Decreased gastro-intestinal responses to certain agonists in streptozotocin- and alloxan-diabetic rats in vitro.
In this study, the beta-adrenergic, muscarinic and serotonergic receptor activities were investigated in alloxan- and streptozotocin-diabetic rats using duodenum, ileum and gastric fundus strips as assay organs. In addition, the effect of manganese chloride on the duodenum of normal and diabetic rats was studied to understand whether it affects the gastro-intestinal adenylate cyclase activity. The results obtained in this study suggest that no significant changes occur in the gastro-intestinal muscarinic receptor and adenylate cyclase activities due to experimental diabetes. Nevertheless, the experiments performed on the rat duodenum and gastric fundus strips with salbutamol and serotonin showed that the beta-adrenergic and serotonergic receptor activities of the gastro-intestinal tract decreased significantly in alloxan- and streptozotocin-induced diabetes. The results obtained seem to show that the gastro-intestinal complication(s) of the diabetes were related to the reduction(s) of the beta-adrenergic and/or serotonergic receptor activities.


Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge.
Case Presentation. A 69-year-old Hispanic male, with a past history of diabetes and coronary disease, was admitted for fever, diarrhea, and confusion of 4 weeks duration. Physical examination showed a disoriented patient with multiple ecchymoses, possible ascites, and bilateral scrotal swelling. Hemoglobin was 6.7, prothrombin time (PT) 21.4 seconds with international normalized ratio 2.1, partial thromboplastin time (PTT) 55.6 seconds, fibrin split 10 µg/L, and lactate dehydrogenase (LDH) 1231 IU/L. Except for a positive DNA test for Epstein-Barr virus (EBV) infection, extensive diagnostic workup for infections, malignancy, or a neurological cause was negative. Mixing studies revealed a nonspecific inhibitor of PT and PTT but Factor VIII levels were normal. The patient was empirically treated with antibiotics but developed hypotension and died on day 27 of admission. At autopsy, patient was found to have intravascular diffuse large B-cell lymphoma involving skin, testes, lung, and muscles. The malignant cells were positive for CD20, CD791, Mum-1, and Pax-5 and negative for CD3, CD5, CD10, CD30, and Bcl-6. The malignant cells were 100% positive for Ki-67. Discussion. Intravascular large cell B-cell lymphoma (IVLBCL) is rare form of diffuse large B-cell lymphoma and tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules. The cause of its affinity for vascular bed remains unknown. In many reports, IVLBCL was associated with HIV, HHV8, and EBV infections. The fact that our case showed evidence of EBV infection lends support to the association of this diagnosis to viral illness. The available literature on this subject is scant, and in many cases, the diagnosis was made only at autopsy. The typical presentation of this disorder is with B symptoms, progressive neurologic deficits, and skin findings. Bone marrow, spleen, and liver are involved in a minority of patients. Nearly all patients have elevated LDH, and about 65% are anemic. About 20% have hepatic and renal dysfunction. The treatment consists of systemic chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone plus rituximab (CHOP-R) and central nervous system prophylaxis. Retrospective data suggests that, with treatment, 51% to 82% of the patients achieve a complete remission and 27% to 56% are alive at 2-year follow-up. Conclusion. IVLBCL is a difficult diagnosis to make as the disease remains confined to the vascular lumen. It may be associated with certain viral illnesses, and this association needs to be explored further. It is important to consider this diagnosis in the appropriate settings because patients may achieve durable remissions with therapy.


Diagnosis of colon cancer differs in younger versus older patients despite similar complaints.
Colon cancer is common, affecting mostly older people. Since age is a risk factor, young patients might not be given the same attention as older ones regarding symptoms that could imply the presence of colon cancer. To investigate whether young patients, i.e., under age 50, complain of symptoms for longer than older patients until the diagnosis of colon cancer is established. In this retrospective cohort study, patients were divided into two groups: < 50 years old (group 1) and > or = 50 (group 2). All had undergone surgery for left or right-colon cancer during the 10 year period of the study from January 2000 through December 2009 at one medical center. Rectal and sigmoid cancers were excluded. Data collected included age, geander, quantity and quality of complaints, duration of complaints, in-hospital versus community diagnosis, pathological staging, the side of colon involved, and overall mortality. The primary outcome was the quality and duration of complaints. Secondary outcomes were the pathological stage at presentation and the mortality rate. The study group comprised 236 patients: 31 (13.1%) were < 50 years old and 205 (86.9%) were > or = 50. No significant difference was found in the quantity and quality of complaints between the two groups. Patients in group 1 (< 50 years) complained for a longer period, 5.3 vs.2.4 months (P= 0.002). More younger patients were diagnosed with stage IV disease (38.7% vs. 21.5%, P= 0.035) and fewer had stage I disease (3.2% vs. 15.6%, P= 0.06); the mortality rates were similar (41.9% vs. 39%). Applying a stepwise logistic regression model, the duration of complaints was found to be a predictor of mortality (P= 0.03, OR 1.6, 95% CI 1-3.6), independently of age (P= 0.003) and stage (P< 0.001). Younger patients are more often diagnosed with colon cancer later, at a more advanced stage. Alertness to patients' complaints, together with evaluation regardless of age but according to symptoms and clinical presentation are crucial. Large-scale population-based studies are needed to confirm this trend.


The effects of extrinsic context on nicotine discrimination.
There is evidence from memory studies that context acquired in parallel with the encoded material will facilitate retrieval. However, relatively little is known of how context affects drug discrimination behaviour in humans. The present study employs conventional drug discrimination procedures to investigate the effects of music, as an external cue, on nicotine drug discrimination. Subjects were trained to discriminate a low dose of nicotine (1 mg) from placebo while listening to two different types of music [elated (EL) and depressant (DE): thought to induce happy and sad mood respectively]. Half of the subjects received EL music with nicotine and DE with placebo and the other half vice versa. At the end of training, subjects who reached the criterion (80% of trials identified correctly) entered the generalization phase and were required to discriminate different doses of nicotine (0, 0.25, 0.5 and 1 mg) by indicating how similar each sample was to the training dose. Generalization took place in the presence of either EL or DE music. Nicotine-appropriate responding during generalization was linearly related to dose, with subjects being able to distinguish 0.5mg of nicotine from placebo. Nicotine-appropriate responding at generalization was higher when the context (type of music) was the same as the one employed during discrimination training when nicotine was administered (i.e. a context-dependent generalization effect was present). In addition, it was shown that the context-dependent effect was due to the properties of the EL music. These data provide the first evidence that extrinsic context can facilitate nicotine discrimination in humans. In addition, the findings suggest that this facilitatory effect is not a general effect but is sensitive to specific attributes of the context.


Cytokine production by subsets of CD4 memory T cells differing in P-glycoprotein expression: effects of aging.
We have shown previously that the mouse CD4 memory cell subset can be divided into two subpopulations based on differential expression of P-glycoprotein. Cells with high levels of P-glycoprotein can be detected by extrusion of the fluorochrome Rhodamine 123; they are referred to as R123lo cells. These R123lo T cells increase with age and have been shown not to respond to anti-CD3 and IL-2 by proliferation or IL-4 production. We report here (a) that the failure of the R123lo CD4 memory population to respond to anti-CD3/IL-2 stimulation cannot be overcome by addition of anti-CD28, PMA, IL-4 or IL-12, alone or in various combinations, and (b) that this age-dependent subset exhibits impaired production of IL-5 and IL-10 as well as decreased proliferation. R123lo CD4 memory cells from young mice are also deficient in IFN gamma secretion by this subset. Although the R123lo cells respond poorly to receptor-dependent agonists, they can be triggered to proliferate and produce IFN gamma by the combination of PMA and ionomycin. In addition to increasing the proportion of R123lo cells in the memory CD4 pool, aging also leads to a decline in the ability of R123hi cells to produce IL-5 and IL-10. Thus, the accumulation of R123lo cells cannot by itself account for the poor proliferation and Th2 cytokine production of aged T cells in cytokine-supplemented culture conditions.


Emergence of macroscopic directional motion of deformable active cells in confined structures.
There is now growing evidence of collective turbulentlike motion of cells in dense tissues. However, how to control and harness this collective motion is an open question. We investigate the transport of deformable active cells in a periodically asymmetric channel by using a phase-field model. We demonstrate that collective turbulent-like motion of cells can power and steer the macroscopic directional motion through the ratchet channel. The active intercellular forces proportional to the deformation of cells can break thermodynamical equilibrium and induce the directional motion. This directional motion is caused by the ratchet effect rather than the spontaneous symmetry breaking. The motion direction is determined by the asymmetry of the channel. Remarkably, there exits an optimal nonequilibrium driving (depending on the active strength, the elasticity, and the packing fraction) at which the average velocity reaches the maximum. In addition, the optimized packing fraction and the optimized minimum width of the channel can facilitate the directional motion of cells. Our findings are relevant to understanding how macroscopic directional motion relates to the local force transmission mediated by cell-cell contacts in cellular monolayers.


Epithelial estrogen receptor 1 intrinsically mediates squamous differentiation in the mouse vagina.
Estrogen-mediated actions in female reproductive organs are tightly regulated, mainly through estrogen receptor 1 (ESR1). The mouse vaginal epithelium cyclically exhibits cell proliferation and differentiation in response to estrogen and provides a unique model for analyzing the homeostasis of stratified squamous epithelia. To address the role of ESR1-mediated tissue events during homeostasis, we analyzed mice with a vaginal epithelium-specific knockout of Esr1 driven by keratin 5-Cre (K5-Esr1KO). We show here that loss of epithelial ESR1 in the vagina resulted in aberrant epithelial cell proliferation in the suprabasal cell layers and led to failure of keratinized differentiation. Gene expression analysis showed that several known estrogen target genes, including erbB growth factor ligands, were not induced by estrogen in the K5-Esr1KO mouse vagina. Organ culture experiments revealed that the addition of erbB growth factor ligands, such as amphiregulin, could activate keratinized differentiation in the absence of epithelial ESR1. Thus, epithelial ESR1 integrates estrogen and growth factor signaling to mediate regulation of cell proliferation in squamous differentiation, and our results provide new insights into estrogen-mediated homeostasis in female reproductive organs.


