNMR spectra and elemental analysis. The thermal analyses of the complexes were investigated and the first order kinetic parameters were derived for them. The cyclic voltammetric studies in acetonitrile were proposed a monomeric structure for complexes. The structures of compounds were determined by ab initio calculations. In the solid state, the ligands exist as keto-amine/enol-imine tautomeric forms with an intramolecular hydrogen bond (N-H···O) between amine and carbonyl group. The kinetic studies of the tautomerism and equilibrium constant of the reactions were calculated using transition state theory. The optimized molecular geometry and atomic charges were calculated using MP2 method with 6-31G(d) basis set for H, C, N and O atoms and LANL2DZ for the Cu atom. The results suggested that, in the complexes, Cu(II) ion is in pseudo square-planar NO(3) coordination geometry. Also the bond lengths and angles were studied and compared.


A case report of persistent drug-sensitive pulmonary tuberculosis after treatment completion.
Mycobacterium tuberculosis (Mtb) has been found to persist within cavities in patients who have completed their anti-tuberculosis therapy. The clinical implications of Mtb persistence after therapy include recurrence of disease and destructive changes within the lungs. Data on residual changes in patients who completed anti-tuberculosis therapy are scarce. This case highlights the radiological and pathological changes that persist after anti-tuberculosis therapy completion and the importance of achieving sterilization of cavities in order to prevent these changes. This is a case report of a 33 year old female with drug-sensitive pulmonary tuberculosis who despite successfully completing standard 6-month treatment had persistent changes in her lungs on radiological imaging. The patient underwent multiple adjunctive surgeries to resect cavitary lesions, which were culture positive for Mtb. After surgical treatment, the patient's chest radiographies improved, symptoms subsided, and she was given a definition of cure. Medical therapy alone, in the presence of severe cavitary lung lesions may not be able to achieve sterilizing cure in all cases. Cavities can not only cause reactivation but also drive inflammatory changes and subsequent lung damage leading to airflow obstruction, bronchiectasis, and fibrosis. Surgical removal of these foci of bacilli can be an effective adjunctive treatment necessary for a sterilizing cure and improved long term lung health.


Procedural and clinical outcomes after use of the glycoprotein IIb/IIIa inhibitor abciximab for saphenous vein graft interventions.
Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) poses a high-risk for distal coronary thromboembolic events. Glycoprotein IIb/IIIa inhibitors are frequently used in hope of reducing the impact of this, although the safety and efficacy of these drugs to improve outcomes in this setting are understudied. Patients were included if they had prior coronary artery bypass surgery and subsequently underwent PCI of ≥1 SVG graft at a Dutch academic center between 1997 and 2008. These patients were matched 1:1 based on peri-procedural use of abciximab using a propensity-score matching algorithm based on 17 variables. Conditional logistic regression and Cox regression stratified on matched pairs were performed to evaluate the association between abciximab use and MACCE (the composite measure of mortality, myocardial infarction, stroke and repeat revascularization) at 30days and up to 1year. The composite of 30-day MACCE occurred in 18 patients (15.3%) in the abciximab group and 16 patients (13.6%) in the propensity matched control group (OR: 1.13, 95% CI: 0.57-2.21, p=0.73). At 1-year follow-up, MACCE rates were also similar (32.5% vs. 33.9%, HR: 0.97, 95% CI: 0.59-1.59). Major bleeding (BARC types 3a-c) was higher in the abciximab group (11.9% vs. 4.2%, OR: 2.80, 95% CI: 1.01-7.77). Ischemic outcomes did not differ among patients with acute coronary syndromes. The use of intravenous abciximab was not associated with improved clinical outcomes up to 1-year among patients undergoing SVG PCI, but was related to more bleeding.


Synaptic dynamics mediate sensitivity to motion independent of stimulus details.
Humans and other animals generally perceive motion independently of the cues that define the moving object. To understand the underlying mechanisms of this generalization of stimulus attributes, we have examined the cellular properties of avian wide-field tectal neurons that are sensitive to a variety of moving stimuli but not to static stationary stimuli. This in vitro study showed phasic signal transfer at the retinotectal synapse and binary dendritic responses to synaptic inputs that interact in a mutually exclusive manner in the postsynaptic tectal neuron. A model of the tectal circuitry predicts that these two cellular properties mediate sensitivity to a wide range of dynamic spatiotemporal stimuli, including moving stimuli, but not to static stationary stimuli in a tectal neuron. The computation that is independent of stimulus detail is initiated by tectal neurons and is completed by rotundal neurons that integrate outputs from multiple tectal neurons in a directionally selective manner.


Sclerosing lipogranuloma of the male genitalia containing vitamin E: a comparison with classical "paraffinoma".
Sclerosing lipogranuloma of the male genitalia is a rare but distinctive abnormality of the dermis and subcutaneous tissue generally attributed to paraffin injection. We present the results of lipid analysis of lesional tissue from two patients showing the classical clinicopathologic features of this process. No history of local injections could be obtained from either patient. In one case, the patient had applied a vitamin E preparation to the affected area, and tissue lipid analysis demonstrated large quantities of tocopherol and tocopheryl acetate. Analysis of the second case demonstrated a large quantity of tissue paraffin. While this latter patient had applied a topical petrolatum-containing antibiotic preparation to his genital skin, gas-liquid chromatography demonstrated that the paraffins in this preparation differed markedly from the tissue paraffins. No source for this patient's abnormal tissue lipid could be identified.


The effect of FSH on LH induced testosterone secretion in the immature hypophysectomized male rat.
The effect of gonadotropin pretreatment of hypophysectomized male rats on LH stimulated serum testosterone concentrations was studied. A 5 day pretreatment period began 2 days after hypophysectomy at 21 or 24 days of age. On the day following the pretreatment period the animals received an intraperitoneal injection of saline or LH 60 min before blood collection. Animals pretreated with NIH-FSH-B1, or with doses of LH approximating the amount present in the NIH-FSH, had increased testosterone concentrations after LH stimulation compared to similarly stimulated saline pretreated animals. Pretreatment with more highly purified FSH Ex 199C at a lower dose than the minimum effective dose of NIH-FSH was also effective. There was no synergistic or additive effect when FSH Ex 199C and LH pretreatments were combined. FSH Ex 199C is more potent and contains appreciably less LH contamination than NIH-FSH-B1. The results obtained using FSH Ex 199C indicate that FSH, independent of LH contamination, can increase testes response to LH stimulation.


Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats.
Excessive theta (θ) frequency oscillation and synchronization in the basal ganglia (BG) has been reported in elderly parkinsonian patients and animal models of levodopa (L-dopa)-induced dyskinesia (LID), particularly the θ oscillation recorded during periods when L-dopa is withdrawn (the off L-dopa state). To gain insight into processes underlying this activity, we explored the relationship between primary motor cortex (M1) oscillatory activity and BG output in LID. We recorded local field potentials in the substantia nigra pars reticulata (SNr) and M1 of awake, inattentive resting rats before and after L-dopa priming in Sham control, Parkinson disease model, and LID model groups. We found that chronic L-dopa increased θ synchronization and information flow between the SNr and M1 in off L-dopa state LID rats, with a SNr-to-M1 flow directionality. Compared with the on state, θ oscillational activity (θ synchronization and information flow) during the off state were more closely associated with abnormal involuntary movements. Our findings indicate that θ oscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1 θ oscillation may participate in the induction of dyskinesia.


Characterization of cofactor-independent phosphoglycerate mutase isoform-1 (Wb-iPGM) gene: a drug and diagnostic target from human lymphatic filarial parasite, Wuchereria bancrofti.
The inter-conversion of 3-phosphoglycerate and 2-phosphoglycerate during glycolysis and gluconeogenesis in filarial nematodes, is catalyzed by a co-factor-independent phosphoglycerate mutase (iPGM). The gene encoding iPGM isoform-1 was amplified from Wuchereria bancrofti, the major causative agent of human lymphatic filariasis. Partial genomic DNA (gDNA) fragment of the gene was also amplified from periodic and sub-periodic forms of W. bancrofti and Brugia malayi and sequenced. The Wb-iPGM isoform-1 gene encodes an ORF of 515 amino acids and is found to share 99.4%, 96.0%, and 64.0% amino acid sequence identity with iPGM of B. malayi, Onchocerca volvulus, and Caenorhabditis elegans, respectively. Serine and all the other 13 amino acid residues involved in the catalytic function of iPGM are highly conserved. Further comparison of iPGM nucleotide and amino acid sequences of Wolbachia of B. malayi with Wb-iPGM showed 41% and 54.4% similarity, respectively. The analysis of partial genomic and amino acid sequences and phylogenetic tree of Wb-iPGM indicated that this gene, apart from being a potential drug target, could provide diagnostic, taxonomical, and evolutionary markers. This is the first report of the characterization of iPGM gene from W. bancrofti.


Gamma-aminobutyric acid depletion affects stomata closure and drought tolerance of Arabidopsis thaliana.
A rapid accumulation of γ-aminobutyric acid (GABA) during biotic and abiotic stresses is well documented. However, the specificity of the response and the primary role of GABA under such stress conditions are hardly understood. To address these questions, we investigated the response of the GABA-depleted gad1/2 mutant to drought stress. GABA is primarily synthesized from the decarboxylation of glutamate by glutamate decarboxylase (GAD) which exists in five copies in the genome of Arabidopsis thaliana. However, only GAD1 and GAD2 are abundantly expressed, and knockout of these two copies dramatically reduced the GABA content. Phenotypic analysis revealed a reduced shoot growth of the gad1/2 mutant. Furthermore, the gad1/2 mutant was wilted earlier than the wild type following a prolonged drought stress treatment. The early-wilting phenotype was due to an increase in stomata aperture and a defect in stomata closure. The increase in stomata aperture contributed to higher stomatal conductance. The drought oversensitive phenotype of the gad1/2 mutant was reversed by functional complementation that increases GABA level in leaves. The functionally complemented gad1/2 x pop2 triple mutant contained more GABA than the wild type. Our findings suggest that GABA accumulation during drought is a stress-specific response and its accumulation induces the regulation of stomatal opening thereby prevents loss of water.


Prognostic differences between oligometastatic and polymetastatic disease after resection in patients with colorectal cancer and hepatic or lung metastases: Retrospective analysis of a large cohort at a single institution.
Long-term survival data are lacking, and prognostic factors are not well-defined for patients with colorectal cancer and hepatic or lung metastases. This study evaluated the outcomes after resection of oligometastatic hepatic or lung metastases from colorectal cancer and sought to identify prognostic factors. We retrospectively investigated 1,123 patients with colorectal cancer and hepatic or pulmonary metastases who underwent curative surgery between January 1991 and December 2016. Of the 1,123 patients, 719 had hepatic metastases, 287 had pulmonary metastases, and 117 had both. The 5-year overall survival rate was 52.3% in the hepatic metastases group, 70.4% in the pulmonary metastases group, and 71.4% in the hepatic and pulmonary metastases group (P < .001). In total, 1,045 patients had oligometastases (1-5 metastatic lesions in 1 or 2 organs) and 78 had polymetastases (≥6 metastases in 1 or 2 organs). Prognosis was significantly better in patients with oligometastases than in those with polymetastases. The 5-year overall survival rate was 59.0% in the oligometastases group and 35.3% in the polymetastases group (P < .001); the respective 5-year relapse-free survival rates were 37.5% and 11.6% (P < .001). Multivariable analysis identified predictors of both poor overall survival and relapse-free survival to be a high carcinoembryonic antigen level before the first metastasectomy, largest metastasis measuring ≥2 cm, polymetastases, and synchronous metastases. Prognosis after curative resection was better in patients with oligometastatic colorectal cancer in the liver or lung than in those with polymetastases. Multidisciplinary decision-making strategies, including about surgery, should be based on number of metastases rather than their site.


