Calcium/calmodulin signaling controls osteoblast growth and differentiation.
Ca2+ is a ubiquitous intracellular messenger responsible for controlling numerous cellular processes including fertilization, mitosis, neuronal transmission, contraction and relaxation of muscles, gene transcription, and cell death. At rest, the cytoplasmic Ca2+ concentration [Ca2+]i is approximately 100 nM, but this level rises to 500-1,000 nM upon activation. In osteoblasts, the elevation of [Ca2+]i is a result of an increase in the release of Ca2+ from endoplasmic reticulum and/or extracellular Ca2+ influx through voltage gated Ca2+ channels. Many of the cellular effects of Ca2+ are mediated by the Ca2+ binding protein, calmodulin (CaM). Upon binding up to four calcium ions, CaM undergoes a conformational change, which enables it to bind to specific proteins eliciting a specific response. Calmodulin kinase II (CaMKII) is a major target of the Ca(2+)/CaM second messenger system. Once bound to Ca(2+)/CaM, the multimeric CaMKII is released from its autoinhibitory status and maximally activated, which then leads to an intraholoenzyme autophosphorylation reaction. Calcineurin (Cn) is another major target protein that is activated by Ca(2+)/CaM. Cn is a serine-threonine phosphatase that consists of a heterodimeric protein complex composed of a catalytic subunit (CnA) and a regulatory subunit (CnB). Upon activation, Cn directly binds to, and dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors within the cytoplasm allowing them to translocate to the nucleus and participate in the regulation of gene expression. This review will examine the potential mechanisms by which calcium, CaM, CaMKII, and Cn/NFAT control osteoblast proliferation and differentiation.


Muscular nociceptors.
The discharge characteristics of various types of muscle afferents in response to mechanical and chemical painful stimulation were studied in cats anaesthetized with chloralose. In a few experiments, heat was used as an additional stimulus. The results indicate that only among the fibre groups III and IV, units are regularly found that have high thresholds on mechanical and thermal stimulation, and that response to administration of algesic agents in pain-producing doses. The response behaviour of individual group III and group IV afferent units to the various stimuli was very similar, but when the fibre populations are compared, the group III afferents appeared to be more sensitive to the mechanical and chemical stimuli of this study. It is concluded that both the fibre groups III and IV include afferent units possessing receptive properties enabling them to serve as muscular nociceptors.


Data Representativeness in Accessibility Datasets: A Meta-Analysis.
As data-driven systems are increasingly deployed at scale, ethical concerns have arisen around unfair and discriminatory outcomes for historically marginalized groups that are underrepresented in training data. In response, work around AI fairness and inclusion has called for datasets that are representative of various demographic groups. In this paper, we contribute an analysis of the representativeness of age, gender, and race & ethnicity in accessibility datasets-datasets sourced from people with disabilities and older adults-that can potentially play an important role in mitigating bias for inclusive AI-infused applications. We examine the current state of representation within datasets sourced by people with disabilities by reviewing publicly-available information of 190 datasets, we call these accessibility datasets. We find that accessibility datasets represent diverse ages, but have gender and race representation gaps. Additionally, we investigate how the sensitive and complex nature of demographic variables makes classification difficult and inconsistent (e.g., gender, race & ethnicity), with the source of labeling often unknown. By reflecting on the current challenges and opportunities for representation of disabled data contributors, we hope our effort expands the space of possibility for greater inclusion of marginalized communities in AI-infused systems.


An Implementation Study of Relationship Checkups as Home Visitations for Low-Income At-Risk Couples.
Couples with the greatest need for relationship health maintenance and intervention are often least able to afford and access it; therefore, accessible, affordable, effective, and brief interventions are needed to improve relationship health for those who need it most. Consequently, this paper examined whether a brief relationship intervention could be effectively implemented with a low-income, underserved population. All enrolled participants (N = 1,312) received the Relationship Checkup, which consists of an assessment and a feedback session delivered in their homes or at a local clinic at their request. Measures assessed relationship satisfaction, communication, psychological and physical aggression, and intimacy at baseline and 1-month follow-up, and program and relationship satisfaction at 6-month follow-up. All participants reported significant improvements on all outcomes with small effect sizes. However, moderation analyses suggested that distressed couples reported significantly larger effects across the board. Overall, participants reported that they were highly satisfied with the intervention both immediately after its delivery and 6 months later. Findings provide preliminary support for the effectiveness of this brief checkup and point to the utility of offering these kinds of low-cost brief interventions in flexible formats for those who might have the most difficulty accessing them.


Reading comprehension and its relation to the quality of functional hearing: evidence from readers with different functional hearing abilities.
Three groups of students--19 hard of hearing, 20 deaf, and a control group of 36 typically developing hearing readers--were compared on their ability to process written words at the lexical level and on their comprehension of words within the structure of a sentence. Findings generally suggested that severe prelingual hearing loss does not prevent the development of word processing strategies adequate for efficient processing of written words at the lexical level, although such hearing loss seems to put individuals at risk of failure in internalizing syntactic knowledge crucial for proper processing of words at the sentence level. Evidence further indicated that neither the amount of functional hearing (deaf vs. hard of hearing), the hearing status of their parents (hearing impaired vs. hearing), nor the use of sign language as a primary communication mode was a direct cause in this regard.


Next-generation sequencing in clinical oncology: next steps towards clinical validation.
Compelling evidence supports the transition of next generation sequencing (NGS) technology from a research environment into clinical practice. Before NGS technologies are fully adopted in the clinic, they should be thoroughly scrutinised for their potential as powerful diagnostic and prognostic tools. The importance placed on generating accurate NGS data, and consequently appropriate clinical interpretation, has stimulated much international discussion regarding the creation and implementation of strict guidelines and regulations for NGS clinical use. In the context of clinical oncology, NGS technologies are currently transitioning from a clinical research background into a setting where they will contribute significantly to individual patient cancer management. This paper explores the steps that have been taken, and those still required, for the transition of NGS into the clinical area, with particular emphasis placed on validation in the setting of clinical oncology.


Hypertension from Framingham to ALLHAT: translating clinical trials into practice.
Despite decades of observational and clinical data about the effectiveness of treating hypertension, most Americans are still not being adequately treated. It makes little sense that much of our efforts are directed toward performing large trials to find out whether newer, more expensive agents are superior to conventional therapy, especially when little evidence shows any benefit to the newer drugs. Rather, our priority should be to treat more patients and to treat them more aggressively.


Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid cancer (DTC) in juvenile versus adult patients.
In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.


Association between traffic-related air pollution and osteoporotic fracture hospitalizations in inland and coastal areas: evidences from the central areas of two cities in Shandong Province, China.
Our result showed that short-term exposure to traffic-related air pollutants (TRAPs) might increase the risk of hospitalizations for osteoporotic fractures. It was suggested that government should formulate emission reduction policies to protect the health of citizens. As the main source of urban air pollution in China, exhaust emissions of motor vehicles have been linked to adverse health outcomes, but evidence of the relationship between short-term exposure to TRAPs and osteoporotic fractures is still relatively rare. In this study, a total of 5044 inpatients from an inland city (Jinan) and a coastal city (Qingdao), two cities with developed transportation in Shandong Province, were included. A generalized additive model (GAM) was used to investigate the association between TRAPs and hospitalizations for osteoporotic fractures. The stratified analyses were performed by gender and age. Positive associations between TRAPs and osteoporotic fracture hospitalizations were observed. We found that short-term exposure to TRAPs was associated with increased numbers of hospitalizations for osteoporotic fractures. PM2.5 and PM10 were statistically significant associated with hospitalizations for osteoporotic fractures at both single-day and multiday lag structures only in Qingdao, with the strongest associations at lag06 and lag07 [RR=1.0446(95%CI: 1.0018,1.0891) for PM2.5, RR=1.0328(95%CI: 1.0084,1.0578) for PM10]. For NO2 and CO, we found significant associations at lag4 in the single lag structure in Jinan [RR=1.0354 (95%CI: 1.0071, 1.0646) for NO2, RR=1.0014 (95%CI: 1.0002, 1.0025) for CO], while only CO at lag4 was significantly associated with hospitalizations for osteoporotic fractures in Qingdao [1.0038 (1.0012, 1.0063)]. Stratified analyses indicated that the associations were stronger in females and older individuals (65 + years). This study implied that short-term exposure to TRAPs pollution was associated with an increased risk of hospitalizations for osteoporotic fractures. Female patients and patients aged 65 + years appeared to be more vulnerable to TRAPs, suggesting that poor air quality is a modifiable risk factor for osteoporotic fractures.


[The epidermis as an immune organ].
The epidermis possesses everything required for initiation of an immune response. It harbors antigen-presenting Langerhans cells, it produces immune modulatory cytokines, and (so far shown only in the murine system) it contains a distinct T cell population. Both upregulating and downregulating signals, leading to either sensitization or tolerance, are generated in the epidermis after exposure to antigens, and both have distinct cellular origins. While sensitizing and tolerogenic signals are usually balanced in such a way that Langerhans cell-generated sensitization is predominant, a breakdown of Langerhans cell function results in suppressive mechanisms. The structural and antigenic similarity between epidermis and thymus, the secretion of cytokines by keratinocytes, the migration of lymphocytes into the epidermis and the heterogeneity of TCR expression on Thy-1+ dendritic epidermal cells residing in (murine) epidermis and cell lines derived thereof all suggest that the epidermis is a site of postthymic or extrathymic T cell maturation.


The epitope and neutralization mechanism of AVFluIgG01, a broad-reactive human monoclonal antibody against H5N1 influenza virus.
The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus.