Inducible macrophage cytotoxins. II. Tumor lysis mechanism involving target cell-binding proteases.
Thioglycollate-elicited C57BL/6 peritoneal exudate macrophage monolayers (PEMM) stimulated with poly I . poly C or LPS released a macrophage cytotoxin (MCT) that rapidly bound to syngeneic (EL 4) or allogeneic (NS-1, YAC-1) tumor cells but did not bind to normal splenocytes. No binding to human (K562) tumor cells was observed. PEMM stimulated with poly I . poly C destroyed allogeneic tumor cells (NS-1) when separated by cell-impermeable Millipore filters in vitro; in contrast, PEMM not stimulated with poly I . poly C were incapable of lysing targets when separated by membranes. The reversible inhibitors N alpha-p-tosyl-L-arginine methyl ester and soybean trypsin inhibitor and the irreversible inhibitors N alpha-p-tosyl-L-lysine chloromethyl ketone and phenylmethylsulfonyl fluoride, of trypsin-like proteases, significantly or totally inhibited MCT cell-lytic activity for L-929 cells in vitro. Furthermore, modification of MCT-associated arginine residues by 1,2-cyclohexanedione completely blocked lytic activity. MCT was concluded to be an inducible nonspecific cell-lytic effector molecule elaborated by activated macrophages, which could bind to potential target cells, and was itself or was associated with a protease.


Verbalizing facial memory: criterion effects in verbal overshadowing.
This article investigated the role of the recognition criterion in the verbal overshadowing effect (VOE). In 3 experiments, people witnessed an event, verbally described a perpetrator, and then attempted identification. The authors found in Experiment 1, which included a "not present" response option and both perpetrator-present (PP) and perpetrator-absent (PA) lineups, an increased reluctance to identify a person from both lineup types after verbalization. Experiment 2 incorporated a forced-choice procedure, and the authors found no effect of verbalization on identification performance. Experiment 3 replicated the essential aspects of these results. Consequently, the VOE may reflect a change in recognition criterion rather than a changed processing style or alteration of the underlying memory trace. This conclusion was confirmed by computational modeling of the data.


Structure-activity relationships of antibacterial and biocompatible copolymers.
The development of polymers that are both bactericidal and biocompatible would have many applications and are currently of research interest. Following the development of strongly bactericidal copolymers of 4-vinylpyridine and poly(ethylene glycol) methyl ether methacrylate, biocompatibility assays have been completed on these materials to measure their potential biocompatibility. In this article, a new methodology for measuring protein interaction was developed for water-soluble polymers by coupling proteins to surfaces and then measuring the adsorption of copolymers onto these surfaces. Ellipsometry was then used to measure the thickness of adsorbed polymers as a measurement of biocompatibility. These results were then compared and correlated with the results of other biocompatibility assays previously conducted on these polymers, affording a greater understanding of the biocompatibility of the copolymers as well as improving the understanding of the effect of hydrophilic and hydrophobic groups that is vital for the development of these materials.


Mechanism of Endoplasmic Reticulum Stress Pathway in the Osteogenic Phenotypic Transformation of Aortic Valve Interstitial Cells.
Calcific Aortic Valve Disease (CAVD) is a crucial component of degenerative valvular disease in old age and with the increasing prevalence of the aging population. we hope that by modeling valvular osteogenesis and intervening with endoplasmic reticulum stress inhibitor TUDCA to observe the effect of endoplasmic reticulum stress on valve osteogenesis. In this study, rabbit heart valvular interstitial cells (VICs) were isolated and cultured. They treated with ox-LDL (Oxidized Low Density Lipoprotein) stimulation to establish a model of valvular osteogenic transformation. BMP2 (Bone Morphogenetic Protein 2), PERK (Protein kinase R-like endoplasmic reticulum kinase), CHOP (CCAAT/enhancer-binding protein homologous protein) and transcriptional regulatory factor ATF4 (Activating Transcription Factor 4 )were recorded after intervention with ER stress inhibitor TUDCA. The effects of er stress on valvular osteogenic transformation were analyzed. After stimulation of VICs with ox-LDL, the expression levels of BMP2, PERK, CHOP, and ATF4 increased. However, TUDCA treatment can alleviate the increased expression levels of BMP2, PERK ATF4, and CHOP under ox-LDL stimulation to a certain extent. The endoplasmic reticulum stress signaling pathway is involved in ox-LDL-induced calcification of rabbit valve interstitial cells. Inhibition of endoplasmic reticulum stress using TUDCA can improve the progression of rabbit aortic valve calcification.


The effect of film thickness on thermal aerosol generation.
Rapid heating of thin films of pharmaceutical compounds can vaporize the molecules, which leads to formation of aerosol particles of optimal size for pulmonary drug delivery. The aim of this work was to assess the effect of coated film thickness on the purity of a thermally generated (condensation) drug aerosol. Pharmaceuticals in their free base form were spray-coated onto stainless steel foils and subsequently heated and vaporized in airflow via a rapid resistive heating of the foil. Aerosol particles were collected on filters, extracted, and analyzed using reverse phase HPLC to assess the amount of degradation induced during the vaporization process. Condensation aerosols of five pharmaceuticals were formed from a wide range of film coating thicknesses. All five showed a roughly linear trend of increasing aerosol purity with decreasing film thickness, although with quite different slopes. These findings are consistent with a model based on general vaporization and degradation kinetics. Small non-uniformities in the film do not significantly alter aerosol purity. Rapid vaporization of pharmaceuticals coated as thin films on substrates is an efficient way of generating drug aerosols. By controlling the film thickness, the amount of aerosol decomposition can be minimized to produce high purity aerosols.


Invading Escherichia coli Genetics with a Xenobiotic Nucleic Acid Carrying an Acyclic Phosphonate Backbone (ZNA).
A synthetic orthogonal polymer embracing a chiral acyclic-phosphonate backbone [(S)-ZNA] is presented that uniquely adds to the emerging family of xenobiotic nucleic acids (XNAs). (S)-ZNA consists of reiterating six-atom structural units and can be accessed in few synthetic steps from readily available phophonomethylglycerol nucleoside (PMGN) precursors. Comparative thermal stability experiments conducted on homo- and heteroduplexes made of (S)-ZNA are described that evince its high self-hybridization efficiency in contrast to poor binding of natural complements. Although preliminary and not conclusive, circular dichroism data and dynamic modeling computations provide support to a left-handed geometry of double-stranded (S)-ZNA. Nonetheless, PMGN diphosphate monomers were recognized as substrates by Escherichia coli (E. coli) polymerase I as well as being imported into E. coli cells equipped with an algal nucleotide transporter. A further investigation into the in vivo propagation of (S)-ZNA culminated with the demonstration of the first synthetic nucleic acid with an acyclic backbone that can be transliterated to DNA by the E. coli cellular machinery.


Using sexually transmitted disease incidence as a surrogate marker for HIV incidence in prevention trials: a modeling study.
Because many of the sexual behaviors that place individuals at risk of acquiring HIV are the same as those that place them at risk for other sexually transmitted diseases (STDs), researchers and policymakers have called for the use of non-HIV STDs as surrogate markers for HIV infection. This study examined the epidemiologic conditions under which changes in STD incidence are associated with changes in HIV incidence. A mathematical model of HIV/STD transmission was applied to empirical data from a large HIV prevention intervention. The association between participants' HIV infection risk reduction scores and their STD risk reduction scores was measured with use of the Pearson product-moment correlation. The authors examined how the strength of association varied across different epidemiologic parameters and heterosexual behaviors. Moderate to strong associations were noted when the infectivity of the STD was similar to the infectivity of HIV. The association was attenuated for larger STD infectivity values. The prevalence of STD infection was a less important determinant of the strength of association. Stronger associations were obtained when the number of sex partners was large or the number of sex acts was small. Easily transmitted STDs, such as gonorrhea, are unsuitable for general use as surrogate markers for HIV infection. Hepatitis B, syphilis, and chlamydial infection have more promising epidemiologic profiles. Careful studies of STD infectivity are needed to aid in the identification of potential marker STDs.


Scalp HFO rates are higher for larger lesions.
High-frequency oscillations (HFO) in scalp EEG are a new and promising noninvasive epilepsy biomarker, providing added prognostic value, particularly in pediatric lesional epilepsy. However, it is unclear if lesion characteristics, such as lesion volume, depth, type, and localization, impact scalp HFO rates. We analyzed scalp EEG from 13 children and adolescents with focal epilepsy associated with focal cortical dysplasia (FCD), low-grade tumors, or hippocampal sclerosis. We applied a validated automated detector to determine HFO rates in bipolar channels. We identified the lesion characteristics in MRI. Larger lesions defined by MRI volumetric analysis corresponded to higher cumulative scalp HFO rates (P = .01) that were detectable in a higher number of channels (P = .05). Both superficial and deep lesions generated HFO detectable in the scalp EEG. Lesion type (FCD vs tumor) and lobar localization (temporal vs extratemporal) did not affect scalp HFO rates in our study. Our observations support that all lesions may generate HFO detectable in scalp EEG, irrespective of their characteristics, whereas larger epileptogenic lesions generate higher scalp HFO rates over larger areas that are thus more accessible to detection. Our study provides crucial insight into scalp HFO detectability in pediatric lesional epilepsy, facilitating their implementation as an epilepsy biomarker in a clinical setting.


Should all patients with subcentimeter thyroid nodules undergo fine-needle aspiration biopsy and preoperative neck ultrasonography to define the extent of tumor invasion?
Decisions involving the management of patients with papillary microcarcinoma are complex. Here we review and consider the literature in this area including two studies published in this issue of Thyroid. Thyroid nodules 5 mm or smaller have a high rate of false positive ultrasound findings and often yield inadequate cytology on fine needle aspiration biopsy (FNAB). We conclude that nodules of this size with no other clinical findings should not undergo routine FNAB, even if they appear ultrasonographically suspicious. Biopsying such small nodules evokes major patient anxiety and is likely to yield cytology that is insufficient for diagnosis, especially in the hands of inexperienced ultrasonographers. Periodic ultrasound examination, despite its shortcomings, is likely to be a better option for such patients since their small nodules may spontaneously disappear or fail to grow over time. Those that grow by at least 50% or more might be considered for FNAB, but only if they exceed 5 mm.


