Significant Enhancement of Thermoelectric Properties of PTB7 Conducting Polymer by Mixed-Solvent Approach.
The thermoelectric properties of poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}), commonly known as PTB7 conducting polymer, were investigated for the first time by Rastegaralam et al. in 2017 [ Crystals 2017, 7, 292]. PTB7 showed higher electrical conductivity or Seebeck coefficient (or even both) and, hence, a higher thermoelectric power factor than a variety of organic semiconductors. Therefore, it is worth working more on this semiconductor to improve its thermoelectric figure of merit. In this work, for the first time the effect of cosolvents on the thermoelectric properties of PTB7 is investigated. PTB7 conducting polymer dissolved in chlorobenzene was treated with different solvents: N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), acetonitrile (AC), and 1,2-dichloroethane (DCE). Upon addition of DMF, DMSO, and NMP, a significant enhancement in the electrical conductivity of the samples accompanied by a reduction in the Seebeck coefficient occurred as a result of doping, while the use of AC and DCE led to simultaneous enhancement in the electrical conductivity and the Seebeck coefficient by increasing the mobility. The dopants used in this work are inexpensive, are easily available, and do not need to perform any synthesis process. The highest estimated figure of merit value obtained in this work without optimization is 0.1, which is of the highest values for organic thermoelectric materials.


Pharmaceutical aspects of salt and cocrystal forms of APIs and characterization challenges.
In recent years many efforts have been devoted to the screening and the study of new solid-state forms of old active pharmaceutical ingredients (APIs) with salification or co-crystallization processes, thus modulating final properties without changing the pharmacological nature. Salts, hydrates/solvates, and cocrystals are the common solid-state forms employed. They offer the intriguing possibility of exploring different pharmaceutical properties for a single API in the quest of enhancing the final drug product. New synthetic strategies and advanced characterization techniques have been recently proposed in this hot topic for pharmaceutical companies. This paper reviews the recent progresses in the field particularly focusing on the characterization challenges encountered when the nature of the solid-state form must be determined. The aim of this article is to offer the state-of-the-art on this subject in order to develop new insights and to promote cooperative efforts in the fascinating field of API salt and cocrystal forms.


Sedimentation properties of rat liver mitochondria. Effects of cortisone treatment.
A prediction of the velocity of sedimentation of rat liver mitochondria in sucrose gradients is made on the basis of recent measurements of the size of isolated mitochondria suspended in sucrose medium and the model proposed by Bentzel and Solomon to describe the osmotic behavior of mitochondria. The experimentally observed velocity is extremely close to the predicted value and confirms by a different approach the estimate of mitochondrial volume made by Baudhuin and Berthet on the basis of electron microscopic measurements. Because cortisone treatment of rats is known to result in a marked increase in mitochondrial size as observed under the electron microscope, mitochondria were co-isolated from livers of control and cortisone-treated animals, and the sedimentation behavior of the mixtures was examined by sucrose density gradient centrifugation. Mitochondria from cortisone-treated animals were found to sediment 1.4 times as rapidly as those from control animals, indicating that their increased size cannot entirely be due to an increased imbibition of fluid from the surrounding sucrose medium, and that the change in size must at least in part be due to a change in content of nondiffusible mitochondrial components. Although the increase in sedimentation velocity of mitochondria from cortisone-treated animals is striking, it is less than that predicted solely on the basis of their size relative to that of control mitochondria. It is concluded that the increases in mitochondrial size and content of nondiffusible components produced by cortisone treatment are accompanied by alterations in mitochondrial composition as well.


Core temperature and heart rate response to repeated bouts of firefighting activities.
During live-fire firefighting operations and training evolutions, firefighters often consume multiple cylinders of air and continue to wear their personal protective equipment even after fire suppression activities have ceased. However, most studies have only reported core temperature changes during short-term firefighting activities and have shown a very modest increase in core temperature. Therefore, the purpose of this study is to evaluate core temperature and heart rate (HR) during repeated bouts of firefighting activity over ∼3 h. The results of this study show that core temperatures increase by an average of 1.9°C--to a larger magnitude than previously reported--and continue to increase during subsequent work cycles (38.4 vs. 38.7) even after long breaks of more than 30 min. The rate of core temperature increase during work continues to increase later in the training exercise (from 0.036 to 0.048°C/min), increasing the risk for exertional heat stress particularly if long-duration firefighting activity is required at these later times. To date, core temperature and HR changes during firefighting have been reported for short-term studies, which may significantly underestimate the physiological burden of typical firefighting activities. Firefighter core temperatures are shown to increase to a larger magnitude than previously observed and the rate of rise in core temperature increases during subsequent firefighting activities.


Orthogonal chain collapse in stimuli-responsive di-block polymers leading to self-sorted nanostructures.
We design amphiphilic di-block copolymers (P-b-F and P-b-C) tethered with stimuli-responsive ferrocene and coumarin hydrophobic pendants that exhibit chain collapse behaviour in response to light, redox and chemical cues, with subsequent transformation of the vesicles into micelles. Interestingly, the co-assembled vesicles of the polymer blend under orthogonal stimuli furnish self-sorted micelles and vesicles.


Characterization of a hybrid hamster-human cell line complemented for the ataxia telangiectasia DNA repair defects.
The fibroblast cell line AT5BIVA, from ataxia telangiectasia complementation group D, was transfected with a neo gene providing G418 resistance for subsequent selections. The G418 resistant cell line was fused with gamma-irradiated Chinese hamster ovary cells and a radioresistant hybrid, atxbc, was isolated following an X-ray selection procedure. All the cellular defects characteristic of ataxia telangiectasia were corrected to some degree; atxbc cells: (i) were confirmed to be resistant to X-rays; (ii) had regained control over DNA synthesis after DNA damage, and (iii) could overcome the radiation-induced block in the G2 phase of the cell cycle. Repetitive element polymerase chain reaction amplification of integrated hamster DNA from primers to middle repetitive elements confirmed the presence of hamster-specific sequences, suggesting that the phenotype of the cells had been corrected by integration of a normal hamster gene rather than by a reversion event.


Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics.
Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsisthaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica). The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST), hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.


Evolution of the Pathology Residency Curriculum: Preparing for a Positive Future.
The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology-where we have been, what our actual current training curriculum is now-to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s). To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1) reflect upon what are the critical need subjects, (2) identify areas that have become of lesser importance, and then (3) prioritize training accordingly.


The effect of an endogenous antioxidant glabridin on oxidized LDL.
Oxidative stress is thought to play a central role in low-density lipoprotein (LDL) oxidation, and the oxidative modification of LDL is thought to be a key factor during early atherogenesis. Therefore, the prevention of LDL oxidation by antioxidants might arrest the progression of atherosclerosis. This study was conducted to determine the effect of glabridin, a natural polyphenolic isoflavone antioxidant isolated from licorice root, on LDL oxidation. The determination of the extent of LDL oxidation was accomplished by measuring the formation of thiobarbituric acid reactive substances (TBARS). The oxidative stress level was assessed using a FORM system/CR 3000 instrument. After the oral administration of a glycyrrhizin-free licorice-root methanol extract (containing glabridin 60 mg) to healthy subjects for 6 months, the subjects' oxidative stress level as well as plasma LDL oxidation decreased by 20%. We conclude that the dietary consumption of glabridin can partially protect LDL from oxidation.


Central pancreatectomy: the Dagradi Serio Iacono operation. Evolution of a surgical technique from the pioneers to the robotic approach.
Central pancreatectomy (CP) is a parenchyma-sparing surgical procedure. The aims are to clarify the history and the development of CP and to give credits to those from whom it came. Ehrhardt, in 1908, described segmental neck resection (SNR) followed, in 1910, by Finney without reconstructive part. In 1950 Honjyo described two cases of SNR combined with gastrectomy for gastric cancer infiltrating the neck of the pancreas. Guillemin and Bessot (1957) and Letton and Wilson (1959) dealt only with the reconstructive aspect of CP. Dagradi and Serio, in 1982, performed the first CP including the resective and reconstructive aspects. Subsequently Iacono has validated it with functional endocrine and exocrine tests and popularized it worldwide. In 2003, Baca and Bokan performed laparoscopic CP and, In 2004, Giulianotti et al performed a robotic assisted CP. CP is performed worldwide either by open surgery or by using minimally-invasive or robotic approaches. This confirms that the operation does not belong to whom introduced it but to everyone who carries out it; however credit must be given to those from whom it came.


Time-Domain Line-Shape Analysis from 2D Spectroscopy to Precisely Determine Hamiltonian Parameters for a Photosynthetic Complex.
Optical signals come from coherences between quantum states, with spectral line widths determined by the coherences' dephasing dynamics. Using a 2D electronic spectrometer, we observe weak coherence- and rephasing-time-domain signals persisting to 1 ps in the Fenna-Matthews-Olson complex at 77 K. These are coherences between the ground and excited states prepared after the complex interacts once or three times with light, rather than zero-quantum coherences that are more frequently investigated following two interactions. Here, we use these small but persistent signal components to isolate spectral contributions with narrowed peaks and reveal the system's eigenenergies.