Distinguishing specific and nonspecific interdomain interactions in multidomain proteins.
Multidomain proteins account for over two-thirds of the eukaryotic genome. Although there have been extensive studies into the biophysical properties of isolated domains, few have investigated how the domains interact. Spectrin is a well-characterized multidomain protein with domains linked in tandem array by contiguous helices. Several of these domains have been shown to be stabilized by their neighbors. Until now, this stabilization has been attributed to specific interactions between the natural neighbors, however we have recently observed that nonnatural neighboring domains can also induce a significant amount of stabilization. Here we investigate this nonnative stabilizing effect. We created spectrin-titin domain pairs of both spectrin R16 and R17 with a single titin I27 domain at either the N- or the C-terminus and found that spectrin domains are significantly stabilized, through slowed unfolding, by nonnative interactions at the C-terminus only. Of particular importance, we show that specific interactions between natural folded neighbors at either terminus confer even greater stability by additionally increasing the folding rate constants. We demonstrate that it is possible to distinguish between natural stabilizing interactions and nonspecific stabilizing effects through examination of the kinetics of well chosen mutant proteins. This work adds to the complexity of studying multidomain proteins.


The current status of thromboprophylaxis after trauma: a story of confusion and uncertainty.
It is difficult to support a standard of care for venous thromboprophylaxis after trauma when there is no convincing research that any of the currently used methods is consistently effective. Because many conclusions from the nontrauma literature have been misleadingly extrapolated to trauma patients, this review focuses exclusively on trauma articles. These articles present variable results. The rates of deep venous thrombosis and pulmonary embolism are widely different even among similar trauma populations. The heparin-unfractionated or low-molecular-weight and calf compression methods fail to show a reproducible effect in decreasing venous thromboembolic events. The current methods of venous thromboprophylaxis after trauma are inadequate and further research in this area is direly needed.


Comparison of Different Analgesia Drug Regimens for Pain Control During Extracorporeal Shock Wave Lithotripsy for Renal Stones: A Randomized Control Study.
With the increased use of extracorporeal shock wave lithotripsy (ESWL), the management of urolithiasis has become much convenient for the patients and the health care professionals alike. However, associated with the procedure is the common complaint of pain. No agreed upon pain management strategy has yet been developed for the procedure. We compared the effect of different analgesia drug regiments for pain control. A randomised controlled trial was carried out in Shifa International Hospital from between July 2015 to January 2016. A total of 135 patients were divided into three groups; group A received 30 g lidocaine 2% gel applied locally on corresponding lumber area 30 minutes before the procedure, group B received oral naproxen sodium 550 mg 45 minutes before the procedure, and group C received both oral naproxen and lidocaine gel. Patients were supplemented with intravenous nalbuphine during the procedure. The pain was assessed with 0-10 visual analogue scale. Both pre-procedure and post-procedure pain score was measured. Among 135 patients, 105 (77.8%) were male and 29 (21.5%) were female with mean age of 38.7 ± 1.31 years. There was no difference of mean pain score or need for supplemental intravenous nalbuphine between groups B and C but there was significantly decreased mean pain score and need for supplemental intravenous nalbuphine in groups B and C in comparison with group A. The use of oral naproxen sodium with or without the addition of lidocaine gel during ESWL is a promising option for pain management during the procedure with significant improvement in comparison with lidocaine gel alone.


Phosphoinositide 3-kinase/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.
In this study, it was found that undifferentiated myoblasts were more vulnerable to menadione-induced oxidative stress than differentiated myotubes. Cell death occurred with a relatively low concentration of menadione in myoblasts compared to myotubes. With the same concentration of menadione, the Bcl-2/Bax ratio decreased and nuclei containing condensed chromatin were observed in myoblasts to a greater extent than in myotubes. However, myotubes became increasingly susceptible to menadione when phosphoinositide 3-kinase (PI3-K) was blocked by pre-incubation with LY294002, a PI3-K inhibitor. Actually, PI3-K activity was reduced by menadione in myoblasts but not in myotubes. In addition, the phosphorylation of Akt, a downstream effector of PI3-K, was inhibited in myoblasts by menadione but increased in myotubes. Both LY294002 and API-2, an Akt inhibitor, decreased the Bcl-2/Bax ratio in menadione-exposed myotubes. These results suggest that the differential activity of PI3-K/Akt signalling is responsible for the differential susceptibility of myoblasts and myotubes to menadione-induced oxidative stress.


Overview of 3-year experience with large-scale electronic portal imaging device-based 3-dimensional transit dosimetry.
To assess the usefulness of electronic portal imaging device (EPID)-based 3-dimensional (3D) transit dosimetry in a radiation therapy department by analyzing a large set of dose verification results. In our institution, routine in vivo dose verification of all treatments is performed by means of 3D transit dosimetry using amorphous silicon EPIDs. The total 3D dose distribution is reconstructed using a back-projection algorithm and compared with the planned dose distribution using 3D gamma evaluation. Dose reconstruction and gamma evaluation software runs automatically in our clinic, and analysis results are (almost) immediately available. If a deviation exceeds our alert criteria, manual inspection is required. If necessary, additional phantom measurements are performed to separate patient-related errors from planning or delivery errors. Three-dimensional transit dosimetry results were analyzed per treatment site between 2012 and 2014 and the origin of the deviations was assessed. In total, 4689 of 15,076 plans (31%) exceeded the alert criteria between 2012 and 2014. These alerts were patient-related and attributable to limitations of our back-projection and dose calculation algorithm or to external sources. Clinically relevant deviations were detected for approximately 1 of 430 patient treatments. Most of these errors were because of anatomical changes or deviations from the routine clinical procedure and would not have been detected by pretreatment verification. Although cone beam computed tomography scans yielded information about anatomical changes, their effect on the dose delivery was assessed quantitatively by means of 3D in vivo dosimetry. EPID-based transit dosimetry is a fast and efficient dose verification technique. It provides more useful information and is less time-consuming than pretreatment verification measurements of intensity modulated radiation therapy and volumetric modulated arc therapy. Large-scale implementation of 3D transit dosimetry is therefore a powerful method to guarantee safe dose delivery during radiation therapy.


Lymphocyte subsets in jejunal and ileal Peyer's patches of normal and gnotobiotic minipigs.
The size and location of Peyer's patches (PP) in the jejunum and ileum and their composition of lymphocyte subsets (B, CD2+, CD4+, CD8+) have been studied in conventional and gnotobiotic Göttingen minipigs. Each PP in the small intestine remained at the same site and was of comparable length between 2 and 12 months of age. In 1.5-month-old conventional minipigs the histology of the compartments differed between the continuous PP in the terminal ileum (ilPP) and the discrete PP in the jejunum (jejPP). No such difference was seen in gnotobiotic or in 12-month-old animals. The composition of lymphocyte subsets showed striking differences with significantly more B and less T, CD4+ and CD8+ cells in ilPP in 1.5-month-old minipigs in comparison with 12-month-olds. Mesenteric lymph nodes and jejPP displayed a typical pattern of lymphocyte subsets. The size of the lymphocyte compartments in PP and their cellular composition depends largely on age and microbial influences from the gut lumen, which might be of major importance for studies on the function of the gut-associated immune system in the pig.


Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage.
Keloids are a dermal fibrotic disease whose etiology remains totally unknown and for which there is no successful treatment. Here, we employed cDNA microarray analysis to examine gene expression in keloid lesions and control skin. We found that 32 genes among the 9000 tested were strongly up-regulated in keloid lesions, of which 21 were confirmed by Northern blotting. These included at least seven chondrocyte/osteoblast marker genes, and RT-PCR analysis revealed that transcription factors specific for these genes, SOX9 and CBFA1, were induced. Immunostaining and in situ hybridization further supported that these markers are expressed in keloid lesions. Intriguingly, scleraxis, a transcription factor known as a marker of tendons and ligaments, was also induced in keloid fibroblasts. We propose that reprogramming of gene expression or disordered differentiation from a dermal pattern to that of a chondrocytic/osteogenic lineage, probably closer to that of tendon/ligament lineage, may be involved in the etiology of keloids.


Screening of curcumin-derived isoxazole, pyrazoles, and pyrimidines for their anti-inflammatory, antinociceptive, and cyclooxygenase-2 inhibition.
Curcumin has shown pharmacological properties against different phenotypes of various disease models. Different synthetic routes have been employed to develop its numerous derivatives for diverse and improved therapeutic roles. In this study, we have synthesized curcumin derivatives containing isoxazole, pyrazoles, and pyrimidines and then the synthesized molecules were evaluated for their anti-inflammatory and antinociceptive activities in experimental animal models. Acute toxicity of synthesized molecules was evaluated in albino mice by oral administration. Any behavioral and neurological changes were observed at dose of 10 mg/kg body weight. Additionally, cyclooxygenase-2 (COX-2) enzyme inhibition studies were performed through in vitro assays. In vivo anti-inflammatory studies showed that curcumin with pyrimidines was the most potent anti-inflammatory agent which inhibited induced edema from 74.7% to 75.9%. Compounds 7, 9, and 12 exhibited relatively higher prevention of writhing episodes than any other compound with antinociceptive activity of 73.2%, 74.9%, and 71.8%, respectively. This was better than diclofenac sodium (reference drug, 67.1% inhibition). Similarly, COX-2 in vitro inhibition assays results revealed that compound 12 (75.3% inhibition) was the most potent compound. Molecular docking studies of 10, 11, and 12 compounds in human COX-2 binding site revealed the similar binding modes as that of other COX-2-selective inhibitors.


ASCA (Anti-Saccharomyces cerevisiae Antibody) in Patients With Scleroderma.
The majority of scleroderma (SSc) patients present gastrointestinal involvement. Motility is usually compromised but few studies address permeability changes in the intestinal wall. ASCA (anti-Saccharomyces cerevisiae antibodies) positivity is associated with increased intestinal permeability. In this study we aimed to investigate ASCA positivity in SSc patients and its association with clinical, serological and epidemiological data. Seventy-four SSc patients and 57 healthy controls were studied for ASCA (IgG and IgA) positivity by ELISA. ASCA positivity was associated with demographic, clinical severity index (by Medsger score) and serological data in SSc patients. ASCA-IgG was positive in 32/74 (43.2%) patients of the SSc group and 1/57 (1.7%) of controls (p < 0.0001); ASCA-IgA was positive in 12/74 (16.2%) of the SSc group and 3/57 (5.2%) of controls (p = 0.05). In univariate analysis, ASCA-IgG presence was associated positively with African ethnic background (p < 0.001) and negatively associated with anticentromere antibodies (p = 0.013); ASCA-IgA had a negative association with Medsger score (p = 0.05). In multivariate analysis ASCA-IgG associated independently only with African ethnic background. Positivity for ASCA-IgG and ASCA-IgA is higher among scleroderma patients than controls. African descendants have more positivity for ASCA-IgG. ASCA-IgA is less frequent in patients with a more severe disease.