Competition between planar and central chiral control elements in nucleophilic addition to ferrocenyl imine derivatives.
Planar chirality associated with the ferrocene in ferrocenyl oximes and hydrazones bearing chiral auxiliaries effectively competes with or overrides the normally excellent stereocontrol afforded by the auxiliary in determining the diastereoselectivity of addition to the C=N bond.


Serum lipid changes in medical students.
Changes in serum lipids and reasons for these changes were evaluated in 108 medical students, Class of 1975. Serum cholesterol and serum triglycerides were analyzed in their freshman and senior years. A self-administered questionnaire was used to determine if the education in medical school or the knowledge of their freshman lipid vales motivated the students to change their diet and exercise habits. During this four-year period, there was a statistically significant decrease in the mean cholesterol levels (-10 mg. per 100 ml.), while the values increased slightly but not significantly for mean triglyceride (3 mg. per 100 ml.) and weight (2 lb.). Students with abnormal lipid values in their freshman year changed their diets more frequently than those with normal values. When the students were grouped by their change in diet and exercise habits, the largest decrease in lipid values was in those who changed both their diet and exercise. However, the changes in lipid values could not be totally attributed to the students' change in habits. Results suggest that detection and education may contribute to changes in certain risk factors associated with coronary heart disease in young medical students.


Symptomatic versus disease-modifying effects of psychiatric drugs.
Drugs can be divided into two major categories, symptomatic and disease modifying. This review explores whether and how psychiatric drugs fall into one or the other of those categories, and the implications of those results for clinical practice and research in psychopharmacology. Narrative review. Most psychiatric drugs have only short-term effects of improving active symptoms. They do not show long-term benefits for the underlying disease, such as improving the course of illness and improving mortality. Evidence is provided for this claim in the treatment literature of antidepressants for depressive illness and antipsychotics for schizophrenia. Developing truly beneficial drugs for disease modification also is limited by the poor clinical and biological validity of Diagnostic and Statistical Manual diagnoses as well as the use of invalid falsely positive maintenance efficacy randomized discontinuation trial designs. Current psychopharmacology is limited mostly to symptomatic effects, not transformative treatments for the diseases underlying those symptoms. A change in approach is needed in psychopharmacology practice and research, focusing on long-term disease modification rather than short-term symptom improvement.


Data supporting phylogenetic reconstructions of the Neotropical clade Gymnotiformes.
Data is presented in support of model-based total evidence (MBTE) phylogenetic reconstructions of the Neotropical clade of Gymnotiformes "Model-based total evidence phylogeny of Neotropical electric knifefishes (Teleostei, Gymnotiformes)" (Tagliacollo et al., 2016) [1]). The MBTE phylogenies were inferred using a comprehensive dataset comprised of six genes (5277 bp) and 223 morphological characters for an ingroup taxon sample of 120 of 218 valid species and 33 of the 34 extant genera. The data in this article include primer sequences for gene amplification and sequencing, voucher information and GenBank accession numbers, descriptions of morphological characters, morphological synapomorphies for the recognized clades of Gymnotiformes, a supermatrix comprised of concatenated molecular and morphological data, and computer scripts to replicate MBTE inferences. We also included here Maximum-likelihood and Bayesian topologies, which support two main gymnotiform clades: Gymnotidae and Sternopygoidei, the latter comprised of Rhamphichthyoidea (Rhamphichthyidae+Hypopomidae) and Sinusoidea (Sternopygidae+Apteronotidae).


Alternative sites of injection for sentinel lymph node biopsy in breast cancer.
Sentinel node biopsy is rapidly gaining popularity as a less invasive approach to nodal staging in breast cancer. The optimal route of injection of radiocolloids and dye is controversial. The purpose of the present paper was to review and assess the literature. A MEDLINE search for reports of studies involving different injection sites of colloid and/or dye was performed. Although controversial, current evidence suggests that subareolar (SA) or intradermal/subdermal (ID/SD) injection will map the same axillary sentinel nodes (SN) as peritumoral (PT) injection in the vast majority of cases, is at least as successful, and is better logistically. Peritumoral, but not alternative routes, identify extra-axillary sentinel nodes, which are important in a minority of patients. It is recommended that at least some of the radiocolloid be injected peritumorally to avoid missing those SN not located in the ipsilateral axilla. Injection of the dye and a portion of radiocolloid in an ID/SA location is reasonable to take advantage of the general ease and accuracy of ID/SA injections in identifying axillary SN.


Effects of simultaneous and optimized sequential cardiac resynchronization therapy on myocardial oxidative metabolism and efficiency.
Cardiac resynchronization therapy (CRT) can improve left ventricular (LV) hemodynamics and function. Recent data suggest the energy cost of such improvement is favorable. The effects of sequential CRT on myocardial oxidative metabolism (MVO(2)) and efficiency have not been previously assessed. Eight patients with NYHA class III heart failure were studied 196 +/- 180 days after CRT implant. Dynamic [(11)C]acetate positron emission tomography (PET) and echocardiography were performed after 1 hour of: 1) AAI pacing, 2) simultaneous CRT, and 3) sequential CRT. MVO(2) was calculated using the monoexponential clearance rate of [(11)C]acetate (k(mono)). Myocardial efficiency was expressed in terms of the work metabolic index (WMI). P values represent overall significance from repeated measures analysis. Global LV and right ventricular (RV) MVO(2) were not significantly different between pacing modes, but the septal/lateral MVO(2) ratio differed significantly with the change in pacing mode (AAI pacing = 0.696 +/- 0.094 min(-1), simultaneous CRT = 0.975 +/- 0.143 min(-1), and sequential CRT = 0.938 +/- 0.189 min(-1); overall P = 0.001). Stroke volume index (SVI) (AAI pacing = 26.7 +/- 10.4 mL/m(2), simultaneous CRT = 30.6 +/- 11.2 mL/m(2), sequential CRT = 33.5 +/- 12.2 mL/m(2); overall P < 0.001) and WMI (AAI pacing = 3.29 +/- 1.34 mmHg*mL/m(2)*10(6), simultaneous CRT = 4.29 +/- 1.72 mmHg*mL/m(2)*10(6), sequential CRT = 4.79 +/- 1.92 mmHg*mL/m(2)*10(6); overall P = 0.002) also differed between pacing modes. Compared with simultaneous CRT, additional changes in septal/lateral MVO(2), SVI, and WMI with sequential CRT were not statistically significant on post hoc analysis. In this small selected population, CRT increases LV SVI without increasing MVO(2), resulting in improved myocardial efficiency. Additional improvements in LV work, oxidative metabolism, and efficiency from simultaneous to sequential CRT were not significant.