Distinct Features of Human Myeloid Cell Cytokine Response Profiles Identify Neutrophil Activation by Cytokines as a Prognostic Feature during Tuberculosis and Cancer.
Myeloid cells are a vital component of innate immunity and comprise monocytes, macrophages, dendritic cells, and granulocytes. How myeloid cell lineage affects activation states in response to cytokines remains poorly understood. The cytokine environment and cellular infiltrate during an inflammatory response may contain prognostic features that predict disease outcome. In this study, we analyzed the transcriptional responses of human monocytes, macrophages, dendritic cells, and neutrophils in response to stimulation by IFN-γ, IFN-β, IFN-λ, IL-4, IL-13, and IL-10 cytokines to better understand the heterogeneity of activation states in inflammatory conditions. This generated a myeloid cell-cytokine-specific response matrix that can infer representation of myeloid cells and the cytokine environment they encounter during infection, in tumors and in whole blood. Neutrophils were highly responsive to type 1 and type 2 cytokine stimulation but did not respond to IL-10. We identified transcripts specific to IFN-β stimulation, whereas other IFN signature genes were upregulated by both IFN-γ and IFN-β. When we used our matrix to deconvolute blood profiles from tuberculosis patients, the IFN-β-specific neutrophil signature was reduced in tuberculosis patients with active disease, whereas the shared response to IFN-γ and IFN-β in neutrophils was increased. When applied to glioma patients, transcripts of neutrophils exposed to IL-4/IL-13 and monocyte responses to IFN-γ or IFN-β emerged as opposing predictors of patient survival. Hence, by dissecting how different myeloid cells respond to cytokine activation, we can delineate biological roles for myeloid cells in different cytokine environments during disease processes, especially during infection and tumor progression.


[Preventive-curative dental care in a large East German urban population. The 4-year experiences of a Dresden prevention study with 16- to 35-year-old subjects].
The present 4-year Dresden preventive study was carried out to realize a dental care concept with preventive emphasis in 6 Dresden state health services. 2502 patients aged 16-35 years were randomly selected in 1988. The effectiveness of this study was evaluated by means of the parameters oral health behaviour, oral health state and preventive care needs. The spectrum of methods included extended anamnesis, plaque index according to Silness & Löe, DMF/T, DMF/S, GPM/T index, CPITN and saliva tests in case of high caries risk. The dental care based on a basic and a risk strategy. The basic strategy included a complex symptomatic dental treatment and a dental prophylaxis, repeated once every 3 month. The patients were given instruction, demonstration, remotivation, professional oral hygiene measures and topical application of fluorides. The 4-year preventive intervention resulted in an improved consultation and oral hygiene behaviour. The nutritional behaviour did not change essentially. Within the cohort plaque index decreased from 1.01 to 0.68, the GPM/T index from 11.7 to 10.4 as well as the preventive care needs. It was found a low caries increment. The care concept with preventive emphasis is recommendable by its effectiveness.


Binding of 125I-physalaemin to rat parotid acinar cells.
1. The binding of [125I]physalaemin to rat parotid acinar cells was investigated. 2. The [125I]physalaemin exhibited a small degree of specific binding that was rapid, reversible and saturable. 3. The EC50 values for inhibition of binding by four peptides were well correlated with their ability to activate Ca-dependent K release from the rat parotid gland. 4. The number of binding sites, which may represent substance P receptors, was estimated to be in the range of 200/cell, a value quite different from those reported previously for muscarinin (840/cell) or alpha-adrenergic (15,000/cell) receptors. 5. It is concluded that if, as previously suggested, these receptors regulate the same population of Ca channels, then the mechanism or perhaps efficiency by which this is achieved may differ for the three receptors.


Optimizing prostate biopsy strategies for the diagnosis of prostate cancer.
The importance of prostate biopsy in urologic practice has been magnified by the routine use of serum prostate-specific antigen in prostate cancer screening. Given the potential impact of the procedure on both patient care and health care costs, an optimal strategy for accurate and judicious detection of early prostate cancer is imperative. Maintaining maximal sensitivity and negative predictive value are equally important to the patient. In this article, we review recent modifications in prostate biopsy indications and techniques that may allow for a systematic biopsy approach to the patient in whom prostate cancer is suspected.


Measurement of tetracycline levels in parakeets.
Parakeets were fed hulled millet seed containing 0.5% chlortetracycline (CTC) or minocycline. Blood concentrations of more than 1 micrograms CTC/ml and more than 5 micrograms minocycline/ml were obtained. Equivalent drug assay results were obtained from blood specimens collected by venipuncture or by use of treated filter-paper discs. The latter is a fairly simple method for assaying CTC concentrations in blood of treated psittacines.


Gender association of prayer for health - perspective from university students in Islamabad and Rawalpindi.
The role of religion and spirituality in coping with disease and promoting health has been reported from many parts of the World. However, no scientific studies on the use of prayers for health and wellbeing have been reported from Pakistan. A cross-sectional survey, using a self-administered questionnaire, was conducted among 1342 graduate and undergraduate students in the twin cities of Islamabad and Rawalpindi. A huge majority of students had prayed for their own as well as their family members' health in the preceding three months. There is a need to better understand the role in Pakistan of prayers related to health.


Dopamine receptor parameters detected by [3H]spiperone depend on tissue concentration: analysis and examples.
The binding of lipophilic radioligands to homogenized tissue was investigated with the help of a simple, two-component model: a specific component reflects binding to a single and uniform population of sites; a nonspecific component reflects partitioning into the membrane and the entrapment of some drug present in the aqueous phase prior to separation of the particulate fraction. The results indicate that the capacity and the affinity of the receptor may be underestimated when the data are analyzed in terms of total rather than free radioligand. Errors in capacity arise when for a significant fraction of the radioligand access to the receptor is blocked by an unlabelled drug and this appears as nonspecific binding. This is most likely to occur when the partition coefficient is such that the free radioligand is located predominantly in the particulate phase. Errors in affinity reflect the tendency of the membrane to reduce the free concentration of a lipophilic drug in the aqueous phase. A further complication arises when a significant fraction of the total radioligand binds to the receptor. [3H]Spiperone binds to dopamine D2 receptors with a dissociation constant of about 50 pM and partitions into the particulate phase of brain homogenates with a membrane/buffer partition coefficient of 410. As expected, both capacity and affinity can appear to depend on the concentration of tissue used in the assay. If the partition coefficient is known, corrected estimates of both parameters can be obtained knowing only the total concentration of radioligand; if the partition coefficient is not known, the free concentration of radioligand in the aqueous phase must be measured independently. The former procedure requires that the aqueous and particulate components of the system be separated by centrifugation; with filtration, the removal of an indeterminate amount of radioligand from the membrane during washing precludes any correction based on the partition coefficient. For the specific example of [3H]spiperone in human brain, the artifacts become negligible at concentrations of protein below 0.1 mg/ml of incubate. The capacity per unit of original tissue is best determined using unwashed preparations, since about 30% of the total protein and a comparable percentage of the receptors are lost on washing.


A potent antimalarial benzoxaborole targets a Plasmodium falciparum cleavage and polyadenylation specificity factor homologue.
Benzoxaboroles are effective against bacterial, fungal and protozoan pathogens. We report potent activity of the benzoxaborole AN3661 against Plasmodium falciparum laboratory-adapted strains (mean IC50 32 nM), Ugandan field isolates (mean ex vivo IC50 64 nM), and murine P. berghei and P. falciparum infections (day 4 ED90 0.34 and 0.57 mg kg-1, respectively). Multiple P. falciparum lines selected in vitro for resistance to AN3661 harboured point mutations in pfcpsf3, which encodes a homologue of mammalian cleavage and polyadenylation specificity factor subunit 3 (CPSF-73 or CPSF3). CRISPR-Cas9-mediated introduction of pfcpsf3 mutations into parental lines recapitulated AN3661 resistance. PfCPSF3 homology models placed these mutations in the active site, where AN3661 is predicted to bind. Transcripts for three trophozoite-expressed genes were lost in AN3661-treated trophozoites, which was not observed in parasites selected or engineered for AN3661 resistance. Our results identify the pre-mRNA processing factor PfCPSF3 as a promising antimalarial drug target.


The role of hydrogen sulfide in gastric mucosal damage.
Gastrointestinal disease is a major global threat to public health. In the past few decades, numerous studies have focuses on the application of small molecule gases in the disease treatment. Increasing evidence has shown that hydrogen sulfide (H2S) has anti-inflammatory and anti-oxidative effects, and can regulate gastric mucosal blood flow in the gastric mucosa. After gastric mucosa damage, the level of H2S in the stomach decreases. Administration of H2S can protect and repair the damaged gastric mucosa. Therefore, H2S is a new target for the repair and treatment of gastric mucosa damage. In this review, we introduce the roles of H2S in the treatment of gastric mucosa damage and provide the potential strategies for further clinical treatment.


Immunohistochemical localization of polysialic acid in tissue sections: differential binding to polynucleotides and DNA of a murine IgG and a human IgM monoclonal antibody.
For immunolocalization of alpha(2-8)-linked polysialic acid, which forms part of the neural cell adhesion molecule (N-CAM), two monoclonal antibodies, MAb735 and IgMNOV, were employed. Both antibodies have previously been shown to bind the extremely low immunogenic capsular polysaccharide of group B meningococci, which also consists of alpha(2-8) polysialic acid, but not to other, even closely related forms of polysialic acid. Despite the identical polysaccharide specificity of these two MAb, we observed marked differences of the staining pattern in tissue sections. We showed that these differences in immunostaining were due to the crossreactivity of IgMNOV with polynucleotides and DNA. MAb735, however, was shown to react exclusively with alpha(2-8) polysialic acid. Moreover, the specificity of MAb735 proved to be unique among eleven other MAb directed against various bacterial polysaccharides, as it was the only one unreactive with polynucleotides. Thus, MAb735, the only IgG type mouse monoclonal antibody to polysialic acid thus far reported, can be considered a specific probe for the unambiguous detection of alpha(2-8) polysialic acid in tissue sections, and should therefore help to further elucidate the role of polysialic acid in developmental processes.