Combination of Iron and Zinc Enhanced the Root Cell Division, Mitotic Regularity and Nucleolar Activity of Hexaploid Triticale.
Hexaploid triticale results from crosses between durum wheat and rye. Despite its high agronomic potential, triticale is mainly used for livestock feed. Triticale surpasses their parental species in adaptability and tolerance to abiotic and biotic stresses, being able to grow in acidic soils where a high amount of iron (Fe) and zinc (Zn) is typical. On the other hand, high amounts of these essential trace elements can be cytotoxic to bread wheat. The cytotoxicity induced by seed priming with a high concentration of Fe and Zn impaired root cell division and induced nucleolar changes in bread wheat. Such cytogenetic approaches were expedited and successfully determined cytotoxic and suited micronutrient dosages for wheat nutripriming. With this study, we intended to analyse the hexaploid triticale cv 'Douro' root mitotic cell cycle and nucleolar activity after seed priming performed with aqueous solutions of iron (Fe) and/or zinc (Zn), containing a concentration that was previously considered cytotoxic, to bread wheat and to infer the higher tolerance of triticale to these treatments. The overall cytogenetic data allowed us to conclude that the Fe + Zn treatment enhanced the root mitotic index (MI), mitosis regularity and nucleolar activity of 'Douro' relative to the control and the individual treatments performed with Fe or Zn alone. The Fe + Zn treatment might suit triticale biofortification through seed priming.


Qualitative X-ray spectrometric study to demonstrate ruthenium in central nervous system structures, after intraperitoneal injection of ruthenium red to adult rats.
A qualitative X-ray spectrometric study oriented to demonstrate ruthenium (Ru) in central nervous system was made after intraperitoneal (i.p.) injection of ruthenium red (RuR) to adult rats. Ru signals were depicted in the brain synaptosomal fraction since 60 min after RuR i.p. administration, corresponding to the latency period of the convulsive model injecting RuR systemically to adult rats. Ru signals were initially detected in pineal gland and periventricular regions, whereas X-rays from Ru atoms in cerebral cortex were detected at longer time intervals after RuR i.p. injection. It is concluded that RuR, a non-liposoluble substance, when injected systemically, passes from the blood stream to brain parenchyma, probably through areas without blood-brain barrier, reaching the neural elements related to the mechanisms of production of convulsions.


Comprehensive comparison of carotid endarterectomy primary closure and patch angioplasty: A single-institution experience.
Carotid endarterectomy (CEA) is an effective intervention for the treatment of high-grade carotid stenosis. Technical preferences exist in the operative steps including the use patch for arteriotomy closure. The goals of this study are to compare the rate of postoperative complications and the rate of recurrent stenosis between patients undergoing primary versus patch closure during CEA. Retrospective chart review was conducted for patients who underwent CEA at single institution. Vascular surgeons mainly performed patch closure technique while neurosurgeons used primary closure. Patients' baseline characteristics as well as intraprocedural data, periprocedural complications, and postprocedural follow-up outcomes were captured. Seven hundred and thirteen charts were included for review with mean age of 70.5 years (SD = 10.4) and males representing 64.2% of the cohort. About 49% of patients underwent primary closure while 364 (51%) patients underwent patch closure. Severe stenosis was more prevalent in patients receiving patch closure (94.5% vs. 89.4%; P = 0.013). The incidence of overall complications did not differ between the two procedures (odds ratio = 1.23, 95% confidence intervals = 0.82-1.85; P = 0.353) with the most common complications being neck hematoma, strokes, and TIA. Doppler ultrasound imaging at 6 months postoperative follow-up showed evidence of recurrent stenosis in 15.7% of the primary closure patients compared to 16% in patch closure cohort. Both primary closure and patch closure techniques seem to have similar risk profiles and are equally robust techniques to utilize for CEA procedures.


Biocompatibility evaluation of sputtered zirconium-based thin film metallic glass-coated steels.
Thin film metallic glasses comprised of Zr48Cu36Al8Ag8 (at.%) of approximately 1.5 μm and 3 μm in thickness were prepared using magnetron sputtering onto medical grade 316L stainless steel. Their structural and mechanical properties, in vitro corrosion, and antimicrobial activity were analyzed. The amorphous thin film metallic glasses consisted of a single glassy phase, with an absence of any detectable peaks corresponding to crystalline phases. Elemental composition close to the target alloy was noted from EDAX analysis of the thin film. The surface morphology of the film showed a smooth surface on scanning electron microscopy and atomic force microscopy. In vitro electrochemical corrosion studies indicated that the zirconium-based metallic glass could withstand body fluid, showing superior resistance to corrosion and electrochemical stability. Interactions between the coated surface and bacteria were investigated by agar diffusion, solution suspension, and wet interfacial contact methods. The results indicated a clear zone of inhibition against the growth of microorganisms such as Escherichia coli and Staphylococcus aureus, confirming the antimicrobial activity of the thin film metallic glasses. Cytotoxicity studies using L929 fibroblast cells showed these coatings to be noncytotoxic in nature.


Safety of vertebral augmentation with cranio-caudal expansion implants in vertebral compression fractures with posterior wall protrusion.
Vertebral augmentation (VA) has become routinely used in vertebral compression fractures (VCFs). VCFs are often associated with posterior wall protrusions (PWPs), which theoretically contraindicates vertebroplasty due to a higher risk of neurological complications. The latest generation of VA devices uses intravertebral cranio-caudal expandable implants to improve the correction of structural deformities but could also be used to prevent further PWP during cement injection. The aim of this study was to evaluate the safety of VA with expandable implant for VCFs with PWP. All consecutive patients treated with expandable implants were considered eligible for inclusion if they met the following criteria: (1) non-neurological VCF, (2) considered unstable (A3-A4 in AOSpine classification), (3) significant PWP (> 2 mm), (4) back pain with a visual analogue scale (VAS) ≥ 4. PWPs were independently measured by two investigators; Pearson's statistics were used for interobserver reproducibility. Fifty-one consecutive patients, with a mean age of 75 ± 8.3 years (range, 50-92), were included. There was a slight decrease between mean preoperative (6.7 mm ± 2.2 mm) and postoperative (6.5 mm ± 2.2 mm) PWP (p = 0.02), with an excellent interobserver reproducibility (Pearson correlation coefficient = 0.92). A mean kyphosis reduction of 34.9% (± 28.4) was observed (p < 0.001). Forty-two patients (82.4%) had significant pain improvements (mean preoperative VAS = 6.9 [± 1.7] versus 3.1 [± 2.0] postoperatively [p < 0.001]). Secondary adjacent level fractures were noted in 16 patients (31.4%), with a reduction of that risk down to 18.8% if a preventive adjacent vertebroplasty was performed, without reaching the significance threshold (p = 0.14). VA with expandable implants appeared safe for non-neurological VCFs with PWP, while allowing satisfactory pain relief. • Vertebral augmentation with cranio-caudal expandable implants is safe for non-neurological vertebral compression fractures with posterior wall protrusions. • Vertebral augmentation with cranio-caudal expandable implants might increase the occurrence of secondary adjacent level fractures. • Adjacent level vertebroplasty might be helpful to prevent secondary adjacent level fractures.


[Stress analysis of the staggered and straight placement of implants in the mandibular posterior region under the localized load].
To compare the stress distribution of the staggered and straight placement of implants in the mandibular posterior region. Using three-dimensional finite element approach to analyze the stress distribution and variance regularity under the localized load. Under vertical load, the stress peak value reduced when wide implant was placed straight (min: 3.70 MPa), but slightly increased when normal implant was placed staggered (max: 8.32 MPa); under the inclined load from buccal to lingual direction, the stress peak value reduced when the wide implant was placed in straight line (min: 12.29 MPa) or normal implant was placed staggered with buccal offset configuration (min: 15.48 MPa), but increased with lingual offset configuration (max: 23.60 MPa). Wide implant (> or = 4 mm) with straight placement should be adopted to reduce the stress peak value and improve stress distribution, when the buccolingual diameter of the alveolar ridge in the mandibular posterior region was wide.


Sexual orientations in perspective.
This article presents a new paradigm for understanding the complexity of human sexual, affectional, and erotic attractions--commonly known as sexual orientation. This new paradigm recognizes that there is great diversity among sexual orientations, erotic and emotional attractions, behaviors, and identities and that there are complex interrelations among these dimensions. Sexual orientation is determined by multiple influences, including a wide range of sociocultural factors. The development of sexual orientation is arrived at through multiple pathways. Individuals with the same sexual orientation may have little else in common. Thus, a model of sexual orientation is presented that is based on multiplicity, not sameness, and that examines the overlapping identities and statuses of culture, gender, age, race, ethnicity, class, disability, and sexuality.


pKNOT v.2: the protein KNOT web server.
Knotted proteins have recently received lots of attention due to their interesting topological novelty as well as its puzzling folding mechanisms. We previously published a pKNOT server, which provides a structural database of knotted proteins, analysis tools for detecting and analyzing knotted regions from structures as well as a Java-based 3D graphics viewer for visualizing knotted structures. However, there lacks a convenient platform performing similar tasks directly from 'protein sequences'. In the current version of the web server, referred to as pKNOT v.2, we implement a homology modeling tool such that the server can now accept protein sequences in addition to 3D structures or Protein Data Bank (PDB) IDs and return knot analysis. In addition, we have updated the database of knotted proteins from the current PDB with a combination of automatic and manual procedure. We believe that the updated pKNOT server with its extended functionalities will provide better service to biologists interested in the research of knotted proteins. The pKNOT v.2 is available from http://pknot.life.nctu.edu.tw/.