Fetoscopy in the management of twin pregnancies discordant for a severe abnormality.
Selective feticide by fetoscopic air embolism was carried out in six twin pregnancies complicated by discordance for a severe abnormality. In three, a previous diagnostic fetoscopy had been performed. The procedure was effective and uncomplicated in all cases. One patient is undelivered and five have delivered healthy babies, three at term and two preterm. One of the latter, delivered at 28 weeks, died of complications in the neonatal period.


Stage-adapted treatment of Wegener's granulomatosis. First results of a prospective study.
Considering cyclophosphamide's severe side effects there is a need for a new, less toxic treatment protocol for Wegener's granulomatosis. Here we report the first results of a prospective study using cyclophosphamide pulse therapy (monthly application) (a) as an alternative treatment in seven cases of active generalized Wegener's granulomatosis, which either showed complications under continuous cyclophosphamide treatment or in which the partial remission was not steady, and (b) as the initial treatment in five newly diagnosed patients with active generalized disease. After complete remission had been achieved in all cases in group (a), but only two cases in group (b), we started treatment with trimethoprim/sulfamethoxazole (cotrimoxazole) to maintain remission. Three of 8 patients suffered from severe relapses 9, 11 and 12 months after discontinuation of cyclophosphamide. The 3 patients in group (b) who could not be brought into remission had to be put on continuous cyclophosphamide. In addition, we treated 3 patients with newly diagnosed locoregional disease with cotrimoxazole alone. Two of these patients responded promptly and have only minor symptoms after 13 and 27 months, respectively. In one patient the disease continued to progress in the upper respiratory tract, and treatment was switched to cyclophosphamide and prednisolone after a period of 3 months. From these results we believe that cyclophosphamide pulse therapy is a successful alternative treatment protocol after partial remission has been achieved with a daily administration of cyclophosphamide or if complications, e.g-. leukopenia, arise with the continuous use of this drug. As an initial treatment, however, bolus treatment still appears to be an experimental protocol.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral sinovenous thrombosis as a complication of otitis media.
Otogenic cerebral sinovenous thrombosis (CSVT) is a rare complication of otitis media and associated with significant morbidity and mortality. Classic clinical signs of mastoiditis (pain, swelling, and erythema posterior to the pinna) are not always present at presentation. Treatment of otogenic CSVT consists of conservative surgery, antibiotics, and anticoagulation.


[Mitigated erysipelas after implantation of foreign material].
When an infection occurs in the incisional area following surgery where foreign materials (i. e. endoprostheses, metal plates or plastic meshes) are implanted, a revision may become necessary because an infection in the area of the implant and involvement of the implant itself cannot be ruled out. In the case of a mitigated erysipelas, cultures taken during the revision seldom show bacterial growth. The disease progresses because surgery does not solve the problem of a weakened immune system and lymph stasis; on the contrary, it usually deteriorates the situation. A high dose antibiotic regimen is recommended as therapy for the mitigated erysipelas instead of an operative revision orally given. levofloxacin has proven to be successful reducing the recurrence rate. The course of two patients with mitigated erysipelas is represented for example in form of case studies. The patients were underwent several surgical revisions. But we had not to explant the endoprostheses at all. Finally both patients were treated with levofloxacin without further relapses.


The effectiveness of an educational intervention for sodium restriction in patients with hypertension: study protocol for a randomized controlled trial.
The effectiveness of nonpharmacological interventions in blood pressure reduction has been evidenced by several studies. Nevertheless, as adherence to a low-sodium diet is poor, interventions regarding habit changing should be of a motivational nature in order to develop the ability of overcoming obstacles regarding sodium-restriction behavior. The present study aims to describe the protocol and randomization of a clinical trial design in order to evaluate the effectiveness of an educational intervention based on Dietary Sodium Restriction Questionnaire (DSRQ) scores. The effectiveness measures are the DSRQ score variation and reduction in urinary sodium values from baseline to after 2 and 6 months. This parallel, randomized clinical trial will include 120 participants, recruited and randomized as follows: 60 of them to be allocated to a sodium-restriction educational intervention group whose results are based on the DSRQ application; and the other 60 allocated to a control group with usual care. Educational orientation and usual care sessions will be conducted once a month for a period of 6 months. Both spot urine collection - estimating sodium intake - and the DSRQ will be applied at the baseline, in the eighth week and at the end of the follow-up. There will also be blood collection and 24-h ambulatory blood pressure monitoring (ABPM) at the beginning and end of the follow-up. Anthropometric measurements, blood pressure measurement and 24-h food recall will be collected during follow-up. The study "The effectiveness of an educational intervention to sodium restriction in patients with hypertension" is based on the results of the DSRQ application, whose objective is to evaluate aspects related to nonadherence to the recommendation of a low-sodium diet, identifying adherence barriers and facilitators, contributing to the planning of interventions for improving the adoption of a low-sodium diet and, consequently, hypertension control. ClinicalTrials.gov, Identifier: NCT02848690 . Registered retrospectively on 27 July 2016.


Nonheartbeating cadaveric organ donation.
The authors evaluated the potential use of nonheartbeating (NHB) cadaver donors as an additional source to the current supply of brain-dead cadaver donors. The numbers of cadaveric donors has not increased significantly during the last 5 years, despite a rising need for transplantable organs. Any improvement in cadaveric organ procurement will depend on the use of previously unrecognized potential donors. During a 2-year period, 24 kidneys were retrieved from 12 NHB donors. Nineteen kidneys were transplanted. These kidneys sustained a mean warm ischemia time of 26 minutes (range 20-35 min). A mean lowest creatinine level of 2.0 mg/dL, (range 1.1-3.0 mg/dL), the rate of postoperative dialysis (22%), and a 1-year graft survival rate of 76% for kidneys from NHB-donated kidneys compare favorably to expected results achieved nationally from brain-dead cadaveric donors. Nonheartbeating donor kidneys can yield acceptable graft function and be of no disadvantage to recipients of cadaver transplants.


Tissue dissection before direct manipulation to the pathology with pulsed laser-induced liquid jet system in skull base surgery--preservation of fine vessels and maintained optic nerve function.
Most difficulties in skull base tumor removal are generally caused by adhesion of feeding arteries to the vital structures and cranial nerves. Water jet technology provides tissue dissectability with preservation of fine blood vessels both in experimental and clinical situations. However problems still remain regarding whether tumor removal with preservation of peripheral nerve function is possible or not. This clinical investigation evaluated functional preservation of peripheral nerves and dissectability with a newly developed pulsed laser-induced liquid jet (LILJ) system under intraoperative electrophysiological monitoring. The LILJ system was used to treat 21 patients with skull base tumors manifesting as severe visual disturbance through the extended transsphenoidal approach. The LILJ system consists of a bayonet-shaped catheter incorporating a jet generator, and total weight is around 7 g. Intraoperative visual evoked potential (VEP), and pre/postoperative conventional visual assessments were investigated. Precise dissections of the tumor were obtained, resulting in gross total removal in 19 of 21 patients. Two patients with meningiomas with tight adhesion to the origin of the lenticulostriate arteries had small remnants. Of the 21 patients, 16 showed immediate improvement on intraoperative VEP, 2 had no change, and 3 had prolonged latency, which required intermittent suspension of procedure. A total of 20 patients and 40 eyes showed good recovery at discharge, and all patients evaluated had recovered good visual status. The LILJ system can achieve safe and optimal removal with functional preservation of optic nerves, probably because of the high resistance of the arachnoidal sheath and fine vascular tissue.


An enhancer-blocking element between alpha and delta gene segments within the human T cell receptor alpha/delta locus.
T cell receptor (TCR) alpha and delta gene segments are organized within a single genetic locus but are differentially regulated during T cell development. An enhancer-blocking element (BEAD-1, for blocking element alpha/delta 1) was localized to a 2.0-kb region 3' of TCR delta gene segments and 5' of TCR alpha joining gene segments within this locus. BEAD-1 blocked the ability of the TCR delta enhancer (Edelta) to activate a promoter when located between the two in a chromatin-integrated construct. We propose that BEAD-1 functions as a boundary that separates the TCR alpha/delta locus into distinct regulatory domains controlled by Edelta and the TCR alpha enhancer, and that it prevents Edelta from opening the chromatin of the TCR alpha joining gene segments for VDJ recombination at an early stage of T cell development.


Aspergillus fumigatus RasA regulates asexual development and cell wall integrity.
The Ras family of proteins is a large group of monomeric GTPases. Members of the fungal Ras family act as molecular switches that transduce signals from the outside of the cell to signaling cascades inside the cell. A. fumigatus RasA is 94% identical to the essential RasA gene of Aspergillus nidulans and is the Ras family member sharing the highest identity to Ras homologs studied in many other fungi. In this study, we report that rasA is not essential in A. fumigatus, but its absence is associated with slowed germination and a severe defect in radial growth. The DeltarasA hyphae were more than two times the diameter of wild-type hyphae, and they displayed repeated changes in the axis of polarity during hyphal growth. The deformed hyphae accumulated numerous nuclei within each hyphal compartment. The DeltarasA mutant conidiated poorly, but this phenotype could be ameliorated by growth on osmotically stabilized media. The DeltarasA mutant also showed increased susceptibility to cell wall stressors, stained more intensely with calcofluor white, and was refractory to lysing enzymes used to make protoplasts, suggesting an alteration of the cell wall. All phenotypes associated with deletion of rasA could be corrected by reinsertion of the wild-type gene. These data demonstrate a crucial role for RasA in both hyphal growth and asexual development in A. fumigatus and provide evidence that RasA function is linked to cell wall integrity.


Nursing activities at clinics in rural areas in Japan: gaps between recognition of importance and implementation.
This study determined the level of implementation and the importance placed on various nursing activities at clinics in rural areas of Japan in order to explore the achievement and perceived importance of implementing certain nursing roles and activities at such clinics. To identify these items, a questionnaire was administered to 40 nurses working in rural clinics. The results showed that activities related to "Basic Nursing Practice" and "Community Understanding" were recognized as important and were performed by almost all nurses. Some activities related to "Administration and Operation" and "Cooperation with Local Government" were recognized as important, but were not implemented, thereby hampering the continuum of care across the health system. These activities, which are related to collaboration with hospitals and local governments that support the clinics, included adjustment of staff inside and outside the facilities to guarantee the use of paid holidays, as well as collaboration with acute care, remote medical systems, and local governments during emergencies and for disaster preparation. Additional support for nurses in collaboration between clinics in rural areas, hospitals, and regional administrations that support the clinics remains a challenge to be addressed.