Positive and negative coupling of the endothelin ETA receptor to Ca2+-permeable channels in rabbit cerebral cortex arterioles.
1. Arteriolar segments were isolated from pial membrane and studied within 10 h. Current-clamp and voltage-clamp measurements were made by patch-clamp recording from smooth muscle cells within arterioles. [Ca2+]i was measured from the smooth muscle cell layer by digital imaging of emission from fura-PE3 which was loaded into arterioles by pre-incubation with the acetoxymethyl ester derivative. The external diameter of arterioles was measured using a video-dimension analyser. 2. Endothelin-1 (ET1) was a potent constrictor of isolated arterioles and induced a sustained depolarization up to -27 mV and reduced membrane resistance (EC50 140-170 pm). At a constant holding potential of -60 mV ET-1 induced a transient followed by a sustained inward current. ET1 inhibited L-type voltage-dependent Ca2+ current. 3. ET1 induced a transient followed by sustained elevation of [Ca2+]i. The sustained effect was dependent on extracellular Ca2+. It occurred at a constant holding potential of -60 mV and was not inhibited by the Ca2+ antagonists nicardipine (1 microM) or D600 (10 microM). Thapsigargin (1 microM) completely depleted Ca2+ from caffeine- and ET1-sensitive sarcoplasmic reticulum but did not inhibit the ET1-induced sustained elevation of [Ca2+]i. ET1 effects on [Ca2+]i were prevented by the ETA receptor antagonist BQ123 (cyclo-D-Asp-Pro-D-Val-Leu-D-Trp). 4. The data suggest that ETA receptors are negatively coupled to L-type Ca2+ channels and positively coupled to receptor-operated Ca2+-permeable channels. Inhibition of L-type Ca2+ channel activity may suppress autoregulation, and Ca2+ influx through receptor-operated channels may have a major functional role in the potent long-lasting constrictor effect of endothelin-1 in the cerebral microcirculation.


Treatment of "hernia" in the writings of Celsus (first century AD).
Descriptions concerning "hernia" can be found from the early historical years, and its treatment was a subject mentioned by numerous physicians of Antiquity, such as Hippocrates and Praxagoras of Kos. Yet, Aulus Cornelius Celsus, a famous doctor and encyclopedist of the first century AD, was among the first to propose surgical treatment and carry it out successfully, according to his accounts. Many physicians attempted to treat several types of "hernia" before him, but more "scientific" information with details and complete descriptions could be found only in Celsus' work. In his book De Medicina, Celsus described eight types of "hernia": bronchocele, umbilical hernia, intestinal and omental hernias, hydrocele, varicocele, sarcocele (hernia carnosa), and inguinal hernia. Among them, some retain their ancient nomenclature up to now, although others have acquired gradually different terminology or are not recognized by physicians today as "hernias" (e.g. , bronchocele). For each type of "hernia", Celsus provided his readers with an extremely detailed, well reasoned description of the execution of surgical procedures accompanied usually with pre- and postoperative instructions. His innovations particularly concerned ligature of the vessels. He recommended that an injured vessel be tied in two places with lint threads and then cut between the ties. Other pre- and postoperative practices, such as sterilization and bandaging of the incised area, were elements that helped in the advances of medicine, and some of them still exist in modern medicine.


Delay of gratification in obese children.
Obese (n = 20) and normal weight (n = 20) children (8-11 years) were compared using the delay of gratification paradigm. All children were asked to choose between an immediate reward or a larger delayed (one day) reward. Half the children were offered an edible incentive and half a non-edible incentive. Results showed that the obese choose immediate rewards more often than normals only when the incentive was edible. This suggests that deficits in delay of gratification shown by obese children are not generalized dispositions but are specific to food. A second aspect of the study examined preference for food vs non-food items and activities. Normals showed a much stronger preference for non-food items, nutritious foods and non-food related activities than the obese. This suggests that the deficits in delay of gratification shown by the obese children for food related items may be due to the stronger incentive value of these items for them.


Influence of single and double immunomagnetic depletion on the hemopoietic capacity of marrow in patients with advanced neuroblastoma submitted to autologous bone marrow transplantation.
Eighteen marrows from 16 patients with advanced neuroblastoma were submitted to a single or double immunomagnetic depletion procedure to purge them of tumor cells. Analysis of results showed that the CFU-GM recoveries were 59% +/- 16 (SE) and 33% +/- 16 after one or two cycles of incubation with microspheres. This led to yields of 7.8 x 10(4) and 4.1 x 10(4) CFU-GM available per kg body weight, respectively. Successful engraftment was demonstrated in all evaluable patients. However, some patients had delayed hematologic recoveries, particularly for platelets.


N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-κB pathways.
Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.