Effects of glutamine on intestinal mucus barrier after burn injury.
Severe burns may cause intense stress and persistent inflammation, resulting in intestinal mucosal barrier damage. In this study, we evaluated the effects of glutamine (Gln) on intestinal mucus barrier after burn injury. The results showed that glutamine could improve intestinal mucosal blood flow (IMBF), decrease diamine oxidase (DAO) activity, and reduce intestine damage, thereby alleviate intestinal mucous permeability. Severe burn was associated with subsequent decrease in mucus thickness, levels of hexose, sialic acid, and protein. Glutamine administration might partially reverse these changes. Additional experiments showed that supplementation with glutamine could markedly raise the content of glutamine, glutathione (GSH), and ATP in intestinal tissue. Moreover, the levels of mRNA and protein expression of MUC2, intestinal trefoil factor (ITF) were increased remarkably, but contrary to the trend of GRP-78, CHOP. These results suggest that glutamine can improve tissue perfusion and increase energy synthesis in enterocytes, decrease endoplasmic reticulum stress (ERS) and improve mucin and ITF synthesis. Finally, lessen intestinal mucus barrier damage after burn injury.


[Freud, Fliess, and the parenthood of psychoanalysis].
Although Freud attributed his self analytic interest and revived oedipal conflict to the death of his father, his biopsychological parenthood was also a significant determinant. Freud fathered six children, reactivating his own childhood and infantile unconscious conflicts and fantasies. His idealization of Fliess began with his own fatherhood, and the interruption of his exclusive relationship with his wife, and unconsciously his mother. His enlarging family evoked his mother's pregnancies and the birth of his seven siblings. Freud identified with his fertile parents and envied his sibling rivals. The experience of having five sisters in succession (after the death of his brother Julius) was of great importance. Freud's mother and sisters have been protectively veiled in his associations, with biographical and theoretical implications. Freud creatively analyzed himself, encountering and explaining the childhood past in his present life, as he became the father of psychoanalysis.


Considerations for implantation site of VX2 carcinoma into rabbit liver.
To assess whether the implantation site of VX2 carcinoma into rabbit liver affects successful vessel selection for transcatheter arterial interventions. Twenty-four New Zealand White rabbits were randomly assigned to two groups. All implantations were performed by open laparotomy with minced tumor cells inserted into a 16-gauge Angiocath needle. Group I rabbits (n = 12) had tumor implanted into the left medial lobe of the liver and group II rabbits (n = 12) had tumor implanted into the left lateral lobe. Two weeks after implantation, selective angiography was performed for subsequent chemoembolization, which was part of a different study. Tested variables included maximum tumor diameter, tumor feeding artery size, and tumor vascularity. Successful tumor growth was achieved in all rabbits. Selective angiography was possible in 33.3% of rabbits in group I and 66.6% of rabbits in group II (P < .05). Tumor size and vascularity were similar between groups. Mean lengths of tumor feeder arteries from the bifurcation of the left hepatic artery were 4.1 mm +/- 1.2 in group I (left medial lobe) and 10.8 mm +/- 3.0 in group II (left lateral lobe; P < .05). The angulation of the left medial lobar artery (group I) off the left hepatic artery was acute in eight of 12 rabbits (66.6%), but only four of 12 rabbits in group II (33.3%) showed acute angulation of the left lateral lobar artery off the left hepatic artery (P < .05). Mean angiography time was significantly shorter in group II. For selective hepatic arterial interventions, the left lateral lobe of the liver may be favorable as an implantation site for VX2 tumors in rabbits.


Differential localization of calmodulin-dependent enzymes in rat brain: evidence for selective expression of cyclic nucleotide phosphodiesterase in specific neurons.
High-affinity antibodies against calmodulin (CaM)-dependent cyclic nucleotide phosphodiesterase and protein phosphatase (calcineurin) were purified and characterized. Rabbit anti-phosphodiesterase antibody did not react with other phosphodiesterases or with the regulatory subunits of cAMP-dependent protein kinase. Affinity-purified goat anti-calcineurin antibody recognized both the 61-kDa catalytic subunit and the 18-kDa Ca2+-binding subunit of the phosphatase. Neither antibody reacted with CaM, several CaM-binding proteins (calmodulin-dependent protein kinase, myosin light chain kinase, fodrin), or other cytosolic proteins from brain. The antibodies were used to compare the cellular localization of these two CaM-dependent enzymes in rat brain. Both calcineurin and phosphodiesterase were found predominantly in nerve cells; however, phosphodiesterase was restricted to very specific neuronal populations. Phosphodiesterase was prominent in the somatic cytoplasm and dendrites of regional output neurons--e.g., cerebellar Purkinje cells and hippocampal and cortical pyramidal cells. The extensive and uniform staining in the dendrites was consistent with postsynaptic localization and suggested an important function for this enzyme in neurons that integrate multiple convergent inputs. Calcineurin was present in virtually all classes of neurons, with immunoreactivity confined primarily to cell bodies. Both diffuse cytoplasmic staining and characteristic punctate staining of cell bodies were observed; the latter suggested compartmentalization of calcineurin at or near the plasma membrane. The results of this study demonstrate that calcineurin and phosphodiesterase are differentially localized in the central nervous system. Thus, the expression and compartmentalization of CaM-binding proteins may be highly regulated and specific for particular differentiated nerve cell types.


Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP).
Our goal was to review the safety and effectiveness of available antiemetics for treatment of nausea and vomiting of pregnancy. We performed a quantitative and qualitative overview of observational controlled studies for drug safety in pregnancy and randomized controlled trials for drug effectiveness for nausea and vomiting in pregnancy. All of the following are safe and effective for treatment of varying degrees of nausea and vomiting in pregnancy: Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine), antihistamine (H(1)) blockers, and phenothiazines; however, the magnitude of effect, particularly for phenothiazines, is in question and may differ among individual agents. Pyridoxine and vitamin B(12)are safe and may be effective. Metoclopramide, droperidol, and ondansetron may be effective, but safety data are insufficient to recommend them as first-line agents. Corticosteroids may not be as beneficial as first thought, and there may be a small teratogenic risk. The relative effectiveness of various agents is largely unknown. Many medications, particularly H(1)-antagonists and phenothiazines, are safe and effective for treatment of varying degrees of NVP.


Growth faltering lacks association with the distribution of first year deaths.
A retrospective study of infant mortality from death registers was made in St Lucia and St Vincent. In both islands postneonatal deaths by month were found to be evenly distributed throughout the first year although the total infant mortality rates differed widely. The growth of a cohort of children from three St Lucian villages was studied. Their weight curve showed 'faltering' at 3 months, closely resembling the developing world pattern described by Waterlow, Ashworth & Griffiths (1980). We therefore conclude that there is no necessary association between this pattern of infant growth and infant mortality rate, nor between the distribution of weight velocity and the distribution of deaths in the first year.


What controls the magnetic exchange interaction in mixed- and homo-valent Mn7 disc-like clusters? A theoretical perspective.
Density functional theory (DFT) studies have been undertaken to compute the magnetic exchange and to probe the origin of the magnetic interactions in two hetero- and two homo-valent heptanuclear manganese disc-like clusters, of formula [Mn(II) 4 Mn(IV) 3 (tea)(teaH2 )3 (peolH)4 ] (1), [Mn(II) 4 Mn(III) 3 F3 (tea)(teaH)(teaH2 )2 (piv)4 (Hpiv)(chp)3 ] (2), [Mn(II) 7 (pppd)6 (tea)(OH)3 ] (3) and [Mn(II) 7 (paa)6 (OMe)6 ] (4) (teaH3 =triethanolamine, peolH4 =pentaerythritol, Hpiv=pivalic acid, Hchp=6-chloro-2-hydroxypyridine, pppd=1-phenyl-3-(2-pyridyl) propane-1,3-dione; paaH=N-(2-pyridinyl)acetoacetamide). DFT calculations yield J values, which reproduce the magnetic susceptibility data very well for all four complexes; these studies are also highlighting the likely ageing/stability problems in two of the complexes. It is found that the spin ground states, S, for complexes 1-4 are drastically different, varying from S=29/2 to S=1/2. These values are found to be controlled by the nature of the oxidation state of the metal ions and minor differences present in the structures. Extensive magneto-structural correlations are developed for the seven building unit dimers present in the complexes, with the correlations unlocking the reasons behind the differences in the magnetic properties observed. Independent of the oxidation state of the metal ions, the Mn-O-Mn/Mn-F-Mn angles are found to be the key parameters, which significantly influence the sign as well as the magnitude of the J values. The magneto-structural correlations developed here, have broad applicability and can be utilised to understand the magnetic properties of other Mn clusters.


Demonstration of two distinct forms of released low affinity-type rat IL-2 receptors.
The release of IL-2 binding proteins, derived from the 55,000 MW low affinity IL-2R (L chain), has been observed for virtually all L chain-bearing cells in either humans, the mouse or the rat. Based on the characterization of the released human L chain as a molecule 10,000 MW smaller than the cell surface receptor, either proteolytic cleavage or differential splicing of the L chain encoding mRNA have been suggested as mechanisms underlying the receptor release. Combining affinity labelling of the L chain with [125I]IL-2 and immunoprecipitation with L chain-specific monoclonal antibody (mAb) applied for the detection of soluble rat IL-2R revealed the existence of two classes of soluble receptors, one being of the same size as cell surface-expressed L chain, the other of 40,000 apparent molecular mass. These findings raise the possibility of other mechanisms of receptor release than those discussed for human L chain.