Bandlike Transport and Charge-Carrier Dynamics in BiOI Films.
Following the emergence of lead halide perovskites (LHPs) as materials for efficient solar cells, research has progressed to explore stable, abundant, and nontoxic alternatives. However, the performance of such lead-free perovskite-inspired materials (PIMs) still lags significantly behind that of their LHP counterparts. For bismuth-based PIMs, one significant reason is a frequently observed ultrafast charge-carrier localization (or self-trapping), which imposes a fundamental limit on long-range mobility. Here we report the terahertz (THz) photoconductivity dynamics in thin films of BiOI and demonstrate a lack of such self-trapping, with good charge-carrier mobility, reaching ∼3 cm2 V-1 s-1 at 295 K and increasing gradually to ∼13 cm2 V-1 s-1 at 5 K, indicative of prevailing bandlike transport. Using a combination of transient photoluminescence and THz- and microwave-conductivity spectroscopy, we further investigate charge-carrier recombination processes, revealing charge-specific trapping of electrons at defects in BiOI over nanoseconds and low bimolecular band-to-band recombination. Subject to the development of passivation protocols, BiOI thus emerges as a superior light-harvesting semiconductor among the family of bismuth-based semiconductors.


Alcohol use and hypertension. Clinical considerations and implications.
Alcohol abuse is a more frequent contributor to hypertension than is generally appreciated. Although hypertension is transitory in most alcoholics and may not be evident after a short period of abstinence, it is potentially dangerous. Paroxysms of hypertension might result in target-organ damage. Hypertension may be the causal link to the increased incidence of stroke and coronary heart disease observed in problem drinkers as well as a contributor to the pathogenesis of alcoholic cardiomyopathy. Because of its transitory nature, however, alcohol-associated hypertension may, regrettably , be dismissed as inconsequential. Thus, a major potential cause of cardiovascular morbidity may go untreated.


Posttraumatic renal artery stenosis. Cure of hypertension by late revascularization.
Renal artery stenosis causing hypertension may be the sequel of blunt nonpenetrating abdominal trauma. Early recognition of such renal artery injury is essential. In the case reported, late recognition of unilateral traumatic renal artery stenosis led to surgical correction of the lesion and lasting cure of hypertension.


p38 MAPK inhibitors ameliorate target organ damage in hypertension: Part 1. p38 MAPK-dependent endothelial dysfunction and hypertension.
Numerous mediators, believed to play a role in endothelial dysfunction (e.g., neurohormones, cytokines, hypoxia, and stretch), have been shown to activate p38 mitogen-activated protein kinase (MAPK) in a variety of cell types. The purpose of the present study was to examine the regulation of p38 MAPK in endothelium and its role in endothelial dysfunction and salt sensitivity. In cultured human umbilical vein endothelial cells (HUVECs), tumor necrosis factor-alpha and lipopolysaccharide increased phosphorylation of p38 MAPK (P-p38 MAPK) and increased ICAM-1 expression. Preincubation with highly selective p38 MAPK inhibitors, 1-(1,3-dihydroxyprop-2-yl)-4-(4-fluorophenyl)-5-[2-phenoxypyrimidin-4-yl] imidazole (SB-239063AN) or SB-239063, dose dependently reduced intercellular adhesion molecule-1 expression in HUVECs. In spontaneously hypertensive-stroke prone rats (SHR-SP), P-p38 MAPK was localized by immunohistochemistry to the aortic endothelium and adventitia but was undetectable in aortae from normotensive rats. Introduction of a salt/fat diet (SFD) to the SHR-SP strain induced endothelial dysfunction (ex vivo vascular reactivity analysis), albuminuria, and an increase in blood pressure within 4 weeks. Chronic dietary dosing (approx. 100 mg/kg/day) with SB-239063AN inhibited the SFD diet-induced hypertension. In addition, delayed treatment also significantly improved survival and restored nitric oxide-mediated endothelium-dependent relaxation in SFD-SHR-SPs with established endothelial dysfunction. These results suggest an important role for p38 MAPK in endothelial inflammation and dysfunction as well as providing the first evidence for p38 MAPK-dependent hypertension.


Accuracy of a faecal immunochemical test in patients under colonoscopy surveillance of colorectal adenoma and cancer.
Surveillance of colorectal neoplasia place great strain on colonoscopy resources, and faecal immunochemical tests (FIT) are under-investigated for this purpose. The aim of this study was to report the outcome of FIT among patients scheduled for post-polypectomy and post-resection colorectal cancer (CRC) surveillance. Patients scheduled for colonoscopy surveillance at five endoscopy units in mid-Sweden in 2016-2020 were eligible. They provided a faecal sample from 2 separate days, which were analysed by iFOBT QuikRead go® (Aidian Oy). Both the colonoscopies, and the FIT analyses were conducted by staff blinded to the other. Out of 216 included patients, 157 (73%) underwent both a complete colonoscopy and had at least one FIT analysed prior to the examination. The indication for surveillance was previous adenoma in 69 (44%) and post-resection CRC in 88 (56%) patients. Two (1%) in the CRC surveillance group were diagnosed with a metachronous CRC, whereas 49 (56%) patients in the CRC surveillance, and 17 (25%) in the adenoma group had no pathology identified at colonscopy (P < 0.001). The proportion of patients diagnosed with adenomas requiring surveillance according to European Society of Gastrointestinal Society (ESGE) guidelines 2020 was 6 (7%) in the post-CRC resection versus 7 (10%) in the adenoma surveillance group (P = 0.4). Based on one FIT and at cut-off 10 µg Hb/g, sensitivity for CRC was 100%, specificity 83% (95% confidence interval [CI]: 77-89), Positive Predictive Value (PPV) 7% (-2 to 16) and Negative Predictive Value (NPV) 100%. All patients with an adenoma requiring surveillance had a FIT below this cut-off. Adding a second FIT decreased the specificity. Larger studies to evaluate the accuracy and consequences of using FIT for surveillance of colorectal neoplasia are needed. FIT may be more interesting for post-resection CRC surveillance than follow-up of adenoma.


Clinical Features, Pathogenesis, and Treatment of Large Granular Lymphocyte Leukemias.
Large granular lymphocytes (LGLs) are large lymphocytes with azurophilic granules in their cytoplasm. LGLs are either natural killer (NK) cells or T lymphocytes. Expansions of the LGLs in the peripheral blood are seen in various conditions, including three clonal disorders: T-cell LGL (T-LGL) leukemia, chronic lymphoproliferative disorders of NK cells (CLPD-NK), and aggressive NK-cell leukemia (ANKL). However, the monoclonal and polyclonal expansion of LGLs has been associated with many other conditions. The present article describes these LGL disorders, with special emphasis on the clinical features, pathogenesis, and treatments of the three above-mentioned clonal disorders.


Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach.
To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects reproducibility and the required sample size. For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects. Regions of interest were automatically delineated on co-registered MR and PET images. In cortical brain regions with a high density of 5-HT2A receptors, the outcome parameter (binding potential, BP1) showed high reproducibility, with a median difference between the two group measurements of 6% (range 5-12%), whereas in regions with a low receptor density, BP1 reproducibility was lower, with a median difference of 17% (range 11-39%). Partial volume correction reduced the variability in the sample considerably. The sample size required to detect a 20% difference in brain regions with high receptor density is approximately 27, whereas for low receptor binding regions the required sample size is substantially higher. This study demonstrates that [18F]altanserin PET with a bolus/infusion design has very low variability, particularly in larger brain regions with high 5-HT2A receptor density. Moreover, partial volume correction considerably reduces the sample size required to detect regional changes between groups.


[30th Annual Meeting of the European Society for Vascular Surgery (Copenhagen, Denmark, september 28-30, 2016)].
The article is a brief review of the proceedings of the 30th Annual Meeting of the European Society for Vascular Surgeons, held on September 28-30, 2016 in Copenhagen, Denmark. The papers presented reported the results of managing patients with pathology of carotid arteries, aortic aneurysms, pathology of peripheral arteries, also discussing current achievements and prospects of methods of treatment of arterial and venous diseases.


Treatment of NRAS-mutated advanced or metastatic melanoma: rationale, current trials and evidence to date.
The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15-25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment. We will review current preclinical and clinical developments in NRAS-mutated melanoma, and analyze ongoing clinical trials that are evaluating the benefit of different targeted and immune-based therapies, either tested as single agents or in combination, in NRAS-mutant melanoma.


Linked color imaging improves detection of minimal change esophagitis in non-erosive reflux esophagitis patients.
Background and study aims Non-erosive reflux disease (NERD) includes minimal change esophagitis (MCE) and no endoscopic abnormalities. However, for most endoscopists, it is difficult to detect MCE with conventional white-light endoscopy (WLE). Linked color imaging (LCI) technology is the most recently developed image-enhancing technology and improves detection and differentiation of subtle mucosal changes using a color contrast method. This study assessed the efficacy of WLE combined with LCI for diagnosing MCE compared with WLE. Patients and methods Between February and May 2017, 44 NERD patients and 40 healthy subjects were enrolled in our study. First, the distal esophagus was examined using WLE followed by LCI. Second, three experienced endoscopists observed all the patients' white-light (WL) images and corresponding images of WL and LCI and then recorded presence or absence of minimal change esophagitis (MCE +/-). The proportion of minimal change between the two groups was then compared. Third, five blinded endoscopists with different levels of endoscopic experience assessed whether MCE was present. Intraobserver reproducibility and interobserver agreement were described using the kappa value. Results The proportion of MCE in the NERD group (70.8 %, 35/48) was higher than that in the control group (22.5 %, 9/40, P < 0.001) when diagnosed by the three experienced endoscopists. Detection rates for MCE using WLE combined with LCI were higher than those using WLE (43/88, 48.9 % vs. 29/88, 33.0 %, P < 0.001). With WLE combined with LCI, intraobserver reproducibility significantly improved, indicating that the combined approach can improve interobserver agreement compared with using WLE alone. Conclusions Endoscopic diagnosis of MCE using WLE combined with LCI images is effective. Intraobserver reproducibility and interobserver agreement in MCE can be improved when LCI is applied with conventional imaging (Clinical trial registration number: NCT03068572).


