Pancreas-preserving total duodenectomy for advanced duodenal polyposis in patients with familial adenomatous polyposis: short and long-term outcomes.
In patients with familial adenomatous polyposis (FAP), extensive nonmalignant duodenal polyposis not amenable to endoscopic management demands surgical resection for which pancreas-preserving total duodenectomy (PPTD) offers a pancreatic parenchyma sparing approach. This is a retrospective cohort study including consecutive patients who underwent PPTD for FAP. Reconstruction involved a Billroth II anastomosis with a short isolated jejunal limb to facilitate future endoscopic surveillance. Short and long-term outcomes were evaluated. Overall, 30 patients underwent PPTD for Spigelman stage III (n = 6) or IV (n = 24). Sixteen patients experienced a severe complication (Clavien-Dindo grade III/IV) including postoperative pancreatic fistula (ISGPS grade B/C) in twelve. There was no all cause in-hospital and 90-day mortality. During follow-up (median 125 months), five patients developed acute pancreatitis, one new-onset diabetes and one exocrine pancreatic insufficiency. During endoscopic surveillance in 27 patients, jejunal adenomas were detected in 22 and advanced adenomas in 11. An additional surgical resection was required in four patients with extensive jejunal polyposis. None developed jejunal cancer. The 10-year overall survival rate was 93.3%. Postoperative morbidity after PPTD is substantial but on the long-term, rates of pancreatic insufficiencies are low. Most patients develop jejunal adenomas at follow-up, highlighting the need for endoscopic surveillance.


Prostaglandin-induced bicarbonate secretion in the canine stomach: characteristics and evidence for a cholinergic mechanism.
Using a canine chambered stomach preparation, the effect of topical 16,16-dimethyl prostaglandin E2 (dmPGE2) in neutral solution (150 mN NaCl) on gastric mucosal bicarbonate (HCO-3) secretion was assessed. Compared to control studies in which neutral solution alone bathed the epithelium, dmPGE2 (0.5, 1.0, 2.0, and 4.0 micrograms/ml), when applied to gastric mucosa, significantly increased the output of gastric HCO-3 in a stepwise and dose-related fashion. Accompanying these effects in HCO-3 output were similar increases in sodium, potassium, chloride, and gastric perfusate volume. IN other studies, the effects of intravenous atropine and close intraarterial tetrodotoxin on this PG-induced HCO-3 secretion were evaluated. Both agents completely prevented the stimulation of HCO-3 output induced by dmPGE2 (2 micrograms/ml). It is concluded that dmPGE2, when topically applied to canine gastric epithelium, is a potent stimulant of bicarbonate output that is dose-dependent. The ability of atropine and tetrodotoxin to prevent this secretion suggests that a cholinergic mechanism may be involved and that dmPGE2 mediates its effects on HCO-3 output through acetylcholine release which in turn stimulates cholinergic nerve endings.


Rasch Analysis of Social Attitude Barriers and Facilitators to Participation for Individuals with Disabilities.
To develop item banks of social attitude barriers and facilitators to participation and validate them with established instruments. We used the Rasch model to identify misfitting items and rating scale problems, calibrate items, and develop KeyForms and short forms. Correlations between the Social Attitude Barriers and Facilitators item banks with the Patient-Reported Outcomes Measurement Information System (PROMIS) Social Health domain and National Institutes of Health Toolbox Emotional Battery Social Relationships domain were computed to evaluate convergent and divergent validity. Community-dwelling individuals traveled to 3 academic medical centers for testing. Participants (N=558) who had a primary impairment of stroke, spinal cord injury, or traumatic brain injury (mean age, 47.0±16.0y) completed 31 social attitude facilitator and 51 barrier items using a 5-point rating scale. Not applicable. Item banks to measure social attitude barriers and facilitators for individuals with disabilities. After combining the "never" and "rarely" rating scale categories, 30 Facilitator items fit the Rasch model and demonstrated person reliability of 0.93. After collapsing the "never" and "rarely" rating scale categories, 45 Barrier items fit the Rasch model and demonstrated person reliability of 0.95. Ceiling and floor effects were negligible for both item banks. Facilitators and Barriers item banks were negatively correlated, and these banks were moderately correlated with PROMIS and Toolbox measures, providing evidence of convergent and divergent validity. Findings support the reliability and validity of the Social Attitude Facilitators and Barriers item banks. These item banks allow investigators and clinicians to measure perceptions of social attitudes, providing information that can guide individual interventions to reduce barriers and promote facilitators. Moderate correlations between the Social Attitude banks and PROMIS and Toolbox variables provide support for the measurement and theory of environmental influences on social health and participation.