Comparison of Intradialytic Parenteral Nutrition with Glucose or Amino Acid Mixtures in Maintenance Hemodialysis Patients.
Many long-term maintenance hemodialysis patients have symptoms of protein-energy wasting caused by malnutrition. Each session of hemodialysis removes about 10 to 12 g of amino acids and 200 to 480 kcal of energy. Patients receiving hemodialysis for chronic kidney disease may be undernourished for energy, protein consumption, or both. Non-diabetic hemodialysis patients were randomized to three treatment groups: oral supplementation, oral supplementation plus high-concentration glucose solution (250 mL containing 50% glucose) and these two interventions plus 8.5% amino acids solution. The post-treatment energy status of the glucose group was significantly higher than its baseline level, whereas the control group's status was significantly lower. The glucose group had significantly higher concentrations of asparagine, glutamine, glycine, alanine, and lysine after treatment. All treatment groups had significantly increased hemoglobin levels but significantly decreased transferrin levels after treatment compared to baseline. After treatment, the amino acid group had significantly higher albumin level compared to the glucose group (p = 0.001) and significantly higher prealbumin level compared to the control group (p = 0.017). In conclusion, long-term intervention with high-concentration glucose solution at each hemodialysis session is a simple and cheap method that replenished energy stores lost during hemodialysis of non-diabetic patients.


Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for cancer therapy.
Based on the remodeling of glycosphingolipids on the human tumor cell lines with manipulation of glycosyltransferase genes, roles of sugar moieties in tumor-associated carbohydrate antigens have been analyzed. Two main topics, that is, the roles of ganglioside GD3 in human malignant melanomas and those of GD2 in small cell lung cancer (SCLC) were reported. GD3 enhances tyrosine phosphorylation of two adaptor molecules, p130Cas and paxillin, resulting in the increased cell growth and invasion in melanoma cells. GD2 also enhances the proliferation and invasion of SCLC cells. GD2 also mediates apoptosis with anti-GD2 monoclonal antibodies (mAbs) via dephosphorylation of the focal adhesion kinase. These approaches have promoted further understanding of mechanisms by which gangliosides modulate malignant properties of human cancer, and the results obtained here propose novel targets for cancer therapy.


Determination of elastic moduli of elastic-plastic microspherical materials using nanoindentation simulation without mechanical polishing.
When using the Oliver-Pharr method, the indented specimen is assumed to be a perfectly flat surface, thus ignoring the influences of surface roughness that might be encountered in experiment. For nanoindentation measurements, a flat surface is fabricated from curved specimens by mechanical polishing. However, the position of the polished curved surface cannot be controlled. There are no reliable theoretical or experimental methods to evaluate the mechanical behavior during nanoindentation of an elastic-plastic microsphere. Therefore, it is necessary to conduct reliable numerical simulations to evaluate this behavior. This article reports a systematic computational study regarding the instrumented nanoindentation of elastic-plastic microspherical materials. The ratio between elastic modulus of the microsphere and the initial yield stress of the microsphere was systematically varied from 10 to 1000 to cover the mechanical properties of most materials encountered in engineering. The simulated results indicate that contact height is unsuitable to replace contact depth for obtaining the indentation elastic modulus of microspherical materials. The extracted elastic modulus of a microsphere using the Oliver-Pharr method with the simulated unloading curve depends on the indentation depth. It demonstrates that nanoindentation on microspherical materials exhibits a "size effect".


Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.
Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.


Trends in epidemiology and risk factors of opportunistic infections in kidney transplant recipients between 2004-2022.
While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known. Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models. After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially CMV syndromes and diseases (213/544, 39%). A third of the infected patients experienced at least 2 opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than afterwards (34.7 infections for 100 patient-years vs. 3.64). Opportunistic infections associated with the age of the donor (p = 0.032), the age of the recipient (p = 0.049), the CMV serostatus (p < 10-6), a higher class II HLA mismatch (p = 0.032), and an induction treatment including rabbit anti-thymocyte globulins (p = 0.026). Repeated opportunistic infections associated with each other (p < 10-6) and with renal death (p < 10-6). Opportunistic infections occur with a 2-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome.


Prolonged analgesia with liposomal bupivacaine in a mouse model.
Currently available local anesthetics have relatively limited duration of action and some may cause severe systemic toxicity. An ultralong lasting local anesthetic would be useful to produce prolonged intraoperative anesthesia and extended postoperative analgesia. The goal of this study was to synthesize a sustained release local anesthetic formulation that would produce prolonged sensory block and decrease the possibility of systemic toxicity. The effect of liposomes containing 1.1% bupivacaine on duration of sensory block of the mouse tail was compared with equivalent concentrations of bupivacaine with and without epinephrine. Analgesia was assessed using the tail flick test. Systemic toxicity (LD50) was assessed after intraperitoneal injection and in vitro release rates were compared by dialysis technique for liposomal and plain bupivacaine. Sensory block was significantly prolonged with liposomal bupivacaine (130 +/- 38 minutes) compared to plain bupivacaine (46 +/- 11 minutes, P < .01) or bupivacaine with epinephrine (81 +/- 28 minutes, P < .05). The LD50 was significantly lower for plain bupivacaine (61 mg/kg, 95% confidence intervals 47-79) than for liposomal bupivacaine (291 mg/kg, 95% confidence intervals 201-422). The time to 50% in vitro release through a dialysis membrane for liposomal bupivacaine (28 +/- 9 minutes) was markedly prolonged compared to plain bupivacaine (7 +/- 1 minutes). This study shows that liposomal encapsulation of bupivacaine significantly prolongs duration of action and greatly decreases systemic toxicity of the drug. These findings may be promising for the future production of formulations of ultralong lasting local anesthetics with enhanced efficacy and safety.


Co-transplantation of Epidermal Neural Crest Stem Cells and Olfactory Ensheathing Cells Repairs Sciatic Nerve Defects in Rats.
Cell-based therapy is an alternative strategy to improve outcomes of peripheral nerve injury (PNI). Epidermal neural crest stem cell (EPI-NCSC) is obtained from autologous tissue without immunological rejection, which could expand quickly in vitro and is suitable candidate for cell-based therapy. Olfactory ensheathing cell (OEC) could secrete multiple neurotrophic factors (NTFs), which is often used to repair PNI individually. However, whether the combination of EPI-NCSC and OEC have better effects on PNI repair remains unclear. Here we use EPI-NCSC and OEC co-transplantation in a rat sciatic nerve defect model to ascertain the effects and potential mechanisms of cells co-transplantation on PNI. The effect of EPI-NCSC and OEC co-transplantation on PNI is assessed by using a combination of immunohistochemistry (IHC), electrophysiological recording and neural function test. Co-transplantation of EPI-NCSC and OEC exerts a beneficial effect upon PNI such as better organized structure, nerve function recovery, and lower motoneuron apoptosis. IHC and enzyme-linked immuno sorbent assay (ELISA) further demonstrate that cells co-transplantation may improve PNI via the expression of brain derived growth factor (BDNF) and nerve growth factor (NGF) up-regulated by EPI-NCSC and OEC synergistically. Eventually, the results from this study reveal that EPI-NCSC and OEC co-transplantation effectively repairs PNI through enhancing the level of BDNF and NGF, indicating that cells co-transplantation may serve as a fruitful avenue for PNI in clinic treatment.


A 20-Country Comparative Assessment of the Effectiveness of Nutri-Score vs. NutrInform Battery Front-of-Pack Nutritional Labels on Consumer Subjective Understanding and Liking.
The incidence of overweight and obesity has generated significant concerns among European consumers and institutions. As part of a set of measures undertaken, the European Union (EU) called for one harmonized mandatory front-of-pack nutritional label (FOPL) to improve consumer food nutritional knowledge and encourage healthier and more informed food choices. Different types of FOPLs, ranging from nutrient-specific labels-such as the NutrInform Battery-to summary labels-such as the Nutri-Score-have been developed and introduced in different markets, reporting different degrees of effectiveness in terms of understanding. The aim of this study is to provide actionable insights by analyzing a specific part of the complex consumers' decision-making process in food when aided by FOPLs. Adopting a between-subject experiment on a sample of 4560 respondents in 20 EU member countries, the study compares the consumer subjective understanding and liking of two labels currently under examination by the EU bodies, the NutrInform Battery and the Nutri-Score. At an aggregated level, the results show that NutrInform Battery is more effective than Nutri-Score in improving consumer subjective understanding and leads to a higher liking towards the label. A detailed by-country analysis highlights either a superiority or a parity of NutrInform Battery for subjective understanding and liking. Theoretically, this study, through a large panel of respondents, adds the fundamental perspective on subjective understanding, complementing the findings of extant research on objective understanding, and further clarifies the role of liking as a complementary element in the food decision-making process toward heathier and more informed food choices. This might be of significant relevance in providing additional evidence that can be used by policymakers in their attempt toward the selection of a uniform FOPL at EU level.


[MR angiography of pelvic veins and the inferior vena cava using 0.5 tesla].
The pelvic veins and/or the inferior vena cava were examined in 15 patients with pelvic vein thrombosis or retroperitoneal tumours, using phlebography or cavography and MR angiography. The latter was carried out using 0.5 Tesla with an inflow technique TR/TE 30/8 ms, flip angle 70 degrees). 3-D projection angiograms were obtained from the 2-D angiograms in the coronary plane. Image quality was generally satisfactory and the veins up to the internal iliac could be demonstrated in all cases; below this, the examination was unreliable. Comparison of the methods with reference to information of therapeutic relevance has shown that in two-thirds of all examinations (8/13) MR angiography and phlebography were of equal diagnostic value. In the presence of a renal cell carcinoma, MR angiography was unable to distinguish between thrombosis and infiltration of the vena cava.