Corneal thickness mapping by 3D swept-source anterior segment optical coherence tomography.
To assess accuracy and repeatability of central corneal thickness (CCT) measurements obtained by swept-source anterior segment optical coherence tomography (AS-OCT), spectral-domain retinal OCT with corneal module and ultrasound pachymetry (USP), and to assess repeatability of pachymetric mapping with AS-OCT. 50 healthy volunteers were recruited. A single, experienced operator analysed the right eye of each participant twice in the same session with AS-OCT ('corneal map' routine), retinal OCT and USP. CCT measurements were compared using repeated-measures analysis of variance, Bonferroni test, Pearson correlation and Bland-Altman plots. Repeatability of thickness maps and CCT measurements were assessed using Alpha of Cronbach, intraclass correlation coefficient (ICC) and coefficient of repeatability. Mean CCT±SD was 540±28.9 μm for AS-OCT, 544±29.5 μm for retinal OCT and 549.3±31.7 μm for USP; the differences were statistically significant (p<0.01). CCT measurements obtained with the three instruments were highly correlated: r was 0.965 for AS-OCT/USP, 0.962 for retinal OCT/USP and 0.984 for AS-OCT/retinal OCT comparison. The repeatability of CCT measurements was higher for AS-OCT than for the other devices (p<0.001). Repeatability of pachymetric maps was excellent (ICC=0.999). Pachymetric maps by swept-source AS-OCT showed excellent repeatability. CCT measurements obtained by AS-OCT, USP and retinal OCT were highly correlated although not identical.


Human malignant thyroid tumors displayed reduced levels of transforming growth factor beta receptor type II messenger RNA and protein.
Transforming growth factor beta (TGF-beta) is a physiological regulator of thyroid epithelial cell growth and differentiation. This factor signals through a heteromeric complex composed of type I (TGF-beta receptor type I) and type II [TGF-beta receptor type II (TbetaRII)] receptors. Loss of TbetaRII expression has been related to resistance to TGF-beta inhibition of cell proliferation. In the present work, we analyzed the TbetaRII expression in a series of human thyroid tumors, from benign lesions (adenomas) to neoplastic lesions of increasing aggressiveness (papillary and follicular carcinomas) up to the extremely aggressive anaplastic tumors. Results obtained indicated a clear reduced expression of TbetaRII mRNA only in the group of thyroid carcinomas when compared with their relative normal tissues. Immunohistochemical analyses with specific anti-TbetaRII antibodies confirm these observations. These data indicate that loss of expression of TbetaRII can contribute to thyroid cancer progression, inducing cancer cells to escape the growth-inhibitory effect of TGF-beta.


[Effect of high dose glucose-insulin-potassium infusion in patients with acute ST-segment elevation myocardial infarction: analysis of 7510 patients in China as part of CREATE-ECLA study].
To investigate the effect of high-dose glucose-insulin-potassium (GIK) infusion on the outcomes of ST-elevation myocardial infarction (STEMI) in China. As part of the international multicentre CREATE-ECLA study, 7510 patients with STEMI, aged (62 +/- 12), presenting their symptoms within 12 hours of onset who were hospitalized in 274 centers throughout China from July 2001 through July 2004 were randomized to receive GIK intravenous infusion for 24 hours plus routine treatment (3739) or control group (n=3771) receiving routine treatment alone. The patients were flowed up in the out-patient department 30 days after the randomization to assess the rates of mortality, cardiac arrest, cardiogenic shock and re-infarction. The median time from symptom onset to randomization was 5.8 hours. The mortality of the control group was 10.4%, not significantly different from that of the GIK group (11.2%, hazard ratio = 1.05, 95% CI: 0.916-1.207, P = 0.476). There rates of cardiac arrest, cardiogenic shock, and re-infarction of the GIK group were 0.8%, 6.8%, and 2.0% respectively, all not significantly different from those of the control group (1.0%, 6.4%, and 1.9% respectively, all P > 0.05). At the Day 7 the heart failure rate of the GIK group was 19.7%, not significantly different from that of the control group (18.3%, P = 0.102). The symptomatic hypotension rate of the GIK group was 3.7%, significantly higher than that of the control group (1.2%, P < 0.01). The phlebitis rate of the GIK group was 2.2%, significantly higher than that f the control group (0.1%, P < 0.01). The net increased fluid volume of the control group wasl3 584 ml. more than that of the GIK group (1036 ml). High dose GIK infusion has neutral effect on mortality, cardiac arrest or cardiogenic shock in patients with acute STEMI in China.


Crystallization of a chitosanase from Streptomyces N174.
Chitosanases are produced by many soil fungi and bacteria to degrade chitosan present in fungal cell walls. Here, we report the crystallization of a 29,500 dalton protein with chitosan endo-hydrolase activity isolated from Streptomyces N174. The crystals were grown by vapor diffusion. They are mechanically strong and diffract to at least 1.9 A resolution. The crystals belong to the monoclinic space group P2(1) with unit cell parameters a = 56.4 A, b = 59.6 A, c = 86.1 A and beta = 96.6 degrees. Cell parameters and crystal density are consistent with two chitosanase molecules per asymmetric unit.


Superficial herpes simplex virus wound infection following lung transplantation.
Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution.


Upconversion Nanoprobes Based on a Horseradish Peroxidase-Regulated Dual-Mode Strategy for the Ultrasensitive Detection of Staphylococcus aureus in Meat.
Staphylococcus aureus (S. aureus) is one of the foodborne pathogens that can cause infectious diseases and food poisoning. Herein, colorimetric and fluorescent dual-mode nanoprobes were developed for ultrasensitive detection of S. aureus to immediately respond to public health emergencies, reduce false positives, and improve measurement accuracy and persuasiveness. The nanoprobe consists of aptamer-labeled magnetic nanoparticles (apt-MNPs) as the capture signal probe and horseradish peroxidase and complementary DNA-functionalized upconversion nanoparticles (HRP-UCNPs-cDNA) as the chromogenic signal probe. In the absence of S. aureus, the probe forms an immune complex through base complementation with an observable signal. When S. aureus is introduced to this system, it preferentially binds to the apt-MNPs, releasing HRP-UCNPs-cDNA from the apt-MNPs and restoring the chromogenic probe signal. Under optimum conditions, an ultrasensitive assay of S. aureus was obtained, with limits of detection of 22 CFU mL-1 for fluorescence and 20 CFU mL-1 for colorimetry in a linear range of 56-5.6 × 106 CFU mL-1. Additionally, the standard plate counting method confirmed the reliability and accuracy of the established nanoprobe with an insignificant difference. Hence, the developed dual-mode platform has extensive application prospects for speedy and specific determination of S. aureus in meat.


Streptokinase resistance test in a group of Mediterranean people and its possible variations as regards sex and age.
A streptokinase resistance test (SK-RT) was studied on a group of people from the Mediterranean coast of Spain. It was found that 87.5% of the studied population required a dose of 250,000 U or less to obtain an adequate neutralization of the circulating antibodies. In none of the cases was the required dose higher than 500,000 U. The average dose was of 132,969 U (SD = 102,269). No significant differences were found between the dose required for men and that required for women. A significantly inferior dose to the average was, however, required for people over 50 years old (x = 112,280, SD = 100,459).


Notes on the genus Tunga (Siphonaptera: Tungidae) II--neosomes, morphology, classification, and other taxonomic notes.
This review focuses on the neosomes, morphology, and taxonomy of adult species of the genus Tunga, complementing the previously published data on the phylogeny, ecology, and pathogenic role. Neosomes are structures formed after penetration of adult females into the skin of hosts resulting in significant enlargement, being the most characteristic and most frequently observed form in hosts. Neosomes can be differentiated by shape, measurements, and sites of attachment to principal hosts. The taxonomic value and morphometric data of the most widely used characteristics to separate species - such as frontal curvature, head chaetotaxy, preoral internal sclerotization, ventral and dorsal genal lobes, eyes, maxillary palps, fusion of pronotum and mesonotum, metacoxae, metatarsi chaetotaxy, spermatheca (females), manubrium, basimere, telomere, and phallosome (males) - are comparatively analyzed. The sexes, individual variations, undescribed species, higher taxa, as well as a proposal for division of the genus into two subgenera (Tunga and Brevidigita) are presented (as previously given by Wang). A key for females, males, and gravid females (neosomes) also is included for identifying the 13 known species. Data on host specificity and geographical distribution may also support the identification of Tunga species because some sand fleas and their hosts may have co-evolved.


Glycosylation is required for maintenance of functional voltage-activated channels in growing neocortical neurons of the rat.
Voltage-activated currents were studied in whole-cell patch-clamped rat neocortical neurons growing in culture and treated with tunicamycin (TU), an inhibitor of protein N-glycosylation. The size of the Na+ current decreased progressively in the presence of TU (1-2 microM). This decrease was faster in growing 5-14 day-old neurons (to ca. 40% of control after 24 hours of treatment) than in fully grown 20-40-day-old neurons (to ca. 40% of control after 68 hours of treatment). The fast transient K+ current (A-current) was abolished, and the delayed rectifier K+ current was markedly reduced by a 24 hour treatment with TU (1-2 microM) in growing neurons. In contrast, in fully grown neurons these currents were unaffected by the same TU treatment. The size of the Ca2+ current was significantly reduced following a 24 hour treatment with TU (1-2 microM) in neurons at early stages of differentiation, but remained stable in 20-40-day-old neurons. It is concluded that protein glycosylation, presumably of the channel proteins themselves, is important for the functional expression of voltage-activated channels in embryonic cortical neurons during the early stages of cell growth in culture; the channels become less dependent on glycosylation in mature neurons.