Is RK-682 a promiscuous enzyme inhibitor? Synthesis and in vitro evaluation of protein tyrosine phosphatase inhibition of racemic RK-682 and analogues.
RK-682 (1) is a natural product known to selectively inhibit protein tyrosine phosphatases (PTPases) and is used commercially as a positive control for phosphatase inhibition in in vitro assays. Protein phosphatases are involved in several human diseases including diabetes, cancer and inflammation, and are considered important targets for pharmaceutical development. Here we report the synthesis of racemic RK-682 (rac-1) and a focused set of compounds, including racemic analogues of 1, dihydropyranones and C-acylated Meldrum's acid derivatives, the later obtained in one synthetic step from commercially available starting material. We further characterized the behavior of some representative compounds in aqueous solution and evaluated their in vitro PTPase binding and inhibition. Our data reveal that rac-1 and some derivatives are able to form large aggregates in solution, in which the aggregation capacity is dependent on the acyl side chain size. However, compound aggregation per se is not able to promote PTPase inhibition. Our data disclose a novel family of PTPase inhibitors (C-acylated Meldrum's acid derivatives) and that rac-1 and derivatives with an exposed latent negatively charged substructure (e.g.: the tetronic acid core of 1) can bind to the PTPase binding site, as well promiscuously to protein surfaces. The combined capacity of compounds to bind to proteins together with their intrinsic capacity to aggregate in solution seems essential to promote enzyme aggregation and thus, its inhibition. We also observed that divalent cations, such as magnesium frequently used in enzyme buffer solutions, can deplete the inhibitory activity of rac-1, thus influencing the enzyme inhibition experiment. Overall, these data help to characterize the mechanism of PTPase inhibition by rac-1 and derivatives, revealing that enzyme inhibition is not solely dependent on compound binding to the PTPase catalytic site as generally accepted in the literature. In addition, our results point to promiscuous mechanisms that influence significantly the in vitro evaluation of enzyme inhibition by rac-1. Therefore, we recommend caution when using natural or synthetic RK-682 (1) as an internal control for evaluating PTPase inhibition and selectivity, since many events can modulate the apparent enzyme inhibition.


Accurate assessment of mass, models and resolution by small-angle scattering.
Modern small-angle scattering (SAS) experiments with X-rays or neutrons provide a comprehensive, resolution-limited observation of the thermodynamic state. However, methods for evaluating mass and validating SAS-based models and resolution have been inadequate. Here we define the volume of correlation, Vc, a SAS invariant derived from the scattered intensities that is specific to the structural state of the particle, but independent of concentration and the requirements of a compact, folded particle. We show that Vc defines a ratio, QR, that determines the molecular mass of proteins or RNA ranging from 10 to 1,000 kilodaltons. Furthermore, we propose a statistically robust method for assessing model-data agreements (χ(2)free) akin to cross-validation. Our approach prevents over-fitting of the SAS data and can be used with a newly defined metric, RSAS, for quantitative evaluation of resolution. Together, these metrics (Vc, QR, χ(2)free and RSAS) provide analytical tools for unbiased and accurate macromolecular structural characterizations in solution.