Isolation, characterization, cloning and expression of an alpha-neurotoxin from the venom of the Mexican coral snake Micrurus laticollaris (Squamata: Elapidae).
A new member of short chain α-neurotoxic protein family from venom of the Mexican coral snake, Micrurus laticollaris, was characterized. This protein, named MlatA1, possesses 61 amino acids with 8 conserved cysteine residues, sharing 30-91% sequence identity with other fully sequenced Micrurus toxins. MlatA1 (LD50i.v. = 0.064 mg/kg) antagonizes with both fetal and adult nicotinic acetylcholine receptor (nAChR) as well as α-7 neuronal nAChR in a dose-dependent way. Specific rabbit anti-Mlat serum (titer higher than 18,000) does not show any protective ability against this toxin, nevertheless it was able to recognize protein bands in six out of twelve Micrurus venoms showing the existence of two distinct antigenic groups for α-neurotoxins in North American coral snakes species. The MlatA1 gene was cloned and used to produce recombinant toxin (rMlatA1) that was recognized by rabbit anti-native toxin but was depleted of toxic activity.


Assessment of the specificity of cytotoxic T lymphocytes for the nucleoprotein of Pichinde virus using recombinant vaccinia viruses.
Pichinde virus (PV) infection of mice results in induction of a strong H-2 restricted, virus-specific cytotoxic T lymphocyte (CTL) response and rapid clearance of the virus. To define the specificities of CTL induced by PV infection, we constructed vaccinia virus recombinants containing cloned cDNAs corresponding to full-length (VVNP) and a truncated form (VVNP 51-561) of the nucleoprotein (NP) gene of PV. Radioimmunoprecipitation analysis of infected cell lysates indicated that VVNP expressed a PV-specific product identical in size to that of authentic NP, while vaccinia virus recombinants containing truncated NP produced a polypeptide consistent with the synthesis of amino acids 51-561 of Pichinde virus NP. Interestingly, cells infected with VVNP synthesized easily detectable, but much lower levels of nucleoprotein relative to both PV and VVNP51-561. Primary virus-specific CTL induced in three different strains of inbred mice following intravenous infection with PV were able to lyse syngeneic target cells infected with PV but did not markedly lyse syngeneic targets expressing full-length or truncated NP following recombinant vaccinia virus infection. Similarly, secondary anti-PV specific CTL generated following in vitro restimulation by PV or selectively restimulated with vaccinia recombinants did not significantly lyse target cells expressing NP. Further, infection of mice with VVNP and VVNP51-561 did not induce CTLs specific for PV and did not prime mice for the generation of memory anti-PV CTL in vivo. These results suggest that PV gene products other than NP, such as the GPC or L protein, contain the major target epitope(s) recognized by PV-specific CTL.


Prevalence of low-grade inflammation in depression: a systematic review and meta-analysis of CRP levels.
Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis. We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L). After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21-34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22-1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47-69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18-1.82). About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.


Acute angle closure attack after an intravitreal bevacizumab injection for branch retinal vein occlusion: a case report.
Intravitreal injection is widely used to treat retinal vein occlusion, and acute angle closure (AAC) is an exceptional complication of intravitreal injection. The authors report a case of AAC that occurred immediately after administering intravitreal bevacizumab to treat branch retinal vein occlusion (BRVO). A 65-year-old woman was referred to the retina clinic of a tertiary referral center for the treatment of macular edema secondary to BRVO. On slit lamp examination, anterior chamber (AC) depth was shallow (3 corneal thicknesses centrally, 1/4 corneal thicknesses peripherally) in both eyes. Intraocular pressure (IOP) was 19 mmHg in both eyes, and refractive error was +1.00 diopter sphere in both eyes. A gonioscopy exam demonstrated narrow angle of over 180° in both eyes. To treat the macular edema, bevacizumab was injected into her right eye intravitreally. After two bevacizumab injections, the macular edema regressed but recurred 5 months later, and thus, a third injection was performed. The next day, she visited our emergency department complaining of persistent ocular pain in her right eye. The right pupil had dilated to 6 mm diameter and was fixed. Slit lamp exam revealed diffuse corneal edema in her right eye, which had an IOP of 56 mmHg. After administration of intravenous mannitol, the IOP fell to 14 mmHg and the corneal edema disappeared. Subsequently, a glaucoma specialist performed laser iridotomy on the right eye. Although AAC is a rare complication of intravitreal injection, it can occur in a patient with risk factors such as hyperopic eye or narrow angle.


Effect of Surface Treatment with Er;Cr:YSSG, Nd:YAG, and CO2 Lasers on Repair Shear Bond Strength of a Silorane-based Composite Resin.
Background and aims. The aim of the present study was to compare the effect ofsurface treatment with Er; Cr:YSSG, Nd:YAG, and CO2 lasers on repair shear bond strength of a silorane-based composite resin. Materials and methods. Sixty eight cylindrical samples of a silorane-based composite resin (Filtek Silorane) were pre-pared and randomly divided into 4 groups as follows: group 1: without surface treatment; groups 2, 3 and 4 with surface treatments using Er; Cr:YSSG, Nd:YAG, and CO2 lasers, respectively. A positive control group (group 5) was assigned in order to measure cohesive strength. Repair shear bond strength values were measured and data was analyzed using one-way ANOVA and a post hoc Tukey test at a significance level of α=0.05. Results. There were statistically significant differences in repair shear bond strength values between group 2 and other groups (P < 0.05); and between group 1and groups 3and 4 (P < 0.001); however, there were no significant differences be-tween groups 3 and 4 (P = 0.91). Conclusion. The repair shear bond strength of silorane-based composite resin was acceptable by surface treatment with lasers.


Cerebral Whipple's disease. Diagnosis by brain biopsy.
Whipple's disease, a multisystem chronic granulomatous disease treatable by antibiotics, usually presents clinically with gastrointestinal or joint symptoms. Usually, the diagnosis is substantiated by small intestinal biopsy. This shows diastase-resistant periodic-acid-Schiff-(PAS)-positive inclusions in the cytoplasm of macrophages within the lamina propria. By electron microscopy, this PAS-positive material consists of 1.5 X 0.2-mum bacilli and fine fibrillar material within macrophage phagolysosomes. Rarely, Whipple's disease presents clinically as a primary neurologic disease without gastrointestinal symptoms. Because untreated cerebral Whipple's disease usually progresses rapidly to death, it is imperative to establish the diagnosis promptly. This report describes a case of cerebral Whipple's disease without gastrointestinal symptoms that was diagnosed early by light-and electron-microscopic study of brain biopsy material.


Cardiovascular responses of exercises performed within the extreme exercise domain.
Stroke volume (SV), heart rate (HR) and arterio-venous O2 difference (a-vO2diff) responses to heavy and severe-intensity exercise have been well documented; however, there is a lack of information on the SV, HR and a v-O2diff responses of work rates within extreme exercise domain. The aim of this study was, therefore, to focus on central and peripheral components of VO2 responses to exercises performed within the heavy, severe and extreme exercise domain. Eight well-trained male cyclists participated in this study. Maximal O2 consumption (VO2max) and corresponding work rate (P@VO2max) were determined by multisession constant work rate exercises. Cardiovascular responses to exercises were evaluated by nitrous-oxide rebreathing method with work rates from 40 % to 160 % of P@VO2max, VO2max corresponded to 324+/-39.4 W; however, maximal SV responses occurred at 205+/-54.3 W (p<0.01). Maximal cardiac output (Q), HR, and a vO2diff responses were revealed by the P@VO2max. VO2 response to exercise significantly decreased from severe-intense exercises to the first work rate of extreme exercise domain due to significant decreases in Q, SV, and HR responses (p<0.05), except a v-O2diff (p>0.05). Moreover, non-significant decreases in Q, SV, and a v-O2diff were evaluated as response to increase in work rate belonging to extreme work rates (p>0.05), except the HR (p<0.05). Work rates within the lower district of the extreme exercise domain have an important potential to improve peripheral component of VO2, while the P@VO2max seems the most appropriate intensity for aerobic endurance development as it maximizes the central component of VO2max.


Ibuprofen inhibits the synaptic failure induced by the amyloid-β peptide in hippocampal neurons.
Epidemiological studies have reported a decrease in the prevalence of Alzheimer's disease in individuals who chronically use non-steroidal anti-inflammatory drugs (NSAIDs). Clinical trials, on the other hand, have been less positive. Nevertheless, it has been proposed that NSAIDs exert part of their effects by reducing long-term cerebral neuroinflammation, although this mechanism has not been proven. In this study, we report that ibuprofen, one of the more widely used non-steroidal anti-inflammatory drugs, was able to alter the ultrastructure of amyloid-β peptide (Aβ) and significantly decrease its association to neuronal membranes, and consequently, its synaptotoxic effect in rat primary hippocampal and cortical cultures at 24 h incubation. In agreement with these results, we found that the decrease in the frequency of calcium transients with Aβ was partly recovered by addition of ibuprofen (8.0 × 10-2 Hz in control; 3.4 × 10-2 Hz in 5 μM Aβ, and 5.9 × 10-2 Hz in the presence of Aβ and 200 μM ibuprofen). Additionally, this effect correlated well with the increment and recovery of miniature spontaneous currents (47 ± 5% of control in 1 μM Aβ alone and 104 ± 14% in the presence of Aβ and ibuprofen). Our results suggest that ibuprofen could be exerting its neuroprotective effect by directly interacting with Aβ and altering its toxic aggregated forms. We postulate that other ibuprofen analogs with better pharmacological properties might have a higher efficacy in AD.


[Automobile versus pedestrian accidents analysis by fixed-parameters computer simulation].
Using computer simulation to analyze the effects of speed, type of automobile and impacted position on crash-course and injuries of pedestrians in automobile vs. pedestrian accidents. Automobiles (bus, minibus, car and truck) and pedestrian models were constructed with multi-body dynamics computing method. The crashes were simulated at different impact speeds (20, 30, 40, 50 and 60 km/h) and different positions (front, lateral and rear of pedestrians). Crash-courses and their biomechanical responses were studied. If the type of automobile and impact position were the same, the crash-courses were similar (impact speed < or = 60 km/h). There were some characteristics in the head acceleration, upper neck axial force and leg axial force. Multi-body dynamics computer simulation of crash can be applied to analyze crash-course and injuries (head, neck and leg) of pedestrians.