5-lipoxygenase: cellular biology and molecular pharmacology.
5-lipoxygenase (5-LO) plays an essential role in the biosynthesis of leukotrienes, proinflammatory mediators which are mainly released from myeloid cells. Whereas LTB(4) is a potent chemotactic and chemokinetic agent for a variety of leukocytes, the cysteinyl-leukotrienes C, D(4) and E(4) cause vascular permeability and smooth muscle contraction. In view of these properties, leukotriene synthesis inhibitors have been hypothesized to possess therapeutic potential for the treatment of asthma, allergic disorders and other inflammatory diseases. Whereas cysteinyl-leukotriene receptor antagonists possess potential for antileukotriene therapy in asthma, results from clinical trials with leukotriene synthesis inhibitors were less encouraging. The expression of 5-LO in mammals is tightly regulated. Enzymatic activity in vitro can be modulated by calcium, ATP, phosphatidylcholine and lipid hydroperoxides; nevertheless activation of cellular 5-LO in response to external stimuli is rather incompletely understood. Intensive research revealed that on cell stimulation, 5-LO redistributes to the nuclear membrane where it colocalizes with 5-lipoxygenase-activating protein and cytosolic phospholipase A(2). In addition, various cellular proteins interacting with 5-LO have been identified. It was suggested that enzyme phosphorylation could influence redistribution and cellular activity of 5-LO and that the cellular redox tone regulates 5-LO product formation. This review highlights the determinants of cellular 5-LO activity and summarizes the molecular pharmacology of 5-LO.


Grit personality of physicians and achievement of treatment goals in patients with system lupus erythematosus.
Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS. Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.


Association of APOE with tau-tangle pathology with and without β-amyloid.
This study tested the hypothesis that the association of apolipoprotein E (APOE) with paired helical filament tau (PHF-tau) tangle pathology differs in brains with and without β-amyloid. Participants were 1056 autopsied individuals from 2 clinical-pathologic cohort studies of aging and Alzheimer's disease (AD), the Religious Orders Study, and the Rush Memory and Aging Project. Neuropathologic measures were obtained using immunohistochemistry targeting β-amyloid and PHF-tau tangles in 8 brain regions. Linear regression was used to compare the relation of APOE ε4 and ε2 to PHF-tau-tangle density in persons with β-amyloid relative to persons without β-amyloid. We found an interaction between APOE ε4 carriers and presence of β-amyloid (β = -0.968, p = 0.013) such that the association of APOE ε4 with PHF-tau tangles was much stronger in brains with β-amyloid. Stratified analysis shows that the association of APOE ε4 with PHF-tau tangles was considerably stronger among those with β-amyloid (β = 0.757, p = 1.1 × 10(-15)) compared to those without β-amyloid which was not significant (β = -0.201, p = 0.424). Separately, APOE ε2 was associated with fewer tangles in brains with β-amyloid (β = -0.425, p = 7.6 × 10(-4)) compared to those without β-amyloid which was not significant (β = -0.102, p = 0.506). Thus, the presence of APOE ε4 and ε2 alleles was not associated with PHF-tau tangles in the absence of β-amyloid. The data provide additional evidence that PHF-tau tangles in the absence of β-amyloid may reflect a pathologic process distinct from Alzheimer's disease.


Kaempferol and Biomodified Kaempferol from Sophora japonica Extract as Potential Sources of Anti-Cancer Polyphenolics against High Grade Glioma Cell Lines.
The enzymatic hydrolysis of the extract of Sophora japonica by two glycosyl hydrolases (hesperidinase and galactosidase) was performed in order to obtain kaempferol (KPF)-enriched extract with an enhanced anticancer activity. The current study examined the effectiveness of both Sophora japonica extracts (before (KPF-BBR) and after (KPF-ABR) bioconversion reactions) in reducing cell viability and inducing apoptosis in human high-degree gliomas in vitro. Cytotoxicity was determined using an MTT assay. The effects of both compounds on the proliferation of glioma cell lines were measured using trypan blue exclusion, flow cytometry for cell cycle, wound healing (WH), and neurosphere formation assays. Cellular apoptosis was detected by DNA fragmentation and phosphatidylserine exposure. qPCR and luciferase assays evaluated NF-kB pathway inhibition. The survival rate of NG-97 and U-251 cells significantly decreased in a time- and dose-dependent manner after the addition of KPF-BBR or KPF-ABR. Thus, a 50% reduction was observed in NG-97 cells at 800 µM (KPF-BBR) and 600 µM (KPF-ABR) after 72 h. Both compounds presented an IC50 of 1800 µM for U251 after 72 h. The above IC50 values were used in all of the following analyses. Neither of the KPF presented significant inhibitory effects on the non-tumoral cells (HDFa). However, after 24 h, both extracts (KPF-BBR and KPF-ABR) significantly inhibited the migration and proliferation of NG-97 and U-251 cells. In addition, MMP-9 was downregulated in glioma cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) plus KPF-BBR and TPA+KPF-ABR compared with the TPA-treated cells. Both KPF-BBR and KPF-ABR significantly inhibited the proliferation of glioma stem cells (neurospheres) after 24 h. DNA fragmentation assays demonstrated that the apoptotic ratio of KPF-ABR-treated cell lines was significantly higher than in the control groups, especially NG-97, which is not TMZ resistant. In fact, the flow cytometric analysis indicated that KPF-BBR and KPF-ABR induced significant apoptosis in both glioma cells. In addition, both KPF induced S and G2/M cell cycle arrest in the U251 cells. The qPCR and luciferase assays showed that both KPFs downregulated TRAF6, IRAK2, IL-1β, and TNF-α, indicating an inhibitory effect on the NF-kB pathway. Our findings suggest that both KPF-BBR and KPF-ABR can confer anti-tumoral effects on human cell glioma cells by inhibiting proliferation and inducing apoptosis, which is related to the NF-κB-mediated pathway. The KPF-enriched extract (KPF-ABR) showed an increased inhibitory effect on the cell migration and invasion, characterizing it as the best antitumor candidate.


Contribution of rivaroxaban to the international normalized ratio when switching to warfarin for anticoagulation as determined by simulation studies.
This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co-administration period when switching from rivaroxaban to warfarin. We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothrombin time and INR values were simulated by use of phospholipid concentrations that matched Neoplastin Plus® and Innovin® reagents. To simulate the combined effects of rivaroxaban and warfarin on INR during switching, warfarin initiation was simulated by adjusting the magnitude of the warfarin effect to reach the desired target INRs over the course of 21 days. The warfarin effect values (obtained every 6 h) and the desired rivaroxaban plasma concentrations were used. Nomograms were generated from rivaroxaban induced increases in INR. The simulation had good prediction quality. Rivaroxaban induced increases in the total INR from the warfarin attributed INR were seen, which increased with rivaroxaban plasma concentration. When the warfarin only INR was 2.0-3.0, the INR contribution of rivaroxaban with Neoplastin Plus® was 0.5-1.2, decreasing to 0.3-0.6 with Innovin® at median trough rivaroxaban plasma concentrations (38 μg l(-1) ). The data indicate that measuring warfarin induced changes in INR are best performed at trough rivaroxaban concentrations (24 h after rivaroxaban dosing) during the co-administration period when switching from rivaroxaban to warfarin. Furthermore, Innovin® is preferable to Neoplastin Plus® because of its substantially lower sensitivity to rivaroxaban, thereby reducing the influence of rivaroxaban on the measured INR.


[Best time to administer coagulation factor XIII( Fibrogammin P) for postoperative intractable pancreatic fistula following gastrectomy for gastric cancer].
Coagulation factor XIII( Fibrogammin P, F XIII) has been used to treat postoperative pancreatic fistulas following gastrectomy for gastric cancer in Japan. However, little is known about the best timing to start this treatment for early recovery. This study was designed to examine the appropriate time to start Fibrogammin P treatment for pancreatic fistulas, based on nutritional and inflammatory parameters. We retrospectively examined 27 consecutive patients with Grade B or C pancreatic fistulas as defined by the International Study Group of Pancreatic Fistula( ISGPF) classification who underwent gastrectomy at our institute between 1997 and 2011. We analyzed data on total protein( TP), albumin (Alb), C-reactive protein( CRP), and hemoglobin( Hb) concentrations and white blood cell( WBC) and lymphocyte counts. We used this information to determine laboratory cut-off values that indicate the most advantageous time to start the administration of Fibrogammin P in order to achieve early recovery within 2 weeks. When Fibrogammin P administration was based on more than 2 cut-off values such as Alb>2.6 g/dL and Hb>9.0 g/dL and WBC<9,000/μL (p= 0.1563), early cure of pancreatic fistulas was achieved. The use of nutritional and inflammatory parameter values to determine the best time to administer Fibrogammin P may shorten the treatment period.


Prolonged hyperphagia with high-fat feeding contributes to exacerbated weight gain in rats with adult-onset obesity.
Leptin-resistant rats, when given a high-fat (HF) diet, have a delayed normalization of caloric intake and greater weight gain than those on a chow diet. Because aged, obese rats are leptin resistant, these data predict that they will also have a delayed normalization of caloric intake and exacerbated weight gain when provided a HF diet. To investigate this hypothesis, along with the consequences of a HF diet on voluntary wheel running, we compared various ages of rats on a HF or chow diet. HF-fed young rats spontaneously divided into diet-induced obese and diet-resistant rats. However, all aged rats were susceptible to the weight-gaining effects of HF feeding. Rate of initial weight gain was proportional to age, and peak caloric intake on the HF diet and the days required to normalize caloric intake to basal levels increased with age. Responsiveness to peripheral leptin before HF feeding revealed a dose-response decrease in food intake and body weight in the young but no responses in the aged to even the highest dose, 0.5 mg/day. In addition, both age and HF feeding decreased the tendency for wheel running, suggesting the propensity for inactivity with age and HF feeding may contribute to age-related obesity and accelerate the rate of diet-induced obesity. These results demonstrate that aged rats are more susceptible to the detrimental effects of a HF diet.