Antagonism of BMP signaling is insufficient to induce fibrous differentiation in primary sclerotome.
Sclerotome is the embryonic progenitor of the axial skeleton. It was previously shown that Tgfbr2 is required in sclerotome for differentiation of fibrous skeletal tissues including the annulus fibrosus of the intervertebral disc. Alternatively, BMP signaling is required to form the vertebral body through chondrogenesis. In addition, TGFβ added to sclerotome cultures induces expression of markers for fibrous tissue differentiation but not cartilage or bone. The mechanism of how TGFβ signaling regulates this lineage decision in sclerotome is not known and could be due to the production of instructive or inhibitory signals or a combination of the two. Here we show that TGFβ antagonizes BMP/ Smad1/5 signaling in primary sclerotome likely through regulation of Noggin, an extracellular BMP antagonist, to prevent chondrogenesis. We then tested whether inhibition of BMP signaling, and inhibition of chondrogenesis, is sufficient to push cells toward the fibrous cell fate. While Noggin inhibited BMP/ Smad1/5 signaling and the formation of chondrogenic nodules in sclerotome cultures; Noggin and inhibition of BMP signaling through Gremlin or DMH2 were insufficient to induce fibrous tissue differentiation. The results suggest inhibition of BMP signaling is not sufficient to stimulate fibrous tissue differentiation and additional signals are likely required. We propose that TGFβ has a dual role in regulating sclerotome fate. First, it inhibits BMP signaling potentially through Noggin to prevent chondrogenesis and, second, it provides an unknown instructive signal to promote fibrous tissue differentiation in sclerotome. The results have implications for the design of stem cell-based therapies for skeletal diseases.


The global health workforce shortage: role of surgeons and other providers.
The debate over the status of the physician workforce seems to be concluded. It now is clear that a shortage of physicians exists and is likely to worsen. In retrospect it seems obvious that a static annual production of physicians, coupled with a population growth of 25 million persons each decade, would result in a progressively lower physician to population ratio. Moreover, Cooper has demonstrated convincingly that the robust economy of the past 50 years correlates with demand for physician services. The aging physician workforce is an additional problem: one third of physicians are over 55 years of age, and the population over the age of 65 years is expected to double by 2030. Signs of a physician and surgeon shortage are becoming apparent. The largest organization of physicians in the world (119,000 members), the American College of Physicians, published a white paper in 2006 titled, "The Impending Collapse of Primary Care Medicine and Its Implications for the State of the Nation's Health Care" [37]. The American College of Surgeons, the largest organization of surgeons, has published an article on access to emergency surgery [38], and the Institute of Medicine of the National Academies of Science has published a book on the future of emergency care (Fig. 10). The reports document diminished involvement and availability of emergency care by general surgeons, neurologic surgeons, orthopedists, hand surgeons, plastic surgeons, and others. The emergency room has become the primary care physician after 5 PM for much of the population. A survey done by the Commonwealth Fund revealed that less than half of primary care practices have an on-call arrangement for after-hours care. Other evidence of evolving shortage are reports of long wait times for appointments, the hospitalist movement, and others. The policies for the future should move beyond dispute over whether or not a shortage exists. The immediate need is for the United States, as a society, to commit to workforce self sufficiency in health care. The reliance on international graduates for more than 25% of the nation's physicians is a transnational problem. Reliance on IMGs, nurses and other health professions for the United States workforce is an issue of international distributive justice. Wealthy, developed countries, such as the United States, should be able to educate sufficient health professionals without relying on a less fortunate country's educated health workers. The 2000 Report of the Chair of the AAMC, the accrediting agency for United States and Canadian medical schools through the LCME, recommended expansion of medical school class sizes and expansion of medical schools [41]. For the past 25 years, the AAMC has supported a no-growth policy and the goal that 50% of USMGs be primary care physicians. In 2003, the AAMC developed a workforce center,-led by Edward Salsberg. The workforce center has provided valuable data and monitoring of the evolving workforce graduating from medical and and osteopathic schools in the United States. The NRMP, also managed by the AAMC, has begun useful studies analyzing the specialty choices of the more than 20,000 participants in the Match each year. The AAMC workforce policy was altered in 2006, and a 12-point policy statement was issued (see http://aamc.workforceposition.pdf). Three of the 12 points reflected significant change from past positions. They are a call for a 30% increase in physicians graduated by United States allopathic medical schools and an increase in residency positions now limited by the BBA of 1997. The recommendation that students make personal specialty choices reversed the prior recommendation that a majority of students enter primary care practice.


Twiddler's syndrome after dorsal root ganglion stimulation: A case report.
Dorsal root ganglion stimulation (DRG-S) is a promising therapy for chronic neuropathic pain, but complications of this therapy are poorly understood. Twiddler's syndrome, a rare complication characterized by lead displacement and coiling of wires, has been reported in other neuromodulation devices, but has not been described in the context of DRG-S. Here, we present a first-of-a-kind case report of Twiddler's syndrome occurring after 8 months of DRG-S. This case report highlights the importance of considering Twiddler's syndrome as a potential complication in patients undergoing DRG-S, especially in those with significant weight loss history.


Quantitative analysis of the number and distribution of neurons richly innervated by GABA-immunoreactive axons in the rat superior cervical ganglion.
The superior cervical ganglion of rats contains a considerable number of nerve fibers with GABA-like immunoreactivity which show a nonuniform distribution within the ganglion. The topography of these fibers has been analyzed by using antibodies raised against GABA-BSA-glutaraldehyde complexes. GABA-positive axons and axon varicosities accumulated around a subpopulation of principal ganglion cells forming basketlike patterns. These neurons richly innervated by GABA-positive axons (RIG-neurons) in turn were aggregated in patches with strong immunoreactivity. The size and packing density of the patches containing RIG-neurons and GABA-positive axons approaching them had rostral-to-caudal and medial-to-lateral gradients. Similar patterns were found in right and left ganglia. In five ganglia, a quantitative analysis revealed on average 1,344 RIG-neurons per ganglion representing about 5% of the total neuron population, with small variations (standard deviation 122) despite the highly variable shape of the ganglia. The distribution of RIG-neurons resembles that of neurons sending their axons into the internal carotid nerve. To check this possible correlation, HRP was injected into the eye and applied to the transected external carotid nerve. Double staining for the retrogradely transported peroxidase and GABA immunohistochemistry revealed that RIG-neurons formed a small subpopulation of retrogradely labelled neurons in both experiments. This suggests that RIG-neurons innervate various target organs. This conclusion is in agreement with the observation that RIG-neurons also exist in other sympathetic ganglia. Data presented suggest that sympathetic ganglion cells can be classified on the basis of non-uniform innervation patterns formed by axons that use different neurotransmitters.