Expression of the recombinant protein disulphide isomerase of Teladorsagia circumcincta.
The aim of this experiment was to find an antigen from Teladorsagia circumcincta to measure the level of IgA in ovine serum samples. Previous experiments used the titre of IgA to select sheep resistant to infection with T. circumcincta. By Western blotting 22 experimentally infected ewes recognized many proteins, but not all of them were recognized by all animals. Sheep were divided into two groups of animals: those that recognized a protein in Western blotting and those that did not. Among all proteins, three showed significant associations between protein recognition and the titre of IgA in the serum.


Ecological correlation among prevalence of asthma symptoms, rhinoconjunctivitis and atopic eczema with notifications of tuberculosis and measles in the Brazilian population.
This study aims to assess the relationship among incidence of tuberculosis and measles, in the general population, within the year of birth and the prevalence of asthma, rhinoconjunctivitis and atopic eczema in teenagers from different Brazilian cities enrolled in the International Study of Asthma and Allergies in Childhood (ISAAC) phases I and III. Positive answers to the questions: 'Have you had wheezing or whistling in the chest in the past 12 months?', 'In the past 12 months, has this nose problem been accompanied by itchy-watery eyes?' and 'Has this itchy rash at any time affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears or eyes?' identified the teenagers with asthma, rhinoconjunctivitis, and atopic eczema, respectively. The incidence of tuberculosis and measles, in the general population, observed in the year of birth of the enrolled teenagers (1981/82 and 1988/89) were obtained from governmental agencies: National Foundation of Health (FUNASA) and Brazilian Institute of Geography and Statistics (IBGE). They were compared with the prevalence of asthma, rhinoconjunctivitis and atopic eczema reported in both ISAAC phases I and III. Although we observed reduction of the incidence of tuberculosis and measles in the general population in all cities, the prevalence of asthma, rhinoconjunctivitis and atopic eczema remained stable in most of the centers. In Pernambuco and Paraná, there has been a significant increase in the prevalence of rhinoconjunctivitis. These data do not corroborate the findings of an inverse relationship between the prevalence of atopic diseases and the decreasing incidence of tuberculosis and measles.


Pancreaticoduodenectomy for gallbladder cancer with peripancreatic nodal metastases.
The prognosis of patients with advanced gallbladder carcinoma remains dismal. In the English language literature, we found only one 5-year survivor with peripancreatic lymph node metastases. We herein report a patient with marked peripancreatic nodal metastases, who has exhibited the longest survival (6 years) without recurrence after a pancreaticoduodenectomy combined with extended cholecystectomy. This outcome suggests that pancreaticoduodenectomy may be effective for clearance of peripancreatic nodal metastases from gallbladder cancer.


Partial-Interpenetration-Controlled UiO-Type Metal-Organic Framework and its Catalytic Activity.
An unprecedented correlation between the catalytic activity of a Zr-based UiO-type metal-organic framework (MOF) and its degree of interpenetration (DOI) is reported. The DOI of an MOF is hard to control owing to the high-energy penalty required to construct a partially interpenetrated structure. Surprisingly, strong interactions between building blocks (inter-ligand hydrogen bonding) facilitate the formation of partially interpenetrated structures under carefully regulated synthesis conditions. Moreover, catalytic conversion rates for cyanosilylation and Knoevenagel condensation reactions are found to be proportional to the DOI of the MOF. Among MOFs with DOIs in the 0-100% range, that with a DOI of 87% is the most catalytically active. Framework interpenetration is known to lower catalytic performance by impeding reactant diffusion. A higher effective reactant concentration due to tight inclusion in the interpenetrated region is possibly responsible for this inverted result.


Pyrrolopyrimidines: novel brain-penetrating antioxidants with neuroprotective activity in brain injury and ischemia models.
A novel group of antioxidant compounds, the pyrrolopyrimidines, has been discovered recently. Many of these possess significantly improved oral bioavailability (56-70% in rats), increased efficacy and potency in protecting cultured neurons against iron-induced lipid peroxidative injury and as much as a 5-fold increase in brain uptake compared with the 21-aminosteroid antioxidant compound, tirilazad mesylate (U-74006F), described earlier. They appear to quench lipid peroxidation reactions by electron-donating and/or radical-trapping mechanisms. Several compounds in the series, such as U-101033E and U-104067F, demonstrate greater ability than tirilazad to protect the hippocampal CA1 region in the gerbil transient (5-min) forebrain ischemia model. Delaying treatment until 4 hr after the ischemic insult still results in significant CA1 neuronal protection. U-101033E is still effective in salvaging a portion of the CA1 neuronal population when the ischemic duration is extended to 10 min. In addition, U-101033E has been found to be protective in the context of focal cerebral ischemia, reducing infarct size in the mouse permanent middle cerebral artery occlusion model, in contrast to tirilazad which is minimally effective. These results suggest that antioxidant compounds with improved brain parenchymal penetration are better able to limit certain types of ischemic brain damage than those which are localized in the cerebral microvasculature. However, the activity of U-101033E in improving early post-traumatic recovery in mice subjected to severe concussive head injury is similar to that of tirilazad. Last, the oral bioavailability of many pyrrolopyrimidines suggests that they may be useful for certain chronic neurodegenerative disorders in which lipid peroxidation plays a role.


Social perception and aging: The relationship between aging and the perception of subtle changes in facial happiness and identity.
Previous findings suggest that older adults show impairments in the social perception of faces, including the perception of emotion and facial identity. The majority of this work has tended to examine performance on tasks involving young adult faces and prototypical emotions. While useful, this can influence performance differences between groups due to perceptual biases and limitations on task performance. Here we sought to examine how typical aging is associated with the perception of subtle changes in facial happiness and facial identity in older adult faces. We developed novel tasks that permitted the ability to assess facial happiness, facial identity, and non-social perception (object perception) across similar task parameters. We observe that aging is linked with declines in the ability to make fine-grained judgements in the perception of facial happiness and facial identity (from older adult faces), but not for non-social (object) perception. This pattern of results is discussed in relation to mechanisms that may contribute to declines in facial perceptual processing in older adulthood.


The evaluation of the colour changes of traditional composites, ceramic blocks and cad/cam composites in different solutions.
The aim of this study is to investigate the color changes of three different traditional composites, one ceramic and two resin-based composites CAD/CAM blocks in different solutions. The materials used in the study were CAD/CAM block containing lithium disilicate glass ceramic (Ivoclar), Vita Enamic containing resin (VITA), Lava Ultimate Block containing resin (3M ESPE), G-aenial anterior composite (GC,), Filtek™ Ultimate Universal composite (3M ESPE) and Clearfil Majesty Esthetic composite (Kuaray). As colouring solutions, red wine (Buzbaǧ), black tea (Lipton), coffee (Nescafe) and distilled water (EAU distillee) were used. For the preparation of the traditional composite samples to be used in the study, 7 × 7 mm square-shaped plexiglass moulds, 1.2 mm in thickness, were used. The CAD/CAM blocks with ceramic and resin content were cut at the same thickness using a Struers sensitive cutting device. The samples were then randomly separated into grups of 10 and of the 240 samples, groups were separated into 6 different materials and 4 different solutions. The colour measurements of the 240 samples were taken at baseline, 30 days and 120 days with a Lovibond spectrophotometer (Tintometer). A statistically significant difference was determined between the materials in respect of the ΔE values in the 30-day solution groups (P < 0.05). No statistically significant difference was determined in the ΔE values of the different materials in the 30-day and 120-day distilled water groups (P > 0.05). A statistically significant difference was determined between the materials in respect of the ΔE values in the 120-day solution groups (P < 0.05). In respect of discolouration, ceramic blocks are more successful. Resin-based blocks and traditional aesthetic composites showed more discolouration. The dietary habits of the patient should be taken into consideration in the selection of the restorative material.


The ATC1 gene encodes a cell wall-linked acid trehalase required for growth on trehalose in Candida albicans.
After screening a Candida albicans genome data base, the product of an open reading frame (IPF 19760/CA2574) with 41% identity to Saccharomyces cerevisiae vacuolar acid trehalase (Ath1p) was identified and named Atc1p. The deduced amino acid sequence shows that Atc1p contains an N-terminal hydrophobic signal peptide and 20 potential sites for N-glycosylation. C. albicans homozygous mutants that lack acid trehalase activity were constructed by gene disruption at the two ATC chromosomal alleles. Analysis of these null mutants shows that Atc1p is localized in the cell wall and is required for growth on trehalose as a carbon source. An Atc1p endowed with acid trehalase activity was obtained by an in vtro transcription-translation coupled system. These results strongly suggest that ATC1 is the structural gene encoding cell wall acid trehalase in C. albicans. Determinations of ATC1 mRNA expression as well as acid trehalase activity in the presence and absence of glucose point out that ATC1 gene is regulated by glucose repression.


[Unusual cases of maternal death caused by amniotic fluid embolism].
Five cases of amnion fluid embolism are reported. In the first case the cause of the death was the obstruction of the lung-vessels. In the lung tissue calcium embolia could also been detected. In the second case embolization started--at unruptured amnionsac--with ecclampsia-like convulsions, later it was followed by coagulopathia. In the third case amnion fluid embolism was complicated by coagulopathia. In the fourth case in addition to amnion fluid embolism endometritis purulenta complicated by endotoxinaemia and coagulopathia were also present. In all four cases rupture of the uterus was revealed. In the fifth case amnion fluid embolism developed without the rupture of the uterus. At the autopsy of cases of maternal death the possibility of amnion fluid embolism should always be considered. Although macroscopic changes seen at amnion fluid embolism are not pathognomic, when clinical and pathological symptoms of haemorrhagic diathesis are present, there always arises the suspicion of amnion fluid embolism. Since lungs are relatively resistant to putrefaction amnion fluid embolism in optimal cases can be diagnosed histologically even in exhumated lung specimen. Reliable diagnosis of amnion fluid embolism in cases of sudden maternal death gives possibility to exclude medical negligence.