Respiratory health among bleachery workers exposed to ozone and chlorine dioxide.
This study investigated the possibility of occupational exposure to ozone increasing the risk of obstructive airway disease among bleachery workers. : Bleachery workers (N = 129) from two Swedish pulp mills using ozone for bleaching were studied together with referents (N = 80) from adjacent paper mills. The pulp mills had previously used chlorine dioxide as the bleaching agent. Testings included spirometry, methacholine challenge testing, and questionnaires. Area samplings showed sporadic ozone levels exceeding 0.9 ppm. There was a greater prevalence of wheezing (25%) among the bleachery workers with a history of gassings (from ozone, chlorine, or sulfur dioxide) than among those without gassings (18%) and among the referents (13%). Among the current smokers the fraction with a slightly increased bronchial responsiveness to methacholine was greater among the bleachery workers reporting gassings than among those that had not been gassed. For the period from 1992 to 1996, when the mills were using ozone, there was an increased incidence rate of wheezing among the workers in the bleachery (incidence rate ratio 2.3, 95% confidence interval 1.6-5.8). Repeated exposure to irritants increases the risk of asthma-like symptoms. This finding reinforces the view that repeated peak exposures to irritants must be prevented in pulp mills.


Development of autoimmune hemolytic anemia during the treatment of a patient with acute myelomonocytic leukemia.
Drug induced autoimmune hemolytic anemia is a well-known complication of drug therapy but it is often misdiagnosed. Drug induced autoimmune hemolytic anemia is difficult to differantiate from classical autoimmune hemolytic anemia. Here, we have reported a case with autoimmune hemolytic anemia might be caused by drugs such as teicoplanin, imipenem and amphotericin B. In our case, on the fifteenth postadmission day was occur autoimmune hemolytic anemia. At this while, chemotherapy of patient had been completed and the patient have been taking antibiotherapy which include teicoplanin, imipenem and amphotericin B. Antibiotherapy could not be stopped because of febrile neutropenia. Symptoms and sings of anemia improved with prednisolon therapy. Suspicious drug must be stopped in drug induced autoimmune hemolytic anemia but in the conditions that drug could not be stopped, steroid treatment can be used in the treatment of hemolytic anemia.


The Time Course of Audio-Visual Phoneme Identification: a High Temporal Resolution Study.
Speech unfolds in time and, as a consequence, its perception requires temporal integration. Yet, studies addressing audio-visual speech processing have often overlooked this temporal aspect. Here, we address the temporal course of audio-visual speech processing in a phoneme identification task using a Gating paradigm. We created disyllabic Spanish word-like utterances (e.g., /pafa/, /paθa/, …) from high-speed camera recordings. The stimuli differed only in the middle consonant (/f/, /θ/, /s/, /r/, /g/), which varied in visual and auditory saliency. As in classical Gating tasks, the utterances were presented in fragments of increasing length (gates), here in 10 ms steps, for identification and confidence ratings. We measured correct identification as a function of time (at each gate) for each critical consonant in audio, visual and audio-visual conditions, and computed the Identification Point and Recognition Point scores. The results revealed that audio-visual identification is a time-varying process that depends on the relative strength of each modality (i.e., saliency). In some cases, audio-visual identification followed the pattern of one dominant modality (either A or V), when that modality was very salient. In other cases, both modalities contributed to identification, hence resulting in audio-visual advantage or interference with respect to unimodal conditions. Both unimodal dominance and audio-visual interaction patterns may arise within the course of identification of the same utterance, at different times. The outcome of this study suggests that audio-visual speech integration models should take into account the time-varying nature of visual and auditory saliency.


Expression of microtubule-associated protein 2 by reactive astrocytes.
After an injury to the central nervous system, a dramatic change in the astrocytes bordering the wound occurs. The most characteristic feature of this process, termed reactive gliosis, is the upregulation of the intermediate filament protein, glial fibrillary acidic protein. In the present study, we show that reactive astrocytes express high levels of microtubule-associated protein 2 (MAP-2), a protein normally found in the somatodendritic compartment of neurons. When sections of injured brain are double-stained with antibodies directed against MAP-2 and glial fibrillary protein, all of the reactive astrocytes are found to contain MAP-2. The high levels of this protein appear to represent a permanent change in reactive astrocytes. In parallel quantitative studies, an elevated level of MAP-2 in the injured brain is confirmed by an immunoblot analysis of injured and normal white matter. This report demonstrates the direct involvement of a microtubule protein in the process of reactive gliosis.


Effect of 12-hydroxyeicosatetraenoic acid on cytosolic calcium in human neutrophils.
12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) has been reported to be a chemoattractant for human neutrophils. To assess its cellular mechanism, we focused on the effect of 12-HETE on cytosolic Ca2+ ([Ca2+]i) and characterized the effect of 12-HETE on [Ca2+]i in human neutrophils. 12(S)- and 12(R)-HETE increased [Ca2+]i in the presence and absence of extracellular Ca2+ in a concentration-related fashion. The elevation of [Ca2+]i by 12(R)-HETE was completely abolished by pertussis toxin treatment. U-73122, a selective phospholipase C inhibitor, depressed the 12(S)- and 12(R)-HETE-induced rise in [Ca2+]i in the presence and absence of extracellular Ca2+. 12(R)-HETE resulted in the rapid production of inositol 1,4,5-trisphosphate (IP3). Furthermore, 12(R)-HETE elicited slight depolarization of neutrophils as assessed using the fluorescent dye bis-oxonol. These results provide evidence demonstrating the signal transduction pathway in human neutrophils after stimulation with 12-HETE and suggest that 12-HETE causes a rapid rise of [Ca2+]i by mobilizing Ca2+ from an IP3-sensitive intracellular Ca2+ pool in human neutrophils.


A cross-sectional study of the relationship between reported human papillomavirus vaccine exposure and the incidence of reported asthma in the United States.
Asthma is a chronic disorder that affects persons of all ages impacting the quality of their lives. This cross-sectional hypothesis-testing study evaluated the relationship between human papillomavirus vaccine and the risk of an incident asthma diagnosis in a defined temporal period post-vaccination. The 2015-2016 National Health and Nutrition Examination Survey data were examined for a group of 60,934,237 weighted persons between 9 and 26 years old in Statistical Analysis Software. Reported incident asthma significantly clustered in the year of reported human papillomavirus vaccination. When the data were separated by gender, the effects observed remained significant for males but not females. The results suggest that human papillomavirus vaccination resulted in an excess of 261,475 asthma cases with an estimated direct excess lifetime cost of such persons being US$42 billion. However, it is unclear what part of the vaccine and/or vaccine medium may have increased an individual's susceptibility to an asthma episode, whether the asthma diagnosis represented one asthma episode or if it is chronic, and how much therapeutic support was needed (if any) and for how long, which would impact cost. Despite the negative findings in this study, routine vaccination is an important public health tool, and the results observed need to be viewed in this context.


Evaluation of the Quadri-Planes Method in Computer-Aided Diagnosis of Breast Lesions by Ultrasonography: Prospective Single-Center Study.
Computer-aided diagnosis (CAD) is a tool that can help radiologists diagnose breast lesions by ultrasonography. Previous studies have demonstrated that CAD can help reduce the incidence of missed diagnoses by radiologists. However, the optimal method to apply CAD to breast lesions using diagnostic planes has not been assessed. The aim of this study was to compare the performance of radiologists with different levels of experience when using CAD with the quadri-planes method to detect breast tumors. From November 2018 to October 2019, we enrolled patients in the study who had a breast mass as their most prominent symptom. We assigned 2 ultrasound radiologists (with 1 and 5 years of experience, respectively) to read breast ultrasonography images without CAD and then to perform a second reading while applying CAD with the quadri-planes method. We then compared the diagnostic performance of the readers for the 2 readings (without and with CAD). The McNemar test for paired data was used for statistical analysis. A total of 331 patients were included in this study (mean age 43.88 years, range 17-70, SD 12.10), including 512 lesions (mean diameter 1.85 centimeters, SD 1.19; range 0.26-9.5); 200/512 (39.1%) were malignant, and 312/512 (60.9%) were benign. For CAD, the area under the receiver operating characteristic curve (AUC) improved significantly from 0.76 (95% CI 0.71-0.79) with the cross-planes method to 0.84 (95% CI 0.80-0.88; P<.001) with the quadri-planes method. For the novice reader, the AUC significantly improved from 0.73 (95% CI 0.69-0.78) for the without-CAD mode to 0.83 (95% CI 0.80-0.87; P<.001) for the combined-CAD mode with the quadri-planes method. For the experienced reader, the AUC improved from 0.85 (95% CI 0.81-0.88) to 0.87 (95% CI 0.84-0.91; P=.15). The kappa indicating consistency between the experienced reader and the novice reader for the combined-CAD mode was 0.63. For the novice reader, the sensitivity significantly improved from 60.0% for the without-CAD mode to 79.0% for the combined-CAD mode (P=.004). The specificity, negative predictive value, positive predictive value, and accuracy improved from 84.9% to 87.8% (P=.53), 76.8% to 86.7% (P=.07), 71.9% to 80.6% (P=.13), and 75.2% to 84.4% (P=.12), respectively. For the experienced reader, the sensitivity improved significantly from 76.0% for the without-CAD mode to 87.0% for the combined-CAD mode (P=.045). The NPV and accuracy moderately improved from 85.8% and 86.3% to 91.0% (P=.27) and 87.0% (P=.84), respectively. The specificity and positive predictive value decreased from 87.4% to 81.3% (P=.25) and from 87.2% to 93.0% (P=.16), respectively. S-Detect is a feasible diagnostic tool that can improve the sensitivity, accuracy, and AUC of the quadri-planes method for both novice and experienced readers while also improving the specificity for the novice reader. It demonstrates important application value in the clinical diagnosis of breast cancer. ChiCTR.org.cn 1800019649; http://www.chictr.org.cn/showproj.aspx?proj=33094.