Modeling Parkinson's Disease Heterogeneity to Accelerate Precision Medicine.
A mechanistic understanding of the diverse clinical manifestations of Parkinson's disease (PD) and variable patient response to treatments is lacking. Genetically diverse PD model organisms can be used to map modifier genes and understand clinically relevant phenotypes of varying severity. This strategy can accelerate the pace of discoveries for precision medicine purposes.


Dietary protein and experimental carcinogenesis.
This review summarizes selected information about the influence of proteins, protein-fat interactions, and calorie intake on carcinogenesis. Most of the definitive studies concerning protein and cancer have utilized protein underfeeding and feed restriction. Optimal or less than optimal protein intakes have generally inhibited spontaneous and chemically induced tumor growth as well as the growth of transplantable tumors. Studies have focused on the quantity of protein and its amino acid supply rather than its source. Raising protein intake increases carcinogen metabolizing capacity, and the incidence of tumors depends upon the biologic activity of the metabolites that are formed. The few published studies dealing with the effects of protein on chemically induced colon, mammary, and liver cancers show that the incidence varied with the carcinogen and the level of protein fed at the time of carcinogen administration. With 1,2-dimethylhydrazine, a colon cancer-inducing agent, the toxic and tumorigenic responses have varied with the route of administration, the level of protein fed, and the level and duration of exposure to the carcinogen. In some instances, high protein diets may have led to a lower incidence of tumors because of depressed feed intake, a known confounding factor. The existing data about the relation of protein to cancer make generalizations about mechanisms hazardous because experimental models and protocols have varied widely. Some early studies undoubtedly used diets that lacked nutrients now known to be essential. Unfortunately, some recent studies have overlooked established nutritional principles and the known nutritional requirements appropriate for the age and species of animals used as models.


Elevated intracellular pH of zygotes during mouse aging causes mitochondrial dysfunction associated with poor embryo development.
The mortality of preimplantation embryos is positively correlated with maternal age. However, the underlying mechanism for the poor quality of embryos remains unclear. Here, we found that aging caused elevated intracellular pH (pHi) in zygotes, which could trigger aberrant mitochondrial membrane potential, increased reactive oxygen species (ROS) levels, and poor embryo development. Moreover, single-cell transcriptome sequencing of mouse zygotes identified 120 genes that were significantly differentially expressed (DE) between young and older zygotes. These include genes such as Slc14a1, Fxyd5, CD74, and Bst, which are related to cell division, ion transporter, and cell differentiation. Further analysis indicated that these DE genes were enriched in apoptosis, the NF-kappa B signaling pathway, and the chemokine signaling pathway, which might be the key regulatory pathway affecting the quality of zygotes and subsequent embryo development. Taken together, our study helps elucidate the poor quality and development of older preimplantation embryos.


Predictive modelling of growth and measurement of enzymatic synthesis and activity by a cocktail of selected Enterobacteriaceae and Aeromonas hydrophila.
The possibility was examined of developing a predictive model that would predict food spoilage by combining microbial growth (increase in cellular number) with extracellular enzymatic activity of a cocktail of five strains of Enterobacteriaceae: Escherichia coli, Enterobacter agglomerans, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus vulgaris and one Aeromonas hydrophila strain. Estimations of growth and enzyme activity were made within a three-dimensional matrix of conditions: temperature 2-20 degrees C, pH value 4.0-7.5 and water activity (a(w)) 0.95-0.995. A mathematical model was constructed which predicted growth based on increases in cell number. However, although notable effects of extracellular lipases and proteases were detected, it was not possible to model enzymatic activity and prepare a combined model because the data did not follow the characteristic profile that would allow curve-fitting. Nevertheless, the model for microbial growth and information relating to enzyme activity will be made freely available in a database on the internet.


Simultaneous determination of nitrendipine and hydrochlorothiazide in spontaneously hypertensive rat plasma using HPLC with on-line solid-phase extraction.
A HPLC method with on-line solid phase extraction (SPE) and DAD detection was developed for the simultaneous determination of nitrendipine and hydrochlorothiazide in spontaneously hypertensive rat (SHR) plasma. Plasma samples (100 μL) were injected directly onto a CAPCELL MF C(8) SPE column. High-abundance proteins and most matrixes in plasma were removed by on-line SPE technology, while nitrendipine and hydrochlorothiazide trapped on the SPE column were effectively separated on a C(18) analytical column. The column temperature was maintained at 20°C. The optimal detection wavelength was 237 nm for NTDP and 271 nm for HCTZ. The total analytical run time was 34 min. The proposed method was linear over the range 5-500 ng mL(-1) for nitrendipine and 10-1000 ng mL(-1) for hydrochlorothiazide. The lower limit of detection (LLOD) was 0.5 and 0.6 ng mL(-1) for nitrendipine and hydrochlorothiazide, respectively. The sensitivity and precision of the method were within acceptable limits during validation period. The method was successfully used to investigate the pharmacokinetic characteristics of nitrendipine and hydrochlorothiazide in spontaneously hypertensive rats.


Association of mitochondrial haplogroup J and mtDNA oxidative damage in two different North Spain elderly populations.
This work investigates the association between longevity, mitochondrial DNA (mtDNA) variants and oxidative DNA damage in an older than 85 years population. The participants, similar in genetic and cultural background as well as gender distribution, come from villages near to the Pyrenees Mountains (900-1,400 m altitude) (n = 69) and the Ebro's Valley (200-300 m altitude) (n = 69) in Spain. Our results show an accumulation of the haplogroup J in elderly individuals with an over-representation of J2 in Pyrenees group but not in the Ebro's Valley, the former associating with a diminished DNA damage. In conclusion, our results suggest that J mitochondrial variant, that induce lower mtDNA damage, could present a phenotypic survival advantage to environmental conditions and, thus, accumulate in elderly population.