Comparison of the sensitivity and specificity of 5 image sets of dual-energy computed tomography for detecting first-pass myocardial perfusion defects compared with positron emission tomography.
The sensitivity and specificity of 5 different image sets of dual-energy computed tomography (DECT) for the detection of first-pass myocardial perfusion defects have not systematically been compared using positron emission tomography (PET) as a reference standard. Forty-nine consecutive patients, with known or strongly suspected of coronary artery disease, were prospectively enrolled in our study. Cardiac DECT was performed at rest state using a second-generation 128-slice dual-source CT. The DECT data were reconstructed to iodine maps, monoenergetic images, 100 kV images, nonlinearly blended images, and linearly blended images by different postprocessing techniques. The myocardial perfusion defects on DECT images were visually assessed by 5 observers, using standard 17-segment model. Diagnostic accuracy of 5 image sets was assessed using nitrogen-13 ammonia PET as the gold standard. Discrimination was quantified using the area under the receiver operating characteristic curve (AUC), and AUCs were compared using the method of DeLong. The DECT and PET examinations were successfully completed in 30 patients and a total of 90 territories and 510 segments were analyzed. Cardiac PET revealed myocardial perfusion defects in 56 territories (62%) and 209 segments (41%). The AUC of iodine maps, monoenergetic images, 100 kV images, nonlinearly blended images, and linearly blended images were 0.986, 0.934, 0.913, 0.881, and 0.871, respectively, on a per-territory basis. These values were 0.922, 0.813, 0.779, 0.763, and 0.728, respectively, on a per-segment basis. DECT iodine maps shows high sensitivity and specificity, and is superior to other DECT image sets for the detection of myocardial perfusion defects in the first-pass myocardial perfusion.


Enhanced generation of leukotriene B4 from calcium ionophore-stimulated rat peritoneal inflammatory cells: a possible clinical relevance.
Leukotrienes (LTs) producing capacity was investigated in calcium ionophore A23187-stimulated peripheral white blood cells and peritoneal inflammatory cells suspension isolated from the same rat. A reverse phase high performance liquid chromatography technique and computerized UV spectroscopy were employed to isolate and quantitate the released LTs namely, LTC(4) and LTB(4). Preincubation of rat peritoneal inflammatory cells at 37 degrees C for 5 min followed by calcium ionophore A23187 stimulation for another 5 min produced significantly elevated amounts of LTB(4) as compared to peripheral white blood cells isolated from the same rat (103+/-12.7 versus 40+/-3.6 pmol/10(7) cells, respectively; mean+/-SEM). Enhanced generation of LTB(4) was associated with production of similar amounts of LTC(4) as compared with LTC(4) produced by peripheral white blood cells (15.2+/-4.2 versus 14.6+/-2 pmol/10(7) cells, respectively). In subsequent experiments, when peritoneal inflammatory cells and white blood cells suspension isolated from the same rats were stimulated with calcium ionophore A23187 (1 micro M) after preincubation with different concentrations of exogenous arachidonic acid (1, 3 and 10 micro M), significantly higher amounts of LTB(4) were produced by the peritoneal inflamed cells while a similar amounts of LTC(4)were produced by both types of cells. Increased LTB(4) formation by rat peritoneal inflammatory cells may prove to be of pathophysiological relevance, since this compound has been described to play an important role in acute inflammatory reaction.


The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus and associated risk factors among adults living in a rural Koladiba town, northwest Ethiopia.
Diabetes mellitus is becoming a big public health challenge, particularly in developing countries like Ethiopia. It is a manageable disease if early screening and follow up is made. However, as studies in Ethiopia are limited and unorganized, determining the magnitude of prediabetes and diabetes and identifying associated risk factors is quite essential. A community-based, cross-sectional study was conducted from February to April 2015 among adults (aged ≥20 years) in a rural Koladiba town. A multistage sampling technique was used to select a total of 392 study participants. Data were collected after a fully informed written consent was obtained from each participant. Demographic, behavioral, and clinical data were collected using a well-structured questionnaire. Multivariable logistic regression models were fitted to control the effect of confounders. Adjusted odds ratios (AOR) with their 95% confidence intervals (95% CI) were computed to measure associations. A p value of <0.05 was considered as statistically significant. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus were 12% (95% CI 9-16) and 2.3% (95% CI 1.1-4), respectively, in Koladiba. Overweight (AOR: 4.257, 95% CI 1.345-13.476), obesity (AOR: 5.26, 95% CI 1.138-24.316), hypertriglyceridemia (AOR: 2.83, 95% CI 1.451-5.521), and systolic hypertension (AOR: 3.858, 95% CI 1.62-9.189) were found to be independently associated with impaired fasting glucose. Positive family history of diabetes also showed a marginal association with impaired fasting glucose (p = 0.057). Male sex (p = 0.012) and hypertriglyceridemia (p = 0.030) were associated with undiagnosed diabetes mellitus. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus are found to be significant. Obesity, hypertriglyceridemia, and systolic hypertension are independently associated with impaired fasting glucose among adults. We recommend that the community be aware of healthy life style, early screening, and maintain continuous follow up.


Circulating mircoRNA-21 as a predictor for vascular restenosis after interventional therapy in patients with lower extremity arterial occlusive disease.
The present study was designed to investigate the role of circulating miRNA-21 (miR-21) in vascular restenosis of lower extremity arterial occlusive disease (LEAOD) patients after interventional therapy. A total of 412 LEAOD patients were enrolled randomly in the present study. According to computed tomography angiography (CTA) and ankle-brachial index (ABI), patients were assigned into the restenosis group and the non-restenosis group. miR-21 expression was detected with quantitative real-time PCR (qRT-PCR) before and after patients underwent interventional therapy. A follow-up period of 6 months was achieved. A receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to assess the predictive value of miR-21 in vascular restenosis. Patients were older in the restenosis group than in the non-restenosis group. The percentages of patients with diabetes and hypertension were higher in the restenosis group than in the non-restenosis group, and the Fontaine stage exhibited a significant difference between the two groups. miR-21 expression was higher in the restenosis group than in the non-restenosis group. miR-21 expression level was related to age, diabetes and hypertension in the restenosis group. Using miR-21 to predict vascular restenosis yielded an AUC of 0.938 (95% confidence interval (CI): 0.898-0.977), with Youden index of 0.817, sensitivity of 83.5% and specificity of 98.2%. Logistic regression analysis revealed that diabetes and miR-21 expression were the major risk factors for vascular restenosis of LEAOD. miR-21 can be used as a predictive indicator for vascular restenosis of LEAOD after interventional therapy.


Perspectives of being spouse, parent, and surgeon.
Achieving a balance between one's career and personal life is a never-ending challenge. As a surgeon, add-on cases and double-booked clinics can lead to long hours at work and make availability for family time unpredictable. It may seem like the threat of interruption because of patient needs always loom. Disruptions to family time extend beyond the long hours spent in surgery and clinics. Inattentiveness at home because of the technology tethers that keep one available for constant questions and patient care issues can also distract from time spent with family. Although the practice of an orthopaedic trauma surgeon can involve unpredictable schedules and patient care issues, there are means of mitigating the chaos that can envelop one's personal life as a result of a chosen career track. Clear priorities and expectations in both personal and professional arenas can improve the work-life balance. Flexible jobs that allow for more time with family do exist. Negotiating for this flexibility and self-assurance in holding fast to personal ideals are important in achieving a successful balance.


Identifying frailty in the Emergency Department-feasibility study.
identifying the most at risk older people in Emergency Departments (EDs) may help guide clinical practice, and service improvement in emergency care, but little is known about how to implement such tools in practice. consensus building was used to determine the desirable characteristics of a risk stratification process, including focus groups and literature reviewing. Candidate tools were tested using clinical vignettes in semi-structured interviews with a range of clinicians working in one large ED, assessing speed of use, ease of use and agreement with clinical judgement. The primary outcome was the likelihood of future use of a given frailty tool. the ideal tool characteristics included brevity (<1 min), simplicity and multidimensionality; tools selected for testing included the Identification of Seniors At Risk, Clinical Frailty Scale, PRISMA-7 and Silver Code. One hundred and twenty-one staff members (43% of the total ED workforce) were recruited from one large ED in the East Midlands. Two hundred and thirty-six individual frailty tool assessments were undertaken using 1 of 10 clinical vignettes; 75% of staff stated that they would use at least one of the tools again, with no significant differences between the individual tools. The median time to complete the tool was around 1 min per patient for all four tools. There were no significant differences in timing, ease of use or agreement with clinical judgement between tools. validated risk stratification tools are quick, simple, easy to use and 75% of staff would use the tools again in the future.


Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer.
Reactive oxygen species (ROS)-based photodynamic therapy (PDT) has a widespread application in cancer therapy. Nevertheless, the efficiency of PDT is far from satisfactory. One major impediment is the overexpression of glutathione (GSH) in tumor cells, which could deplete the level of PDT-generated ROS. Herein, we develop a novel type of cytochrome P450 enzyme-mediated auto-enhanced photodynamic co-nanoassembly between clopidogrel (CPG) and photosensitizer pyropheophorbide a (PPa). Methods: In this work, we prepare the co-assembled nanoparticles of CPG and PPa (CPG/PPa NPs) by using one-step precipitation method. The assembly mechanism, drug release behavior, GSH consumption, ROS generation, cellular uptake, cytotoxicity of CPG/PPa NPs are investigated in vitro. The mice bearing 4T1 tumor are employed to evaluate in vivo biodistribution and anti-tumor effect of CPG/PPa NPs. Results: Such CPG/PPa NPs could disrupt the intracellular redox homeostasis, resulting from the elimination of GSH by CPG active metabolite mediated by cytochrome P450 enzyme (CYP2C19). The in vivo assays reveal that CPG/PPa NPs not only increase the drug accumulation in tumor sites but also significantly suppress tumor growth in BALB/c mice bearing 4T1 tumor. With CPG-mediated GSH consumption and PPa-triggered ROS generation, CPG/PPa NPs show the enhanced PDT treatment effect by breaking intracellular redox balance. Conclusion: Our findings provide a valuable knowledge for the rational design of the PDT-based combinational cancer therapy.