A combination therapy including psyllium and plant sterols lowers LDL cholesterol by modifying lipoprotein metabolism in hypercholesterolemic individuals.
We conducted a randomized, double blind, crossover, placebo-controlled study to determine the effects of a combination therapy including plant sterols (PS) and psyllium (PSY), provided via cookies, on plasma lipids and on the size and subfraction distribution of VLDL, LDL, and HDL. Thirty-three healthy free-living individuals (11 males and 22 females), aged 35-65 y, with a BMI between 25 and 35 kg/m(2) and initial plasma LDL cholesterol (LDL-C) concentrations between 2.6 and 4.1 mmol/L (100 and 160 mg/dL), were randomly assigned to receive treatment cookies (7.68 g/d PSY and 2.6 g/d PS) or placebo cookies (0 g PSY+PS) for 4 wk. After a 3-wk washout period, subjects received the other cookies for an additional 4 wk. Plasma total cholesterol concentrations were significantly reduced for all subjects, from 5.65 +/- 0.72 mmol/L after the placebo period to 5.28 +/- 0.76 mmol/L after the PSY+PS cookie period (P < 0.01). These reductions were primarily in LDL-C, which decreased from 3.48 +/- 0.70 to 3.14 +/- 0.78 mmol/L after PSY+PS cookie consumption (P < 0.01). Intake of the PSY+PS cookie decreased the number of intermediate density lipoprotein (IDL), LDL, and HDL particles (P < 0.05) and plasma apo B concentrations (P < 0.01). The decreases in LDL and HDL particles were in the small subfractions. Because smaller LDL particles are associated with an increased risk of heart disease and because smaller HDL particles are indicative of diminished reverse cholesterol transport, we conclude that the combination therapy resulted in a less atherogenic lipoprotein profile. In addition, the evaluation of lipoprotein subfractions resulting from the action of the fiber and plant sterols in the intestinal lumen provides an insight on the secondary mechanisms of plasma LDL-C lowering.


Femtosecond laser-assisted astigmatic keratotomy: a review.
Astigmatic keratotomy (AK) remains an accessible means to correct surgically induced or naturally occurring astigmatism. The advantages of femtosecond laser-assisted astigmatic keratotomy (FSAK) over conventional methods have been recognized recently. This review evaluates the efficacy, complications, and different methods of FSAK for correction of astigmatism in native eyes and those that underwent previous penetrating keratoplasty (PKP).The penetrating and intrastromal FSAK (IFSAK) techniques can reduce post-keratoplasty astigmatism by 35.4% to 84.77% and 23.53% to 89.42%, respectively. In native eyes, the penetrating and IFSAK techniques reduce astigmatism by 26.8% to 58.62% and 36.3% to 58% respectively, implying that the magnitude of the astigmatic reduction is comparable between the two FSAK procedures. Nonetheless, IFSAK offers the additional advantages of almost no risk of infection, wound gape, and epithelial ingrowth. The use of nomograms, anterior-segment optical coherence tomography, and consideration of posterior cornea and corneal biomechanics are helpful to enhance the efficacy and safety of FSAK. The complications of FSAK in eyes that underwent PKP include overcorrection, visual loss, microperforations, infectious keratitis, allograft rejection, and endophthalmitis. The reported difficulties in native eyes include overcorrection, anterior gas breakthrough, and suction loss. In eyes that underwent PKP, FSAK effectively reduces high regular or irregular astigmatism, with rare and manageable complications. Nevertheless, the drawbacks of the procedure include the potential loss of visual acuity and low predictability. For native eyes undergoing femtosecond laser-assisted cataract surgery, IFSAK is a good choice to correct low astigmatism (< 1.5 diopters). The refractive effect of astigmatism from the posterior cornea needs to be considered in the nomograms for native eyes undergoing refractive cataract surgery. To further improve the efficacy of FSAK, more large-scale randomized studies with longer follow-up are needed.


Eplerenone repolarizes muscle membrane through Na,K-ATPase activation by Tyr10 dephosphorylation.
Eplerenone, an aldosterone antagonist, repolarizes muscle membrane in-vitro and increases strength in-vivo in channelopathies. In Duchenne dystrophy, it is administered for cardiomyopathy. We studied its mechanism of action on skeletal muscle to test its suitability for increasing strength in Duchenne dystrophy. Using membrane potential measurements, quantitative PCR, ELISA, and Western blots, we examined the effects of eplerenone on skeletal muscle Na,K-ATPase. The repolarizing effect of eplerenone in muscle fibres was counteracted by oubain, an ATPase blocker. In our experiment, ATPA1A mRNA and total ATPase protein were not elevated. Instead, Tyr10 of the α1 subunit was dephosphorylated which would agree with ATPase activation. Dephosporylation of the coupled Akt kinase corroborated our findings. We conclude that eplerenone repolarizes muscle membrane by Na,K-ATPase activation by dephosphorylation at Tyr10. Since ATPase protein is known to be compensatorily increased in Duchenne patients without activity change, eplerenone treatment may be beneficial.


Zooplankton as a potential vector for white band disease transmission in the endangered coral, Acropora cervicornis.
Coral diseases are a leading factor contributing to the global decline of coral reefs, and yet mechanisms of disease transmission remain poorly understood. This study tested whether zooplankton can act as a vector for white band disease (WBD) in Acropora cervicornis. Natural zooplankton communities were collected from a coral reef in Bocas del Toro, Panama. Half of the zooplankton were treated with antibiotics for 24 h after which the antibiotic-treated and non-antibiotic-treated zooplankton were incubated with either seawater or tissue homogenates from corals exhibiting WBD-like symptoms. A total of 15 of the 30 asymptomatic A. cervicornis colonies exposed to zooplankton incubated in disease homogenate in tank-based experiments showed signs of WBD, regardless of prior antibiotic incubation. These results indicate that in our experimental conditions zooplankton were a vector for coral disease after exposure to disease-causing pathogens. Given the importance of heterotrophy on zooplankton to coral nutrition, this potential mode of disease transmission warrants further investigation.


[Resting state fMRI study of emotional network in patients with postconcussion syndrome].
Objective: To discuss functional connectivity changes in the emotional network of patients with post-concussion syndrome (PCS) and their clinical significance by resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Twenty-seven patients with PCS were recruited from the Department of Neurosurgery of Anhui provincial hospital affiliated to Anhui medical university from October 2015 to April 2016, and 27 healthy subjects were recruited as the controls. The Hamilton Anxiety Scale (HAMA) and The Hamilton Depression Scale (HAMD) were used to evaluate the emotional state of two groups of subjects. All fMRI data were preprocessed after RS-fMRI scanning, the left and right amygdala were selected as region of interest (ROI) to make functional connectivity (FC) calculation with the whole brain and then the results were did statistical analysis in order to obtain the altered brain areas of amygdala and whole brain functional connectivity in the PCS patient, to understand the functional changes of emotional network. Results: HAMA and HAMD scores of PCS group and the health controls had significant statistical difference (HAMA: the PCS group 9.8±1.5, the health controls 4.5±1.2, P=0.044; HAMD: the PCS group 12±1.2, the health controls was 4.2±1.5, P=0.024). Compared with the health controls, the left amygdala in PCS patients showed decreased FC with left insula, left putamen, left anterior cingulate gyrus, left inferior orbital frontal gyrus, left medial superior frontal gyrus, bilateral superior temporal gyrus, left superior temporal pole, bilateral supramarginal gyrus et al, on the contrary with the increased FC with right superior orbital frontal gyrus, right middle frontal lobe, right orbital frontal lobe, right middle frontal gyrus. The right amygdala in PCS patients showed decreased FC with bilateral putamen, right inferior orbital frontal gyrus, left insula, bilateral precuneus, bilateral superior temporal pole, right superior temporal gyrus, right supramarginal gyrus et al. Similarly, it had the increased FC with the left middle occipital lobe and the left superior occipital lobe. Conclusion: Abnormal emotional network function of PCS patients in resting state, which may be one of the reasons that lead to emotional and cognitive dysfunction in PCS patients.


The multiple roles of histidine in protein interactions.
Among the 20 natural amino acids histidine is the most active and versatile member that plays the multiple roles in protein interactions, often the key residue in enzyme catalytic reactions. A theoretical and comprehensive study on the structural features and interaction properties of histidine is certainly helpful. Four interaction types of histidine are quantitatively calculated, including: (1) Cation-π interactions, in which the histidine acts as the aromatic π-motif in neutral form (His), or plays the cation role in protonated form (His+); (2) π-π stacking interactions between histidine and other aromatic amino acids; (3) Hydrogen-π interactions between histidine and other aromatic amino acids; (4) Coordinate interactions between histidine and metallic cations. The energies of π-π stacking interactions and hydrogen-π interactions are calculated using CCSD/6-31+G(d,p). The energies of cation-π interactions and coordinate interactions are calculated using B3LYP/6-31+G(d,p) method and adjusted by empirical method for dispersion energy. The coordinate interactions between histidine and metallic cations are the strongest one acting in broad range, followed by the cation-π, hydrogen-π, and π-π stacking interactions. When the histidine is in neutral form, the cation-π interactions are attractive; when it is protonated (His+), the interactions turn to repulsive. The two protonation forms (and pKa values) of histidine are reversibly switched by the attractive and repulsive cation-π interactions. In proteins the π-π stacking interaction between neutral histidine and aromatic amino acids (Phe, Tyr, Trp) are in the range from -3.0 to -4.0 kcal/mol, significantly larger than the van der Waals energies.


Hepatoblastoma in the neonatal period: An unusual presentation.
Hepatoblastoma (HBL) is a rare primary malignant liver tumor affecting mainly pediatric patients in the age group 6 months to 3 years. Presentation of HBL in the neonatal period is rare. HBL can be diagnosed on cytology along with subtyping. Estimation of serum alpha-fetoprotein (AFP) is essential as a tumor marker. Fetal type HBL usually shows high AFP level. In this report, diagnosis of HBL in a 10-day-old baby with low serum AFP is being described for its unusual presentation.


Hibernating squirrel muscle activates the endurance exercise pathway despite prolonged immobilization.
Skeletal muscle atrophy is a very common clinical challenge in many disuse conditions. Maintenance of muscle mass is crucial to combat debilitating functional consequences evoked from these clinical conditions. In contrast, hibernation represents a physiological state in which there is natural protection against disuse atrophy despite prolonged periods of immobilization and lack of nutrient intake. Even though peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1-α (PGC-1α) is a central mediator in muscle remodeling pathways, its role in the preservation of skeletal muscle mass during hibernation remains unclear. Since PGC-1α regulates muscle fiber type formation and mitochondrial biogenesis, we analyzed muscles of 13-lined ground squirrels. We find that animals in torpor exhibit a shift to slow-twitch Type I muscle fibers. This switch is accompanied by activation of the PGC-1α-mediated endurance exercise pathway. In addition, we observe increased antioxidant capacity without evidence of oxidative stress, a marked decline in apoptotic susceptibility, and enhanced mitochondrial abundance and metabolism. These results show that activation of the endurance exercise pathway can be achieved in vivo despite prolonged periods of immobilization, and therefore might be an important mechanism for skeletal muscle preservation during hibernation. This PGC-1α regulated pathway may be a potential therapeutic target promoting skeletal muscle homeostasis and oxidative balance to prevent muscle loss in a variety of inherited and acquired neuromuscular disease conditions.