The mechanism of staphylococci resistance to methicillin: a critical analysis of dominant opinions.
Resistance to methicillin has been reported to be constantly associated with production of a novel penicillin-binding protein (PBP), indicated as PBP2a. This PBP is always present in strains that are homogeneously resistant to the drug, but is also constantly present in the strains heterogeneously resistant, where by far the vast majority of the cells are indeed sensitive to the antibiotic. This apparent lack of correlation between the presence of PBP2a and methicillin resistance has led to the idea, shared by most scientists, that the presence of PBP2a alone cannot explain resistance of staphylococci to methicillin. This confusion has implications also for clinical microbiology. In fact in in-vitro assays, not rarely, strains that are resistant to methicillin appear sensitive to other beta-lactams. However, clinical experience has demonstrated that when infections caused by methicillin-resistant staphylococci, which, in in vitro assays, become sensitive to other beta-lactams, are treated with the latter antibiotics, the incidence of failures is higher than that observed when the same antibiotics are used to treat infections caused by staphylococci sensitive to methicillin. Also in consideration of the fact that the mechanism of resistance to methicillin is not yet understood, many authors recommend to consider methicillin-resistant staphylococci as being in-vivo resistant also to the beta-lactams to which they may become sensitive in in-vitro assays. In the opinion of the authors, the mechanism of staphylococcal resistance to methicillin is reasonably explainable at least in its fundamental aspects. The present dominant opinions concerning methicillin-resistant staphylococci will be critically analyzed on the basis both of data presented in the literature and of data obtained in the authors' laboratory.


Stem cell delivery to kidney via minimally invasive ultrasound-guided renal artery injection in mice.
Cell-based therapies are promising treatments for various kidney diseases. However, the major hurdle in initiating therapeutic responses is the inefficiency of injection routes to deliver cells to the kidney parenchyma. Systemic injection, such as intravenous injection only delivers a small proportion of cells to the kidney. Whereas direct delivery, such as renal artery injection requires surgical procedures. A minimally invasive renal artery injection was therefore developed to enhance cell delivery to kidney. In this study, luciferase expressing human adipocyte derived stem cells (ADSC) were labelled with gold nanorods (GNR) and injected into the renal artery using ultrasound guidance. The ADSCs were tracked using bioluminescence and photoacoustic imaging serially over 7 days. Imaging confirmed that the majority of signal was within the kidney, indicative of successful injection and that the cells remained viable for 3 days. Histology showed co-localization of GNRs with ADSC staining throughout the kidney with no indication of injury caused by injection. These findings demonstrate that ultrasound-guided renal artery injection is feasible in mice and can successfully deliver a large proportion of cells which are retained within the kidney for 3 days. Therefore, the techniques developed here will be useful for optimising cell therapy in kidney diseases.


In vivo study of the effect of combining endostatin gene therapy with 32P-colloid on hepatocarcinoma and its functioning mechanism.
To investigate the therapeutic effect of combining 32P colloid radiotherapy with endostatin anti-angiogenesis therapy on hepatocellular carcinoma (HCC) cells. HCC mouse models were prepared using H22 cells and randomly divided into four groups. The mice were administered phosphate buffered saline (PBS), (32)Pcolloid, secretory endostatin encoding plasmid and combination of 32P and endostatin, respectively. Seven, 14 and 21 days after treatment the mice were sacrificed. Expression of endostatin was confirmed using western blot. Tumor growth rate, microvessel density (MVD) in the solid tumor and apoptotic index (AI) of tumor cells was analyzed using immunohistochemistry and TUNEL methods. (1): From the western blot results, 1400 bp endostatin specific protein bands were observed in the samples from groups 3 and 4, but not in the other two groups; (2): The tumor growth rate of groups 2, 3 and 4 was significantly decreased compared to group 1 and that of group 4 was significantly lower than group 2 and 3 (3): The MVD of group 1 was greatly higher than in the other groups (4): The AI of group 4 was dramatically higher than in the other groups. (32)Pcolloid radiotherapy or endostatin anti-angiogenesis therapy were able to inhibit the growth of HCC cells in vivo, while the combination of (32)P and endostatin showed much better therapeutic effect in HCC treatment.


Effects of Tenapanor on Cytochrome P450-Mediated Drug-Drug Interactions.
Tenapanor (RDX5791, AZD1722) is an inhibitor of sodium/hydrogen exchanger isoform 3 in development for the treatment of constipation-predominant irritable bowel syndrome and the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. We aimed to investigate whether tenapanor inhibits or induces cytochrome P450s (CYPs). In vitro experiments assessing the potential of tenapanor to affect various CYPs indicated that it could inhibit CYP3A4/5 (IC50 0.4-0.7 μM). An open-label, phase 1 clinical study (NCT02140268) evaluated the pharmacokinetics of the CYP3A4 substrate midazolam when administered with and without tenapanor. Healthy volunteers received a single oral dose of midazolam 7.5 mg on day 1 followed by tenapanor 15 mg twice daily on days 2 to 15, with an additional single 7.5-mg midazolam dose coadministered on day 15. Midazolam exposure was similar whether it was administered alone or with tenapanor (geometric least-squares mean ratio [90%CI] for [midazolam + tenapanor]/midazolam: area under the concentration-time curve, 107% [101% to 113%]; Cmax 104% [89.6% to 122%]). Findings were similar for metabolites of midazolam. These results indicate that tenapanor 15 mg twice daily does not have a clinically relevant impact on CYP3A4 in humans and suggest that tenapanor can be coadministered with CYP3A4-metabolized drugs without affecting their exposure.


Outcomes research: an essential component of the advanced practice nurse role.
More research is needed that focuses on the effectiveness of nursing interventions in clinical settings. Advanced practice nurses are in the best position to conduct these studies, given their clinical expertise, access to subjects, master's-level research education, and need to demonstrate the effectiveness of their own care practices. This article describes how to develop outcomes studies and to use and disseminate the findings. Advanced practice nurses are encouraged to develop and replicate outcomes studies and to broadly disseminate findings to build the evidence base needed to support advanced practice in nursing.


Medical factors associated with caregiver intention to vaccinate their children against COVID-19.
To describe medical factors that are associated with caregiver intention to vaccinate their children against COVID-19. We conducted a cross-sectional study of families receiving primary care in a mid-Atlantic pediatric healthcare system, linking caregiver-reported data from a survey completed March 19 to April 16, 2021 to comprehensive data from the child's EHR. 513 families were included (28% Black, 16% Hispanic, 44% public insurance, 21% rural, child age range 0-21 years). 44% of caregivers intended to vaccinate their children against COVID-19, while 41% were not sure and 15% would not. After adjusting for socio-demographics, the only medical factors that were associated with caregiver COVID-19 vaccine hesitancy were caregiver COVID-19 vaccination status at the time of the survey (aOR 3.0 if the caregiver did not receive the vaccine compared to those who did, 95% CI 1.7-5.3) and child seasonal influenza immunization history (aOR 3.3 if the child had not received the influenza vaccine in the 2020-2021 season compared to those who did, 95% CI 2.0-5.4). Other medical factors, including family medical experiences with COVID-19, other child immunization history, child health conditions like obesity and asthma, and family engagement with the healthcare system were not associated with caregiver intention to vaccinate their children against COVID-19. This study highlights important factors, such as general attitudes towards vaccines and understanding of COVID-19 morbidity risk factors, that healthcare providers should address when having conversations with families about the COVID-19 vaccine.


Molecular evolution of the internal transcribed spacers (ITS1 and ITS2) and phylogenetic relationships among species of the family Cucurbitaceae.
Phylogenetic relationships of different members of the family Cucurbitaceae were estimated from sequences of the internal transcribed spacer (ITS1 and ITS2) regions of the nuclear ribosomal RNA genes. Twenty-six species of different genera belonging to different tribes and several subtribes were analyzed. The whole ITS regions were amplified by PCR technique and cloned, and three to five different clones of each species were sequenced; for some species PCR products were sequenced directly. ITS1 and ITS2 regions are slightly variable in length, with each length appearing genus-specific. A substitution rate of 3.62 x 10(-9) substitutions per site per year was calculated assuming 40 MYA separation time. Phylogenetic relationships inferred from ITS sequences of some species is in agreement with morphological data, but deviations to the taxonomic classification were also observed. A polyphyletic origin of the New World species must be considered. In the genus Cucurbita different "types" of ITS sequences within one species exist, possibly due to the high frequency of introgression during domestication or due to polyploidization events; in contrast, low intraspecific variability was detectable in the genus Cucumis, indicating different stages of speciation.