[The effect of intraperitoneal and intra-aortic chemotherapy for unresectable gastric cancer].
Regional chemotherapy was given 16 unresectable gastric cancer patients. Two types of the chemotherapy, intraperitoneal (IP) and intraaortic (IA) administration, were carried out. The control group was comprised of 17 patients. The response of the chemotherapy for primary tumor was 36.4% in the IP group and 20% in the IA one. Among these patients, 2 of 11 in IP and 1 of 5 in IA were able to resect the primary tumor. The 50% survival time of IP, IA and control was 347, 227 and 78 days, respectively. One-year survival rates of IP, IA and control were 68%, 29% and 0%, respectively. IP showed a significantly longer survival rate than controls (p < 0.001). All but one patient was able to stay at home. Intraperitoneal chemotherapy showed both local and systemic effects in unresectable gastric cancer.


[Anti-IL-6 : new therapeutic trends].
The anti-IL-6 tocilizumab is a recognized treatment in rheumatoid arthritis and in systemic juvenile idiopathic arthritis. Almost ten years after its first use, there is more information about its security profile and its indication should be extended to other systemic inflammatory diseases, such as the giant cell arteritis. New molecules targetting the IL-6 pathway are under validation : sarilumab, sirukumab and olokizumab. Here is a brief state of the future outlook and trends of this therapeutic class.


Transcatheter Mitral Valve Implantation: Current Status and Future Perspectives.
Mitral transcatheter therapies represent the treatment of choice for all patients deemed unsuitable for cardiac surgery. So far, the largest clinical experience has been limited to percutaneous repair techniques. However, given the complexity and heterogeneity of mitral valve anatomy and pathology, transcatheter mitral valve implantation will widen the mitral valve therapies horizon, toward a patient-tailored approach. Current data about transcatheter mitral valve implantation is still limited and, although some data are promising, there are still some issues to be addressed. This review provides a comprehensive insight into the available devices and describes potential advantages and limitations of transcatheter mitral valve implantation.


The effect of shiftwork on driving to and from work.
A questionnaire study was conducted to obtain information from shiftworkers on the levels of tiredness experienced on the drive to and from work at different times of the day. The results demonstrated that, compared to non-shiftworkers, shiftworkers were more tired on the drive between their home and the workplace and more at risk of falling asleep behind the wheel. The main factors contributing to this increased level of sleepiness and associated driving impairment were the length of the sleep period prior to work, the type of shift and the travelling time. There was some evidence to suggest that on working days shiftworkers were more likely to be involved in an accident than non-shiftworkers. However, there were insufficient data to determine whether accidents were correlated with driver sleepiness.


Melanoma, Viagra, and PDE5 Inhibitors: Proliferation and Metastasis.
Inhibitors of the cGMP-degrading phosphodiesterase (PDE) 5 have achieved blockbuster status in the treatment of penile erectile dysfunction (PED). Their repurposing is currently being proposed to treat certain solid tumours and various other diseases. In cruel irony, however, it appears from recent clinical studies that PDE5 inhibitors may increase the risk of malignant melanoma by negating newly identified brakes on proliferation and metastasis provided by PDE5A.


High variability of genomic instability and gene expression profiling in different HeLa clones.
The HeLa cell line is one of the most popular cell lines in biomedical research, despite its well-known chromosomal instability. We compared the genomic and transcriptomic profiles of 4 different HeLa batches and showed that the gain and loss of genomic material varies widely between batches, drastically affecting basal gene expression. Moreover, different pathways were activated in response to a hypoxic stimulus. Our study emphasizes the large genomic and transcriptomic variability among different batches, to the point that the same experiment performed with different batches can lead to distinct conclusions and irreproducible results. The HeLa cell line is thought to be a unique cell line but it is clear that substantial differences between the primary tumour and the human genome exist and that an indeterminate number of HeLa cell lines may exist, each with a unique genomic profile.


Contesting constructs and interrogating research methods: Re-analysis of qualitative data from a hospital-based case study of self-harm management and prevention practices.
Discourses of self-harm, and also suicide, are often underpinned by a central tenet: prevention is the priority. This belief is seemingly so inscribed in research that it is rarely interrogated. The present paper re-analyses qualitative data from a hospital-based study of self-harm management and prevention practice. It aims to reflect upon, and disrupt, the authors' latent assumptions about the construct of 'prevention', while reflecting on the research method used. Twenty-five individuals participated in semi-structured interviews: healthcare and affiliated professionals (n = 14); parents and carers (n = 8); and children and young people (aged 9-16 years) who had presented to an emergency department for self-harm, with or without suicidal intent (n = 3). We offer two central discursive considerations: (1) Self-harm prevention is largely an unintelligible concept, having to be reflexively constructed in situ. As such, it is questionable whether it makes sense to discuss the prevention of this amorphous and dynamic phenomenon, which cannot always be disentangled from everyday life; (2) Interviews entail significant biographical work for participants, notably the performance of personal and professional competence for the audience. These interactional dynamics offer a glimpse into the priorities, meanings and needs for participants in relation to self-harm. Together these considerations provide useful insights into how the interview method can serve as both a limiting and illuminating site of knowledge creation.


Integrated neural processes for defining potential actions and deciding between them: a computational model.
To successfully accomplish a behavioral goal such as reaching for an object, an animal must solve two related problems: to decide which object to reach and to plan the specific parameters of the movement. Traditionally, these two problems have been viewed as separate, and theories of decision making and motor planning have been developed primarily independently. However, neural data suggests that these processes involve the same brain regions and are performed in an integrated manner. Here, a computational model is described that addresses both the question of how different potential actions are specified and how the brain decides between them. In the model, multiple potential actions are simultaneously represented as continuous regions of activity within populations of cells in frontoparietal cortex. These representations engage in a competition for overt execution that is biased by modulatory influences from prefrontal cortex. The model neural populations exhibit activity patterns that correlate with both the spatial metrics of potential actions and their associated decision variables, in a manner similar to activities in parietal, prefrontal, and premotor cortex. The model therefore suggests an explanation for neural data that have been hard to account for in terms of serial theories that propose that decision making occurs before action planning. In addition to simulating the activity of individual neurons during decision tasks, the model also reproduces key aspects of the spatial and temporal statistics of human choices and makes a number of testable predictions.


Development of an antigen ELISA to detect sapovirus in clinical stool specimens.
Human sapovirus (SaV) strains are etiological agents of mild and/or acute gastroenteritis in children and adults. In this study, we describe the development of a novel antigen enzyme-linked immunosorbent assay (ELISA) detection system that was based on hyperimmune rabbit and guinea pig antisera raised against SaV genogroup I (GI) virus-like particles. The ELISA had 100% specificity, and sensitivities of 60% and 25% when compared to single-round PCR and nested PCR, respectively. Our results have shown the ELISA was useful in detecting SaV GI antigens in clinical stool specimens collected two days after the onset of illness.


The 5-year onset and regression of diabetic retinopathy in Chinese type 2 diabetes patients.
To determine the rate and risk factors of diabetic retinopathy (DR) onset and regression in Chinese type 2 diabetes mellitus patients. This is a 5-year community-based prospective study. The demographic information, systemic examination results and ophthalmological test results of each participant were collected. The study outcomes were DR incidence, defined as the onset of DR in at least one eye, and DR regression, defined as full regression from existing DR to no retinopathy without invasive treatments. The associations between each potential risk factor and the outcomes were studied. In total, 778 participants were enrolled. There were 322 patients without DR at baseline, of which 151 participants developed DR during follow-up (DR incidence rate = 46.89%). Baseline hyperglycemia and high blood pressure were two independent risk factors associated with DR incidence. Among the 456 participants with existing DR at entry, 110 fully recovered after 5 years (DR regression rate = 24.12%). Low baseline glucose and low serum triglyceride were two independent factors associated with DR regression. DR incidence occurred more frequently in patients with hyperglycemia and high blood pressure. DR regression occurred mostly in patients with lower glucose and lower serum triglyceride levels among Chinese type 2 diabetes patients.


Synthesis, Structure, and Luminescence of Mixed-Ligand Lanthanide Trifluoroacetates.
A series of new mixed-ligand lanthanide trifluoroacetates of formula Ln(4-cpno)(tfa)3(H2O)·H2O (Ln = Sm, Eu, Gd, Tb, Dy; 4-cpno = 4-cyanopyridine N-oxide; tfa = trifluoroacetate) is reported. Trifluoroacetates were synthesized as chemically pure polycrystalline solids and their crystal structures were probed using single-crystal and powder X-ray diffraction. Ln(4-cpno)(tfa)3(H2O)·H2O solids make up an isostructural series in which LnO8 polyhedra are bridged by 4-cpno to form edge-sharing dimers. Trifluoroacetato connects these dimers to yield chains whose three-dimensional packing is governed by hydrogen bonds established between 4-cpno, trifluoroacetato, and water. 4-cpno serves as an efficient sensitizer of lanthanide-centered luminescence. UV excitation of its singlet manifold and subsequent energy transfer to the 4f levels of the lanthanides yield orange (Sm), red (Eu), green (Tb), and yellow (Dy) emissions. Sensitization efficiencies reach 81 and 64% for Eu and Tb hybrids, respectively. Tb(4-cpno)(tfa)3(H2O)·H2O displays a quantum yield of 52%, which coupled to the high absorptivity of 4-cpno, makes it a bright-green emitter under 292 nm excitation. Lanthanide trifluoroacetates may therefore serve as hybrid solid-state light emitters provided that adequate sensitizers are identified.