Continuous quality improvement: reducing informed consent form signing errors.
Adherence to ethical guidelines and regulations and protecting and respecting the dignity and autonomy of participants by obtaining a valid informed consent form (ICF) prior to participation in research are crucial; The subjects did not add signatures next to the corrections made to signatures or dates on the ICF, Multiple signatures in other fields, ICF missing/missing signature, Incorrect ICF version Signed after modification, Correction tape used to correct signature, Impersonated signature, Non-research-member signature, however, ICFs are often not properly completed, which must be addressed. This study analyzed ICF signing errors and implemented measures to reduce or prevent these errors. We used the plan-do-check-act (PDCA) cycle to help improve the correctness and validity of ICF signing. Interim and final reports from January 2016 to February 2020 including 363 ICFs were studied. The total proportion of correct ICF signatures (200, 83.3%) following the PDCA intervention was significantly higher than that before the intervention (P < 0.05). Analysis of the types of signing error demonstrated that signature errors were significantly reduced after the intervention, particularly for subjects did not add signatures next to the corrections made to signatures or dates on the ICF (16, 6.7%) and impersonated signature (0; P < 0.05). The proportions of other error types-multiple signatures in other fields, missing or unsigned ICF, incorrect signature order, incorrect ICF version, use of correction tape to correct signature, and non-medical profession members signing the ICF-did not differ significantly.


Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma: Hemodynamic Management.
Does the active maintenance of arterial blood pressure after injury affect clinical outcomes in patients with thoracic and lumbar fractures? There is insufficient evidence to recommend for or against the use of active maintenance of arterial blood pressure after thoracolumbar spinal cord injury. Grade of Recommendation: Grade Insufficient However, in light of published data from pooled (cervical and thoracolumbar) spinal cord injury patient populations, clinicians may choose to maintain mean arterial blood pressures >85 mm Hg in an attempt to improve neurological outcomes. Consensus Statement by the Workgroup The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_6.


Interaction of the -170 cyclic AMP response element with the adjacent CCAAT box in the human fibronectin gene promoter.
In the fibronectin gene promoter the cAMP response element (CRE) and the CCAAT box are separated by only 20 base pairs (bp), i.e. two turns of double helix. Binding of nuclear proteins to these elements, assessed by DNase I footprinting, differs in the different cell types. While in a variety of cells tested (HeLa, granulosa, brain, and adenocarcinoma) only CRE binding activity is observed, liver extracts show both CRE and CCAAT binding activities. Competitions with CRE oligonucleotides were able to prevent the binding of both liver factors, while competitions with CCAAT oligonucleotides only abolished the binding to the CCAAT box. Consistently, the occupation of the CCAAT box was reduced when the distance between the CRE and CCAAT elements was increased in a series of spacing mutants in which DNA fragments of 20, 28, or 44 bp were inserted, and in a construct where the CRE sequence was deleted. Furthermore, the mutants are less efficient than the wild type as templates for in vitro transcription elicited by liver nuclear extracts. Transcriptional activity decreases with the 20- and 28-bp insertions but is partially recovered with the 44-bp insertion. Partial purification of liver CRE- and CCAAT-binding proteins by high performance liquid chromatography on a Mono Q column and recombination of column fractions showed that a novel 73-kDa CRE-binding protein facilitates the association of the CCAAT-binding protein to the CCAAT site of the fibronectin gene.


Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex.
Formation of synapses requires specific cellular interactions that organize pre- and postsynaptic compartments. The neuroligin-neurexin complex mediates heterophilic adhesion and can trigger assembly of glutamatergic and GABAergic synapses in cultured hippocampal neurons. Both neuroligins and neurexins are encoded by multiple genes. Alternative splicing generates large numbers of isoforms, which may engage in selective axo-dendritic interactions. We explored whether alternative splicing of the postsynaptic neuroligins modifies their activity toward glutamatergic and GABAergic axons. We find that small extracellular splice insertions restrict the function of neuroligin-1 and -2 to glutamatergic and GABAergic contacts and alter interaction with presynaptic neurexins. The neuroligin isoforms associated with GABAergic contacts bind to neurexin-1alpha and a subset of neurexin-1betas. In turn, these neurexin isoforms induce GABAergic but not glutamatergic postsynaptic differentiation. Our findings suggest that alternative splicing plays a central role in regulating selective extracellular interactions through the neuroligin-neurexin complex at glutamatergic and GABAergic synapses.


Enthalpies of formation from B3LYP calculations.
We have calculated the geometries, energies, and normal vibrations of 845 compounds containing the elements H, C, N, O, F, Al, Si, P, S, and Cl using hybrid density functional theory in order to investigate the accuracy of atom-additive schemes for predicting enthalpies of formation at 298 K. The results give a more realistic estimate of the accuracy of density functional calculations than some overoptimistic earlier correlations. We have also calculated atom-additive schemes for the zero-point energies and enthalpic corrections to the energies. Remarkably, it is not important to include the vibrational or rotational contributions, which can be estimated well within a purely Born-Oppenheimer regression model.


Zeolite micropattern for biological applications.
A facile method was established using composition-gradient pattern on zeolite surface to guide the deposition and formation of chemical and biomolecular patterns with features as small as five microns.


Hypertensive emergencies of pregnancy.
Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.


Kainic acid inhibits cholecystokinin release from rat hippocampal slices.
Antagonistic interactions between cholecystokinin (CCK) and nanomolar concentrations of kainic acid (KA) have been reported in area CA3 of the rat hippocampal slice. This study tested the possibility that kainic acid inhibits the release of CCK. Elevated K+ was found to release CCK from hippocampal slices in a Ca2+-dependent manner. KA, at concentrations as low as 100 nM, inhibited this release by about one-third. Because CCK appears to exert a net inhibitory effect on the firing of CA3 pyramidal cells, the epileptogenic action of KA may be explained, in part, by the depression of CCK release.