A 1.02 μW Battery-Less, Continuous Sensing and Post-Processing SiP for Wearable Applications.
Improving system lifetime and robustness is a key to advancing self-powered platforms for real world applications. A complete self-powered, battery-less, wearable platform requires a microwatt-power system-on-chip (SoC), operating reliably within this budget, capable of surviving long periods without charging, and recovering from power loss to its previous state. To meet these requirements, we designed a wireless sensing heterogeneous system-in-package (SiP) containing an ultra-low power (ULP) SoC, a non-volatile boot memory (NVM), and a 2.4 GHz frequency shift key (FSK) radio, all integrated with custom ULP interfaces. The SoC includes a fully integrated energy harvesting platform power manager (EH-PPM) to power the SiP and other commercial sensors. The EH-PPM is designed for small loads and powers the SoC and peripherals while drawing very low operating current. The SoC also includes a digital system data-flow for sensing applications, an analog front end for ECG signal acquisition, and a cold-boot management system (CBMS) for boot and recovery from the NVM. The CBMS enables integration of the SoC with the ULP NVM to create a wearable formfactor, self-powered system capable of recovery from power loss. The SoC also includes a radio interface tightly integrated with a compression accelerator to efficiently communicate with the FSK transmitter and reduce the FSK's transmission time. This tight integration between accelerators on the SoC and peripherals is another feature that reduces the system's power consumption by reducing the code size and number of memory accesses required to perform an operation. The SoC consumes 507 nW average power while running free-fall detection, 519 nW average power while measuring ambient temperature, and 1.02 μW during continuous ECG monitoring and post-processing.


Bicytopenia and leukoerythroblastosis: a rare initial presentation of signet ring cell gastric adenocarcinoma.
Gastric adenocarcinoma is a common neoplasia and is responsible for up to 30% of the overall deaths due to cancer. Advanced disease is mostly characterized by peritoneum, liver, and lung involvement. The spread of the disease to the bone is rare, and bone marrow dissemination is even rarer. In this setting, leukoerythroblastosis may be the initial manifestation of the disease. The authors report the case of a 64-year-old Caucasian man who sought medical care complaining of back pain, weakness, and weight loss. The physical examination revealed pallor, and the laboratory work-up depicted severe anemia and thrombocytopenia; the peripheral blood smear was consistent with leukoerythroblastosis. The ongoing investigation through a bone marrow biopsy showed massive involvement of the bone marrow by a signet ring cell adenocarcinoma. During hospitalization, the patient presented melena, and an upper digestive endoscopy depicted an ulcerated and infiltrative lesion in the cardia, upon which the histological examination revealed a signet ring cell adenocarcinoma. This case highlights the bone marrow invasion represented by bicytopenia and leukoerythroblastosis as the initial manifestation of this histological type of gastric cancer. Although treatment attempts were made with chemotherapy and radiotherapy, the patient died early on, showing the aggressive behavior of this form of tumoral presentation.


Effects of perioperative enhanced recovery after surgery pathway management versus traditional management on the clinical outcomes of laparoscopic-assisted radical resection of distal gastric cancer: study protocol for a randomized controlled trial.
The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer. This study is a prospective, multicentre RCT. This experiment will consist of two groups - an experimental group and a control group - randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups. The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer. Chinese Clinical Trial Registry, CHiCTR1900022438. Registered on 11 April 2019.


Effects of the pulsed electron avalanche knife on retinal tissue.
To evaluate the precision of retinal tissue dissection by the pulsed electron avalanche knife (PEAK) and to assess possible toxic effects from this device. To demonstrate precision of cutting, bovine retina (in vitro) and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by scanning electron microscopy and histologic examination (light microscopy). To evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into the vitreous 1 cm above the retina. Histologic examinations and electroretinography were performed at intervals up to 1 month after exposure. Cuts in postmortem bovine retina showed extremely sharp edges with no signs of thermal damage. Full-thickness cuts in living attached rabbit retina were similarly sharp and were typically less than 100 microm wide. No signs of retinal toxic effects were detected by histologic examination or electroretinography. The PEAK is capable of precise cutting through retinal tissue, and there are no demonstrable retinal toxic effects from its use. The precision and tractionless nature of PEAK cutting offers advantages over mechanical tools and laser-based instrumentation. We believe this new device will prove useful in a variety of vitreoretinal surgical applications.


Treating pediatric atopic dermatitis: current perspectives.
Atopic dermatitis (AD) is a chronic, inflammatory skin condition which affects millions of people worldwide. It is most commonly seen in children but may also progress into adulthood. Management of this complex disease requires a multi-pronged approach which can address the myriad of issues which underscore its development. Avoidance of triggering factors is imperative in establishing consistent control of skin irritation while daily moisturization can be very effective in skin barrier repair and maintenance. Judicious use of anti-inflammatory medications has been shown to make a significant impact on both treatment as well as prevention of disease. Unfortunately, pruritus, a key feature of AD, has proven much harder to control. Finally, awareness of the risks of colonization and infection in patients with AD should be incorporated into their surveillance and management plans. While our understanding has progressed greatly regarding this disease, further research is still needed regarding future directions for both treatment and prevention.


Oxidative stress, gene expression, and protein changes induced in the human placenta during labor.
Malperfusion of the placenta has been implicated as a cause of oxidative stress in complications of human pregnancy, leading to release of proinflammatory cytokines and anti-angiogenic factors into the maternal circulation. Uterine contractions during labor are known to be associated with intermittent utero-placental perfusion. We therefore tested whether oxidative stress, proinflammatory cytokines, and angiogenic regulators were increased in placentas subjected to short (<5 hours) and long (>15 hours) labor compared with nonlabored controls delivered by cesarean section. In addition, broader changes in gene transcripts were assessed by microarray analysis. Oxidative stress, activation of the nuclear factor-kappaB pathway, tumor necrosis factor-alpha and interleukin 1beta all increased in placental tissues after labor. Stabilization of hypoxia-inducible factor-1alpha and increased vascular endothelial growth factor soluble receptor-1 were also observed. By contrast, tissue levels of placenta growth factor decreased. Apoptosis was also activated in labored placentas. The magnitude of these changes related to the duration of labor. After labor, 55 gene transcripts were up-regulated and 35 down-regulated, and many of these changes were reflected at the protein level. In conclusion, labor is a powerful inducer of placental oxidative stress, inflammatory cytokines, and angiogenic regulators. Our findings are consistent with intermittent perfusion being the initiating cause. Placentas subjected to labor do not reflect the normal in vivo state at the molecular level.


Roles of epsilon-near-zero (ENZ) and mu-near-zero (MNZ) materials in optical metatronic circuit networks.
The concept of metamaterial-inspired nanocircuits, dubbed metatronics, was introduced in [Science 317, 1698 (2007); Phys. Rev. Lett. 95, 095504 (2005)]. It was suggested how optical lumped elements (nanoelements) can be made using subwavelength plasmonic or non-plasmonic particles. As a result, the optical metatronic equivalents of a number of electronic circuits, such as frequency mixers and filters, were suggested. In this work we further expand the concept of electronic lumped element networks into optical metatronic circuits and suggest a conceptual model applicable to various metatronic passive networks. In particular, we differentiate between the series and parallel networks using epsilon-near-zero (ENZ) and mu-near-zero (MNZ) materials. We employ layered structures with subwavelength thicknesses for the nanoelements as the building blocks of collections of metatronic networks. Furthermore, we explore how by choosing the non-zero constitutive parameters of the materials with specific dispersions, either Drude or Lorentzian dispersion with suitable parameters, capacitive and inductive responses can be achieved in both series and parallel networks. Next, we proceed with the one-to-one analogy between electronic circuits and optical metatronic filter layered networks and justify our analogies by comparing the frequency response of the two paradigms. Finally, we examine the material dispersion of near-zero relative permittivity as well as other physically important material considerations such as losses.


Investigation on reference intervals and regional differences of platelet indices in healthy Chinese Han adults.
Reference intervals are important for interpretation of clinical laboratory tests. The platelet (PLT) indices such as the mean platelet volume (MPV) and platelet distribution width (PDW) are newer hematological parameters, which have been recently reported as clinically valuable biomarkers. However, there are not many studies that have estimated the reference intervals for these parameters in healthy Chinese Han adults. The objectives of this study were to establish reference values of PLT indices [including PLT count, MPV, PDW, platelet-large cell ratio (P-LCR), and plateletcrit (Pct)] for healthy Chinese Han adults. We also aimed to determine the region-based differences of PLT indices in China. A total of 4,642 volunteers with a mean age of 43 were recruited from six regions of China. PLT indices were performed on Sysmex XE-2100 hematology analyzers, whose traceability was well verified. There were significant region-based differences for all PLT indices. Reference people in Chengdu had the lowest mean PLT count and Pct, but the highest MPV, PDW, and P-LCR among the six regions. Therefore, we derived the reference intervals in Chinese Han population excluding Chengdu reference people for PLT indices as PLT count: (127-341) × 10(9)/l; MPV: (9.20-13.30) fl; PDW: 9.90-19.00%; P-LCR: 18.10-52.00%; Pct: 16.00-41.00%. Region-specific reference intervals are essential as there were statistically significant region-related differences in the PLT parameters. The reference intervals established in this study differed from the existing reference values. Chengdu region may need proper specific reference ranges, which apply to their people, for all PLT parameters.