Anti-inflammatory and anti-arthritic effects of Guge Fengtong Formula: in vitro and in vivo studies.
Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major cause of disability. Presently, the clinical therapeutic medicines for inflammatory and arthritic diseases are unsatisfactory due to severe adverse effects or ineffectiveness. The Guge Fengtong formula (GGFT), containing the standardized extracts of Dioscoreae Nipponicae Rhizoma, Spatholobi Caulis, and Zingiberis Rhizoma, has long been used for RA treatment by Chinese doctorsin China. However, the detailed anti-inflammatory and anti-arthritic activity of GGFT has not been reported so far. In the present work, we aimed to evaluate the anti-inflammatory and anti-arthritic effects of GGFT using three in vivo animal models, and tried to uncover its preliminarythe underlying mechanism of action mechanism in RAW 264.7 macrophages. The obtained results indicated that GGFT significantly attenuated ear edema, decreased carrageenan-induced paw edema, reduced the arthritis score, and reversed the weight loss of the complete Freund's adjuvant (CFA)CFA-injected rats. Additionally, marked decrease of in synovial inflammatory infiltration and synovial lining hyperplasia in the joints and decline of inflammatory factors (TNF-α and IL-1β) in the serum were observed in the GGFT-treated rats. In lipopolysaccharide-activated RAW264.7 macrophages, GGFT reduced the production of NO, PGE2, and IL-6, and inhibited the expression of iNOS, COX-2, and NF-κB expression. Our results demonstrated that GGFT possessed considerable anti-inflammatory activity and have had potential therapeutic effects on adjuvant induced arthritis in rats, which provided providing experimental evidences for its traditional application in the treatment of RA and other inflammatory diseases.


Changes in the relative population size of selected ruminal bacteria following an induced episode of acidosis in beef heifers receiving viable and non-viable active dried yeast.
To characterize the changes in the relative population size (RPS) of select ruminal bacteria and rumen fermentation variables in beef heifers supplemented with a strain of Saccharomyces cerevisiae as viable active dried (ADY) or killed dried (KDY) yeast following an induced episode of ruminal acidosis. Six ruminally cannulated beef heifers fed a diet consisting of 50% forage and 50% grain (dry matter basis) were used in a replicated 3 × 3 Latin square design with three 28-day periods. Treatments were: (i) control (CTRL; no yeast); (ii) ADY (4 g day-1 providing 1010 CFU per g; AB Vista, UK); and (iii) KDY (4 g day-1 autoclaved ADY). The acidosis challenge was induced on day 22 and rumen samples were collected on day 15 (baseline; BASE), day 22 (challenge day; CHAL), and on day 29 (168th hour post acid challenge or recovery, REC) of each period. Over the study, duration of pH <5·8 (indicative of subacute ruminal acidosis) was less for ADY and KDY than CTRL, with ADY less than KDY. No treatment effects were observed on relative abundance of ruminal bacteria, but the day effect was significant. The RPS of lactate producers and utilizers was greater while RPS of fibrolytic bacteria was lower during CHAL than BASE and REC. Yeast supplementation, irrespective of its viability, showed beneficial effects on ruminal pH variables in animals more susceptible to acidosis. Rumen microbial population was altered with the induction of severe acidosis. Most of the changes reverted back to baseline values during the recovery phase. Yeast supplementation reduced subacute rumen acidosis in the most susceptible cattle, but failed to attenuate severe acidosis induced by a grain challenge. The study provided valuable insight into the mechanism by which acidosis affects cattle performance. Individual animal variation in ruminal fermentation partly explained the variability in response to yeast supplementation in the study.


Chronic, intermittent convection-enhanced delivery devices.
Intraparenchymal convection-enhanced delivery (CED) of therapeutics directly into the brain has long been endorsed as a medium through which meaningful concentrations of drug can be administered to patients, bypassing the blood brain barrier. The translation of the technology to clinic has been hindered by poor distribution not previously observed in smaller pre-clinical models. In part this was due to the larger volumes of target structures found in humans but principally the poor outcome was linked to reflux (backflow) of infusate proximally along the catheter track. Over the past 10 years, improvements have been made to the technology in the field which has led to a small number of commercially available devices containing reflux inhibiting features. While these devices are currently suitable for acute or short term use, several indications would benefit from longer term repeated, intermittent administration of therapeutics (Parkinson's, Alzheimer's, Amyotrophic lateral sclerosis, Brain tumours such as Glioblastoma Multiforme (GBM) and Diffuse intrinsic Pontine Glioma (DIPG), etc.). Despite the need for a chronically accessible platform for such indications, limited experience exists in this part of the field. At the time of writing no commercially available clinical platform, indicated for chronic, intermittent or continuous delivery to the brain exists. Here we review the improvements that have been made to CED devices over recent years and current state of the art for chronic infusion systems.