Mechanism of inhibition of herpes simplex virus replication by delta 7-prostaglandin A1 and delta 12-prostaglandin J2.
We studied the effect of prostaglandins (PGs) A1, delta 7-A1, A2, D2, E1, E2, F2 alpha, J2 and delta 12-J2 on the replication of herpes simplex virus type 2 (HSV-2). Of nine PGs we tested, delta 7-PGA1 was found to have the most potent inhibitory effect; 50% inhibitory dose (ID50) was 0.35 microgram/ml in the plaque reduction assays and HSV-2 induced protein synthesis was strongly suppressed at 0.5 microgram/ml whereas at this dose, the protein synthesis of uninfected cells was not inhibited. Dot blot hybridization analysis revealed that delta 7-PGA1 and delta 12-PGJ2 inhibited the primary transcription of HSV-2. Thus we suggest that those PGs are primarily active at the level of mRNA synthesis.


[Transplantation of pedicled gastric wall flaps to the intestines in Wistar rats].
The pedicled gastric wall flaps of Wistar rats were transplanted to their duodenum, jejunum and colon respectively. After the operation the rats were killed at the 3rd, 6th, 9th and 12th month respectively. Intestinal metaplasia (IM) was observed in all the gastric grafts transplanted to the intestines under photomicroscope, TEM and SEM. Alkaline phosphatase positive IM was seen in the gastric graft mucosa transplanted to the duodenum and jejunum. The results showed that the formation of IM of the gastric mucosa may be related to a change of the microenvironment around the tissues and that gastric mucosa may differentiate into intestinal mucosa by the increase of pH value.


Major hepatectomy for the treatment of complex bile duct injury.
Postcholecystectomy complex bile duct injuries involving the hilar confluence, which are often associated with vascular injuries and liver atrophy, remain a considerable surgical challenge. The aim of this study is to report our experience of major hepatectomy with long-term outcome in these patients. From January 1987 to January 2002, 18 patients underwent a major hepatectomy for complex bile duct injuries. The hilar confluence was involved in all cases and was associated with vascular injuries in 13 (72%), including arterial injuries in 11, and partial liver atrophy in 15 (83%). The average time interval between the initial cholecystectomy and hepatectomy was 43 +/- 63 months and 16 (88%) patients had previously undergone an average of 2 (range 1-3) surgical repairs. Major liver resection included a right hepatectomy in 14 (78%) patients, a left hepatectomy in 3, and a left trisectionectomy in one. There was no postoperative mortality, but severe postoperative morbidity was experienced in 11 (61%) patients, including biliary fistula in 7 (39%), prolonged ascites in 8 (44%) and hemorrhage requiring reoperation in one. With a median follow-up time of 8 years (range 3 to 12), 17 (94%) patients have excellent or good results, including 13 patients without symptoms. This study shows that salvage major hepatectomy is an efficient treatment for patients with complex hilar bile duct injuries and should be considered before liver transplantation or recourse to metallic stents.


Pinopodes, leukemia inhibitory factor, integrin-β3, and mucin-1 expression in the peri-implantation endometrium of women with unexplained recurrent pregnancy loss.
To compare pinopode morphology and coverage, and expression of leukemia inhibitory factor (LIF), integrin-β3, and mucin-1 (MUC1) in the peri-implantation endometrium of women with unexplained recurrent pregnancy loss (RPL) versus normal fertile women. Exploratory clinical study. University-affiliated assisted reproductive center. Women undergoing assisted reproduction at centers of reproductive medicine in two university teaching hospitals. Endometrial biopsy samples were obtained from women with RPL (test group, n = 30) and normal fertile women (control group, n = 26) 7 days after the day of luteinizing hormone peak. Pinopode morphology and coverage were assessed by use of scanning electron microscopy. Expression of LIF, integrin β3, and MUC1 were evaluated by immunohistochemical staining. Pinopode morphology and coverage, and the expression of LIF, integrin-β3, and MUC1 in both groups. Pinopode morphology and coverage, and the expression of LIF and integrin-β3 showed no statistically significant differences between the two groups. The expression of MUC1 was statistically significantly reduced in the glandular epithelial cells and endometrial lumen of the RPL group compared with controls. The morphology and the coverage of pinopodes and expression of LIF and integrin-β3 did not change, but MUC1 expression was statistically significantly reduced in women with RPL compared with normal women.


Automated Multimodal Stimulation and Simultaneous Neuronal Recording from Multiple Small Organisms.
Fluorescent genetically encoded calcium indicators have contributed greatly to our understanding of neural dynamics from the level of individual neurons to entire brain circuits. However, neural responses may vary due to prior experience, internal states, or stochastic factors, thus generating the need for methods that can assess neural function across many individuals at once. Whereas most recording techniques examine a single animal at a time, we describe the use of wide-field microscopy to scale up neuronal recordings to dozens of Caenorhabditis elegans or other sub-millimeter-scale organisms at once. Open-source hardware and software allow great flexibility in programming fully automated experiments that control the intensity and timing of various stimulus types, including chemical, optical, mechanical, thermal, and electromagnetic stimuli. In particular, microfluidic flow devices provide precise, repeatable, and quantitative control of chemosensory stimuli with sub-second time resolution. The NeuroTracker semi-automated data analysis pipeline then extracts individual and population-wide neural responses to uncover functional changes in neural excitability and dynamics. This paper presents examples of measuring neuronal adaptation, temporal inhibition, and stimulus crosstalk. These techniques increase the precision and repeatability of stimulation, allow the exploration of population variability, and are generalizable to other dynamic fluorescent signals in small biosystems from cells and organoids to whole organisms and plants.


Postnatal ontogenetic development of neurogenic and myogenic control in the rat portal vein.
The postnatal ontogenetic development of neuro-effector control in vascular smooth muscle of the single-unit type has been studied in the rat portal vein. Contractile activity was recorded isometrically in isolated preparations from rats 2-38 days of age and in adults rats. Spontaneous activity, characteristic of the adult portal vein, appeared abruptly during the third postnatal week. Whereas, induced responses to noradernaline (NA) and acetylcholine (Ach) appeared early during the first week and responses to transmural nerve stimulation occurred at the end of the first week. The appearance of spontaneous activity was accompanied by significant increases in sensitivity to NA (log ED50) and to transmural nerve stimulation (frequency giving half maximum response), but not to Ach. Also, maximum responses for NA and nerve stimulation relative to Ach responses tended to increase during the first three weeks. It is concluded that the development of a mechanism supporting myogenic propagation as revealed by highly synchronized spontaneous contractions is an important factor for promoting the effectiveness of sympathicoadrenergic control in this type of vascular smooth muscle.


Expression and prognostic value of glutamate dehydrogenase in extrahepatic cholangiocarcinoma patients.
Glutamate dehydrogenase (GDH) produces a precursor to glutathione, an important molecule in maintaining cellular redox balance and the cancerous characteristics of tumor cells through intracellular signaling pathways. However, the underlying molecular mechanisms linking glutamate dehydrogenase and extrahepatic cholangiocarcinoma have not been elucidated yet. Herein, we examined GDH expression levels and evaluated its potential correlations with prognosis. Meanwhile, the therapeutic value of GDH targeting the Smad pathways in extrahepatic cholangiocarcinoma was explored. Immunohistochemical studies revealed that GDH expression level was correlated to CD34 expression, cellular differentiation, the presence or absence of capsular and vascular invasion, lymph node metastasis, neural invasion and patient age. Kaplan-Meier survival analysis and COX proportional hazards models demonstrated that the prognosis was closely associated with GDH expression, CD34 positivity, nerve infiltration and cell differentiation. GDH silencing significantly reduced the proliferation, migratory potential and invasive capability. We also demonstrated that GDH promoted cell proliferation and metastasis potentially through Smad-mediated induction of TGF-β signaling pathway. Therefore, GDH may be an important prognostic indicator and may provide a new target for novel treatments of extrahepatic cholangiocarcinoma.


[Systematic review on Bushen Huoxue ricipe in treating patients suffering from diminished ovarian reserve].
To systematically evaluate the efficacy and safety of Bushen Huoxue ricipe in treating patients suffering from diminished ovarian reserve. Databases such as CNKI, WanFang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched on randomized controlled trial/quasi-randomized controlled trial about Bushen Huoxue ricipe in treating patients suffering from diminished ovarian reserve form the inception of the study until June 2017. The studies were screened according to inclusion and exclusion criteria. Risk of bias evaluation tools were adopted to conduct quality evaluation. Meta-analysis on outcome indicator was performed by RevMan Version 5.3 Software. Due to the different Bushen Huoxue recipe (observation group) and the different Western medicine(control group) of all included studies, the effect size was combined by the random effect model after the subgroup analysis or sensitivity analysis was performed. Eventually 11 trials were included, including 733 cases of patients. Results of Meta-analysis indicated that, Bushen Huoxue recipe had advantages over Western medicine on lowering FSH, increasing AMH and AFC, enhancing the Chinese medicine symptom curative effect; Bushen Huoxue recipe had no advantages over Western medicine on increasing E2; the advantages of Bushen Huoxue recipe were not clear on reducing FSH/LH and increasing total effective rate because of the different outcomes to compared with the different Western medicine; no serious adverse reaction appering from Bushen Huoxue recipe was reported in the including researches. Bushen Huoxue recipe has the clinical curative effect and high safety suffering from diminished ovarian reserve. However, limited by the poor quantity of studies, these conclusions remain to be examined by more center, more sample and high-quality studies.