Survival, causes of death, and the prognostic role of comorbidities in chronic lymphocytic leukemia in the pre-ibrutinib era: A population-based study.
To evaluate temporal trends in survival and causes of death in patients with chronic lymphocytic leukemia (CLL) in a nationwide study. The cohort consisted of 13,009 Swedish CLL patients diagnosed 1982-2013. Relative survival (RS) and excess mortality rate ratios (EMRR) with 95% confidence intervals (95% CIs) were estimated using flexible parametric survival models. Cause-specific hazard ratios (HRs) were estimated for the linear effect of 10-year increase in year of diagnosis. The excess mortality decreased comparing 2003-2013 to 1982-1992 (EMRR = 0.53, 95% CI 0.48-0.58). The 5-year RS increased between 1982 and 2012 for patients >51 years at diagnosis and improved for patients ≤51 years after 2002. The rate of CLL-specific deaths decreased over time (HR = 0.78, 95% CI 0.75-0.81). Compared to patients with no comorbidity, patients with 1 and 2+ Charlson Comorbidity Index points had HR = 1.35 (95% CI 1.25-1.45) and HR = 1.47 (95% CI 1.37-1.57) for CLL-related mortality, respectively. Survival in CLL patients improved in the era of chemoimmunotherapy, and this was largely explained by reduced CLL-related mortality. The increased rate of CLL-related mortality in patients with comorbidities emphasizes the importance of the newer and better tolerated targeted therapy.


Electrohydrodynamic atomization for biodegradable polymeric particle production.
Electrohydrodynamic atomization (EHDA) has many applications such as electrospray ionization in mass spectroscopy, electrospray deposition of thin films, pharmaceutical productions, and polymeric particle fabrications for drug encapsulation. In the present study, EHDA was employed to produce biodegradable polymeric micro- and nanoparticles. The effects of processing parameters such as polymer concentration, flow rate, surfactants, organic salt, and setup configurations on the size and morphology of polymeric particles were investigated systematically. By changing the various processing parameters, controllable particle shape and size can be achieved. PLGA nanoparticles with size of around 250 nm can be obtained by using organic salts to increase the conductivity of the spraying solution even at a relatively high flow rate. A higher flow rate has the advantage of producing a stable cone spray and can be easily reproduced. Solid and porous particles can be fabricated using different experimental setups to control the organic solvent evaporation rate. Also, paclitaxel, a model antineoplastic drug, was encapsulated in polymeric particles which can be employed for controlled release applications. In short, EHDA is a promising technique to fabricate polymeric micro- or nanoparticles which can be used in drug delivery systems.


New 1,2,3-triazole derivatives (ureas, amides, urethanes) with a potential biological interest.
This paper reports the preparation of three series of 1,2,3-triazole derivatives bearing an ureido substituent (compounds 5a-h), a carboxamido substituent (compounds 6a-f) or an urethane substituent (compounds 7a-l). Some compounds were submitted to in vitro functional tests on guinea-pig isolated intestinal preparations and/or to in vitro antitumor and antiviral screening. The tested compounds showed no activity on guinea-pig ileum, except compound 7g, provided of contracturant properties; similarly, no anticancer or antiviral significant activity was found.


Cerebrovascular Reactivity Mapping Using Resting-State Functional MRI in Patients With Gliomas.
Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases. To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas. Retrospective. Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas. Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T scanner. rs-CVR with various frequency ranges and resting-state fluctuation amplitude (RSFA) were assessed. The agreement between each rs-based CVR measurement and bh-CVR was determined by voxel-wise correlation and Dice coefficient in the whole brain, gray matter, and the lesion region of interest (ROI). Voxel-wise Pearson correlation, Dice coefficient, Fisher Z-transformation, repeated-measure analysis of variance and post hoc test with Bonferroni correction, and nonparametric repeated-measure Friedman test and post hoc test with Bonferroni correction were used. Significance was set at P < 0.05. Compared with bh-CVR, the highest correlations were found at the frequency bands of 0.04-0.08 Hz and 0.02-0.04 Hz for rs-CVR in both whole brain and the lesion ROI. RSFA had significantly lower correlations than did rs-CVR of 0.02-0.04 Hz and a wider frequency range (0-0.1164 Hz). Significantly higher correlations and Dice coefficient were found in normal tissues than in the lesion ROI for all three methods. The optimal frequency ranges for rs-CVR are determined by comparing with bh-CVR in patients with gliomas. The rs-CVR method outperformed the RSFA. Significantly higher correlation and Dice coefficient between rs- and bh-CVR were found in normal tissue than in the lesion. 3 TECHNICAL EFFICACY STAGE: 2.


Deuterated phospholipids as Raman spectroscopic probes of membrane structure. Phase diagrams for the dipalmitoyl phosphatidylcholine(and its d62 derivative)-dipalmitoyl phosphatidylethanolamine system.
Raman spectroscopic techniques have been used to construct phase diagrams for the binary phospholipid systems, DPPC-d62/DPPE and DPPC/DPPE (DPPC, dipalmitoyl phosphatidylcholine; DPPE, dipalmitoyl phosphatidylethanolamine). For the former, the half-width of the C-2H stretching modes of the deuterated component near 2100 cm-1 serves as an indicator of phospholipids fluidity. The phase behavior is described semi-quantitatively using regular solution theory with the following non-ideality parameters: rho(1)0 = 0.75 kcal/mol and rho(s)0 = 1.05 kcal/mol. The use of deuterated phospholipids as one component of a binary mixture permits direct evaluation of the conformation of a particular component in the mixture throughout the phase separation region. The approach is demonstrated with the help of a simple model correlating the half-width of the symmetric C-2H stretching mode with the fraction of DPPC-d62 hydrocarbon chains in the liquid crystalline state. The effect of chain perdeuteration on the phase behavior of DPPC with DPPE is evaluated by comparison of the phase diagram of the DPPC-d62/DPPE system with that of DPPC-DPPE. The latter has been constructed previously from both probe and calorimetric techniques, and is created from the Raman spectroscopic data using the I(1130/1100) ratio to characterize the transgauche population ratio in non-deuterated hydrocarbon chains. A reasonable fit to the phase behavior is obtained using: rho(1)0 = 0.85 kcal/mol and rho(s)0 = 0.90 kcal/mol. The similarities of the non-ideality parameters in the two phase diagrams indicate that the effect of perdeuteration on the phase behavior of DPPC is not extensive. The use of deuterated phospholipids as essentially unperturbed components of a model membrane system is justified.