Effects of age and frequency of stimulus repetitions on two-choice reaction time.
Binary choice-reaction times for 123 males, 25-79 years of age, were obtained in a sequence of discrete trials in which the proportion of occasions that the same stimulus was presented twice in succession varied from .25, .50, and .75 or from .75, .50, and .25 over successive thirds of the sequence. Stimulus alternations were responded to more rapidly than stimulus repetitions by subjects in all age groups, especially in trial blocks with .75 alterations. The absolute differences in mean reaction time to stimulus alterations and repetitions increased with age. The results are consistent with the hypothesis that reaction times are affected both by pre-existing expectations for stimulus alternations as well as expectations for stimulus alternations or repetitions developed during the course of the experiment. Mean response latency as well as between- and within-subject variability in performance increased with age. Analyses of frequency distributions of the reaction times indicated that the psychomotor component of reaction time increases with age while the decision-making component becomes more variable.


cAMP differentially regulates axonal and dendritic development of dentate granule cells.
Neurite polarity is a morphological characteristic of dentate gyrus granule cells, which extend axons to the hilar region and dendrites in the opposite direction, i.e. to the molecular layer. This remarkable polarity must require a differential system for axon and dendrite guidance. Here, we report that the axon and dendrites of a granule cell are differentially responsive to cAMP. In developing cultures of dispersed granule cells, dendritic growth cones were increased in number after pharmacological activation of cAMP signaling and decreased after blockade of cAMP signaling. Activation of cAMP signaling antagonized dendritic collapse induced by the potent repellents Sema3F and glutamate. In contrast to dendrites, axons were protected from Sema3F-induced collapse when cAMP signaling was inhibited. Axonal and dendritic growth cones both expressed type 1 adenylyl cyclase, but only axons showed a cAMP increase in response to Sema3F, and the elevated cAMP was sufficient to collapse axonal growth cones. Thus, the axons and dendrites of dentate granule cells differ in the regulation of cAMP levels as well as responsiveness to cAMP. cAMP may be crucial for shaping the information flow polarity in the dentate gyrus circuit.


Stabilizing effect of the transferred conjoined tendon on shoulder stability.
The modified Boytchev procedure, i.e., rerouting of the coracoid process with its attached conjoined tendon (short head of biceps and coracobrachialis) deep to the subscapularis and reattachment to its anatomical location, has been advocated for recurrent anterior glenohumeral instability with controversial clinical outcomes. We aimed to investigate the dynamic contribution of the conjoined tendon in situ or transferred to the glenohumeral articulation in stable and unstable shoulders. Eight cadaveric shoulders were tested with the arm in 90 degrees abduction and 90 degrees external rotation. A constant 1.5 kg anterior translation force was applied to the proximal humerus, combined with 0, 1.5, 3.0 kg of load applied to the conjoined tendon sequentially. Anterior displacement of the humeral head relative to the scapula was recorded before and after an imitation Bankart lesion was created, and after treated with the modified Boytchev procedure for the Bankart lesion. Application of load to the conjoined tendon significantly reduced anterior displacement of the humeral head either with the capsule intact or with Bankart lesion simulated. The most significant decrease of the anterior displacement occurred when the conjoined tendon was transferred beneath the subscapularis. Our findings show that the conjoined tendon per se has a stabilizing effect on stable and unstable shoulders and therefore provide scientific support for the treatment of recurrent shoulder instability using the modified Boytchev procedure.


Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers.
Imaging techniques targeting tumor angiogenesis have been investigated for past decade. Of these, the radiolabeled Arg-Gly- Asp (RGD) peptide has been focused because it has high affinity and selectivity for integrin alpha(v)beta3. Integrin alpha(v)beta3 is expressed on the plasma membrane in an active status in which it binds its ligands and transduce signals when exposed activating external stimuli of tumor angiogenesis such as vascular endothelial growth factor (VEGF). Many linear or cyclic RGD peptides were developed for positron emission tomography (PET). In this review, we focused on currently developed RGD peptides as PET probes for non-invasive detection of integrin alpha(v)beta3 expression.


Diffraction by a small aperture in conical geometry: application to metal-coated tips used in near-field scanning optical microscopy.
Light diffraction through a subwavelength aperture located at the apex of a metallic screen with conical geometry is investigated theoretically. A method based on a multipole field expansion is developed to solve Maxwell's equations analytically using boundary conditions adapted both for the conical geometry and for the finite conductivity of a real metal. The topological properties of the diffracted field are discussed in detail and compared to those of the field diffracted through a small aperture in a flat screen, i.e., the Bethe problem. The model is applied to coated, conically tapered optical fiber tips that are used in near-field scanning optical microscopy. It is demonstrated that such tips behave over a large portion of space like a simple combination of two effective dipoles located in the apex plane (an electric dipole and a magnetic dipole parallel to the incident fields at the apex) whose exact expressions are determined. However, the large "backward" emission in the P plane--a salient experimental fact that has remained unexplained so far--is recovered in our analysis, which goes beyond the two-dipole approximation.


Classification of tinnitus.
Classification in general serves a number of purposes. In relation to tinnitus there are particular problems because the cause in only rarely known and the mechanism is not known at all. This means that firm classifications tend to be misleading and serve little purpose other than to delude the doctor and the patient. The aim in this paper therefore is to examine the various ways in which information (whether scientific or clinical) about tinnitus can be organized so as to help diagnosis, management or research towards recognition of the fundamental abnormalities. Attempts at classification based on the site of the lesion and on speculation about its cause are described. Classification is analysed according to (1) patients' own reports, (2) doctors' clinical observations, (3) various techniques of measurement, (4) associated phenomena and (5) results of treatment. From these various aspects a pattern emerges which, though incomplete, at least exposes rather than obscures the gaps in our knowledge.


New developments in alpha-adrenoreceptor drugs for the treatment of hypertension.
The alpha 1- and alpha 2-adrenoreceptor types are defined in terms of the selective binding of radioligands and their displacement from membrane preparations by a range of agonists and antagonists. Their distribution is described in brain, kidney, heart, and peripheral blood vessels. A group of centrally acting clonidine-like drugs are classified in terms of their selectivity for the alpha 2-adrenoreceptors, and it is suggested that differences between alpha-adrenoreceptors in various tissues may allow development of highly selective alpha 2-adrenoreceptor agonists for specific tissue sites such as the juxtaglomerular cells and brainstem nuclei controlling blood pressure. It is further suggested that the aim of treatment with such compounds is to modulate adrenergic activity while retaining normal homeostatic mechanisms. For this purpose, competitive agonists and antagonists are preferable to compounds which bind irreversibly to the receptor.


[Two wheels - too dangerous? Analysis of real-world crash data and federal statistics].
Motorcyclists profit from improved safety measures and medical care only slightly compared with other road users. The aims of this study were to gain new insights into crash mechanisms and the resulting injuries of motorcyclists and to understand trends in road traffic accident statistics over the last 10 years. In our prospective analysis we documented data from collisions in which at least one subject sustained an injury of 2-6 on the Maximum Abbreviated Injury Scale (MAIS). Additionally, key parameters published by the German Federal Statistical Office were analysed. Data were studied for 66 motorcycle crashes and 66 injured subjects. The mean ISS was 17.9, with injuries of the lower limb (44%) and head (41%) being the most frequent in motorcyclists. Psychometric questionnaires revealed that motorcyclists had a significantly higher willingness to take risks compared with drivers of other vehicles. Federal statistics revealed a dramatic increase in mortality in the first months of 2007, but in the next months, mortality decreased to levels comparable to those of the preceding year. Knowledge of crash mechanisms, injury patterns and profiles of high-risk drivers can help reduce the collision rates and injury severity of motorcyclists.


MS patients with depressive symptoms exhibit affective memory biases when verbal encoding strategies are suppressed.
As many as 50% of multiple sclerosis (MS) patients experience clinical or subclinical depression. A voluminous literature has documented affective memory biases (AMB) among depressed individuals. Despite this, little is known regarding how depressive symptoms may affect MS patients' ability to recall positive and negative material. The present study employed an affective list-learning task that increased cognitive load and inhibited the use of higher order encoding strategies. The purpose of the study was twofold: to determine whether MS patients exhibit AMB and to examine whether subvocal repetition and other higher order encoding strategies are essential to the formation of AMB among people experiencing depression. Results indicated a strong relationship between depression and AMB in MS. The results are discussed in relation to existing biological research that indicates limbic and/or other subcortical systems may play a role in the formation of AMB.


Factors Influencing Birth Preparedness in Rapti Municipality of Chitwan, Nepal.
Birth preparedness is crucial for health quality of mother and newborn and acts as a strong contributor in mitigating maternal and newborn mortalities. Different factors are predicted to have an influence upon birth preparedness practice. This paper aims at exploring relationship between various factors and birth preparedness practice. A cross-sectional study design was used to find out the relationship between various factors and birth preparedness practice. One hundred sixty-five women residing at ward number 1 of Rapti Municipality, Chitwan who delivered in the last twelve months were selected consecutively and interviewed using a semistructured questionnaire. The collected data were analyzed using descriptive and bivariate techniques. Three quarters (75.2%) of the respondents had better birth preparedness, institutional delivery was 63.0%, antenatal care (ANC) visit as per protocol was about 62.0%, and about 90% of the respondents had received counseling during ANC. Age, religion, family types, education, age at marriage, parity, number of children, knowledge on birth preparedness, knowledge on danger sign, place for ANC and delivery, and decision-makers were found to be statistically significant (P value < 0.05) with birth preparedness practice. Better knowledge on birth preparedness led to a better preparedness status. Age, religion, family type, education of women and partners, parity, and number of children were the factors that influence birth preparedness. Counseling during ANC played a significant role in birth preparedness.


A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells.
PTEN is a tumor-suppressor gene that has been shown to be under the regulatory control of a PTEN pseudogene expressed noncoding RNA, PTENpg1. Here, we characterize a previously unidentified PTENpg1-encoded antisense RNA (asRNA), which regulates PTEN transcription and PTEN mRNA stability. We find two PTENpg1 asRNA isoforms, α and β. The α isoform functions in trans, localizes to the PTEN promoter and epigenetically modulates PTEN transcription by the recruitment of DNA methyltransferase 3a and Enhancer of Zeste. In contrast, the β isoform interacts with PTENpg1 through an RNA-RNA pairing interaction, which affects PTEN protein output through changes of PTENpg1 stability and microRNA sponge activity. Disruption of this asRNA-regulated network induces cell-cycle arrest and sensitizes cells to doxorubicin, which suggests a biological function for the respective PTENpg1 expressed asRNAs.