Oxygen mass transfer in a human tissue-engineered trachea.
On June 2008, the first human tissue-engineered trachea replacement was performed using decellularized (de-antigenised) cadaveric donor trachea, seeded with recipient epithelial cells on the internal surface of the graft and mesenchymal stem-cell-derived chondrocytes on the external. During the follow-up, cytological analysis at 4 postoperative days showed a migration of the stem-cells derived chondrocytes from the outer to the inner surface of the first 2 cm of the graft length. With the aim to rationalize these clinical findings, and under the hypothesis that cellular migration is driven by the oxygen gradients developing from the external part of the construct (exposed to O(2) deficiency) towards the better oxygenated epithelial region, an accurate computational model of oxygen transport in the trachea engineered construct was developed and solved using finite element method (FEM). Results confirm that critical limitation to oxygen transport prevalently occurs from proximal to middle section, within the first 2.8 cm of longitudinal length, in good agreement with experimental observation. In the proximal section, recognized as the most critical part of the engineered construct, the severe O(2) mass transfer limitation causes a drastic reduction of the diffusive flux within a distance of 650 microm. At cell density of 1 x 10(7)cells/cm(3), the 30% c.a of the total section area is under oxygen deficiency (O(2) partial pressure below the critical threshold of 38 mmHg). Along the whole tracheal construct, the Thiele modulus ranges within 2.3 and 3.7 in the external chondrocyte compartment, confirming thus the importance of the mass transfer limitation to oxygen diffusion rate. In general, the efficiency of the O(2) transport reduces considerably in the region close to proximal section.


Endemic hantavirus infection impairs the winter survival of its rodent host.
The influence of pathogens on host fitness is one of the key questions in infection ecology. Hantaviruses have coevolved with their hosts and are generally thought to have little or no effect on host survival or reproduction. We examined the effect of Puumala virus (PUUV) infection on the winter survival of bank voles (Myodes glareolus), the host of this virus. The data were collected by monitoring 22 islands over three consecutive winters (a total of 55 island populations) in an endemic area of central Finland. We show that PUUV infected bank voles had a significantly lower overwinter survival probability than antibody negative bank voles. Antibody negative female bank voles from low-density populations living on large islands had the highest survival. The results were similar at the population level as the spring population size and density were negatively correlated with PUUV prevalence in the autumn. Our results provide the first evidence for a significant effect of PUUV on host survival suggesting that hantaviruses, and endemic pathogens in general, deserve even more attention in studies of host population dynamics.


Low-Dose Radiation Therapy for Benign Painful Skeletal Disorders: The Typical Treatment for the Elderly Patient?
To prospectively evaluate the short-term and long-term efficacy of low-dose radiation therapy (RT) for calcaneodynia, achillodynia, painful gonarthrosis, and painful bursitis trochanterica in elderly patients aged ≥70 years. Between October 2011 and October 2013, patients aged ≥70 years with painful degenerative disorders of joints were recruited for a prospective trial. Single doses of 0.5 to 1.0 Gy and a total dose of 6.0 Gy per series were used. Pain was measured before and right after RT (early response) with a 10-point visual analogue scale. Additionally, pain relief was measured with the 4-point pain scale according to "von Pannewitz" immediately on completion of RT and during follow-up. We defined a good response as complete pain relief and markedly improved. A total of 166 evaluable patients with a mean age of 76.6 years (range, 70-90 years) with calcaneodynia (n=51), achillodynia (n=8), painful gonarthrosis (n=80), and painful bursitis trochanterica (n=27) were recruited. The mean visual analogue scale value before treatment was 6.38 and immediately upon completion of RT was 4.49 (P<.001). Concerning the von Pannewitz status immediately on completion of RT, 6 patients were free of pain, 56 were much improved, 47 reported slight improvement, and 57 experienced no change. After a median follow-up of 29 months, 109 patients could be reached for evaluation of follow-up results. Thirty-three patients were free of pain, 21 had marked improvement, 18 had some improvement, and 37 experienced no change. Therefore, a good response immediately on completion of RT could be achieved in 62 of 166 patients, and with the follow-up in 54 of 109 patients (P=.001). Low-dose RT is a very effective treatment for the management of painful degenerative disorders of joints in the elderly. Low-dose RT offers a low-risk, genuinely conservative, noninvasive therapeutic alternative for elderly patients.


Epigenetics and plant evolution.
A fundamental precept of evolutionary biology is that natural selection acts on phenotypes determined by DNA sequence variation within natural populations. Recent advances in our understanding of gene regulation, however, have elucidated a spectrum of epigenetic molecular phenomena capable of altering the temporal, spatial, and abundance patterns of gene expression. These modifications may have morphological, physiological, and ecological consequences, and are heritable across generations, suggesting they are important in evolution. A corollary is that genetic variation per se is not always a prerequisite to evolutionary change. Here, we provide an introduction to epigenetic mechanisms in plants, and highlight some of the empirical studies illustrative of the possible connections between evolution and epigenetically mediated alterations in gene expression and morphology.


Near-Infrared Light Controllable DNA Walker Driven by Endogenous Adenosine Triphosphate for in Situ Spatiotemporal Imaging of Intracellular MicroRNA.
As a powerful signal amplification tool, the DNA walker has been widely applied to detect rare microRNA (miRNA) in vivo. Despite the significant advances, a near-infrared (NIR) light controllable DNA walker for signal amplification powered by an endogenous initiator has not been realized, which is crucial for spatiotemporal imaging of miRNA in living cells with high sensitivity. Herein, we constructed a NIR-photoactivatable DNA walker system, which was powered by endogenous adenosine triphosphate (ATP) for in situ miRNA imaging with spatial and temporal resolution. The system was very stable with an extremely low fluorescent background for the bioimaging in living cells. We employed upconversion nanoparticles (UCNPs) as the carriers of the DNA probe and transducers of converting NIR to UV light. Coupled with the DNA walker fueled by intracellular ATP, a smart system based on the NIR light initiated DNA walker was successfully developed for precise spatiotemporal control in living cells. Triggered by NIR light, the DNA walker could autonomously and progressively travel along the track with the assistance of intracellular ATP. The system has been successfully applied for in situ miRNA imaging in different cell lines with highly spatial and temporal resolution. This strategy can expand NIR photocontrol the DNA walker for precise imaging in a biological system.


Discrepancy between information provided and information required by emergency physicians for long-term care patients.
The primary objective of this study was to identify information included in long-term care (LTC) transfer documentation and to compare it to the information required by local emergency department (ED) physicians to provide optimal care and make decisions for LTC patients. A retrospective chart review was conducted for a sample of LTC residents transferred by ambulance to the ED of an academic, tertiary care hospital over a 1-year period. All emergency physicians working at the institution were invited to complete an online questionnaire about information included in LTC transfer documentation and information required by emergency physicians to provide care for LTC patients. Of the 200 charts reviewed, the most common information transferred to the ED with the LTC patient was the patient's past medical history (n=184, 92.0%), name of family physician (n=182, 91.0%), a list of known allergies (n=179, 89.5%), the reason for transfer to the ED (n=155, 77.5%), the patient's emergency contact information (n=152, 76.0%), and medication administration record (n=150, 75.0%). From a physician's perspective, the most frequently requested pieces of information included reason for transfer, past medical history, cognitive status, advanced directives for level of care and resuscitation, and the patient's emergency contact information. This information was provided 77.5% (n=155), 92.0% (n=184), 24.0% (n=48), 62.0% (n=124), and 76.0% (n=152) of the time, respectively. Our study demonstrates a clear discrepancy between information provided and information required by emergency physicians for LTC patients. Quality improvement initiatives at the local level may help reduce this discrepancy.


Management of parapharyngeal space tumors.
In this study, we aimed to investigate the influence of the surgical approaches for the parapharyngeal space tumors. Eighteen patients with parapharyngeal space tumors diagnosed and treated at our clinic between 1992 and 2001 were included in this study. Surgical techniques used included transcervical, transparotid, transcervical-transmandibular, and infratemporal-A approaches depending on tumor size, location, vascularity, and malignant potential. Postoperative radiation therapy was applied in all malignant tumor. Postoperative morbidity, complications, and recurrence were evaluated. We found that 55.6 % of the PPS tumor were of salivary gland origin, 27.8 % were neurogenic, and 16.6% were miscellaneous. Of the four surgical techniques, transcervical approach were used most commonly. Postoperative morbidities were at acceptable levels. Our surgical survival rates were 100% for benign and 40% for malignant PPS tumors after a mean follow-up of 54 months.


[Treatment of dyslipidemia of the elderly with simvastatin and pravastatin. Effectiveness and tolerance].
After reviewing the literature concerning the advisability and efficacy of dyslipidemia treatment in old age, the authors present their experience with the use of HMG CoA reductase inhibitors. Twenty-five patients were treated with simvastatin and 20 with pravastatin. Already after one month of therapy, both drugs had induced a reduction of total cholesterol, LDL-cholesterol, and triglycerides, as well as an increase of HDL-cholesterol. These changes were found to be even more marked after three months of treatment. Altogether, tolerability of both drugs was good. However, recurrent episodes of nose bleeding were observed in two patients with normal blood clotting activity.


Influence of a mutation in IFN-γ receptor 2 (IFNGR2) in human cells on the generation of Th17 cells in memory T cells.
The T cell subsets involved in inflammatory reactions are mainly the IFN-γ secreting Th1 cells and IL17-producing Th17 cells. Although Th17 cells are primed in the thymus, there is evidence that Th17 cells can be generated from effector memory CD4(+) T cells. Cytokines as IL-6, TGF-β, IL-21 and IL-23 involved in development of Th17 cells are well described. Here we analyzed the impact of a mutation in the IFN-γ receptor 2 (IFN-γR2) on the induction of Th17 cells. By isolation of T cells and monocytes of a patient with this mutation we could demonstrate an inhibitory role of IFN-γ signaling as IFN-γR2-deficient monocytes induce a higher percentage of IL-17(+) cells from both healthy and IFN-γR2-deficient CD4(+) T cells. This data confirm the interference of these two T helper subsets and points to a balance of Th1 and Th17 cells obtained by their own cytokine production and their interplay with APCs.


Synthesis and biological activity of nifuroxazide and analogs.
Nifuroxazide and thirteen analogs were synthesized from substituted benzoic acids and minimal inhibitory concentrations were determined using the serial dilution tests, in three sequential steps. Nifuroxazide and chloramphenicol were used as reference standards. The tests were performed in TSB against the standard bacterial strain of Staphylococcus aureus ATCC 25923.