A Psychological Profile of the Alt-Right.
The 2016 U.S. presidential election coincided with the rise of the "alternative right," or alt-right. Alt-right associates have wielded considerable influence on the current administration and on social discourse, but the movement's loose organizational structure has led to disparate portrayals of its members' psychology and made it difficult to decipher its aims and reach. To systematically explore the alt-right's psychology, we recruited two U.S. samples: An exploratory sample through Amazon's Mechanical Turk (N = 827, alt-right n = 447) and a larger, nationally representative sample through the National Opinion Research Center's Amerispeak panel (N = 1,283, alt-right n = 71-160, depending on the definition). We estimate that 6% of the U.S. population and 10% of Trump voters identify as alt-right. Alt-right adherents reported a psychological profile more reflective of the desire for group-based dominance than economic anxiety. Although both the alt-right and non-alt-right Trump voters differed substantially from non-alt-right, non-Trump voters, the alt-right and Trump voters were quite similar, differing mainly in the alt-right's especially high enthusiasm for Trump, suspicion of mainstream media, trust in alternative media, and desire for collective action on behalf of Whites. We argue for renewed consideration of overt forms of bias in contemporary intergroup research.


Silver staining of cerebrospinal fluid IgG in isoelectric focusing gels.
A silver staining technique to be used on isoelectric focusing (IEF) gels for cerebrospinal fluid (CSF) oligoclonal IgG bands is described. The technique provides a sensitivity for detection of greater than 0.17 micrograms of IgG. The additional use of immunofixation with anti-human IgG antiserum rather than chemical fixation improves the sensitivity two-fold and permits identification of the oligoclonal bands as IgG. The technique enables one to focus small volumes of unconcentrated CSF (less than 40 microliters) and provides a powerful research tool.


PSRC1 Regulated by DNA Methylation Is a Novel Target for LGG Immunotherapy.
Proline and serine-rich coiled-coil 1 (PSRC1) has been reported to function as an oncogene in several cancers by regulating mitosis, while there are few reports on the role of PSRC1 in lower-grade glioma (LGG). Thus, this study collected 22 samples and 1126 samples from our institution and several databases, respectively, to explore the function of PSRC1 in LGG. First, the analysis of clinical characteristics showed that PSRC1 was always highly expressed in more malignant clinical characteristics of LGG, such as higher WHO grade, recurrence type, and IDH wild type. Second, the prognosis analysis revealed that the high expression of PSRC1 was an independent risk factor contributing to the shorter overall survival of LGG patients. Third, the analysis of DNA methylation showed that the expression of PSRC1 was associated with its 8 DNA methylation sites, overall negatively regulated by its DNA methylation level in LGG. Fourth, the analysis of immune correlation revealed that the expression of PSRC1 was positively correlated with the infiltration of 6 immune cells and the expression of 4 well-known immune checkpoints in LGG, respectively. Finally, co-expression analysis and KEGG analysis showed the 10 genes most related to PSRC1 and the signaling pathways involved by PSRC1 in LGG, respectively, such as MAPK signaling pathway and focal adhesion. In conclusion, this study identified the pathogenic role of PSRC1 in the pathological progression of LGG, expanding the molecular understanding of PSRC1, and provided a biomarker and potential immunotherapeutic target for the treatment of LGG.


A case of refetoff syndrome: selective venous sampling for TSH is useful in differentiating thyroid hormone resistance from TSH secreting tumor.
A 22-year old man with a goiter and clinical manifestations of mild thyrotoxicosis (finger tremor, palpitation, tachycardia) was diagnosed as a syndrome of inappropriate secretion of TSH. Serum concentrations of T4, free T4, T3 and TSH were 24.1 micrograms/100 ml, 4.07 ng/100 ml, 261 ng/100 ml and 1.72 microU/ml, respectively. Thyroidal 131I uptake at 24 hr was 80%. The BMR was within the normal range. He had a normal TSH response to TRH (500 micrograms) with a peak level of 23.8 microU/ml. The basal level of alpha-subunit of TSH was not elevated (0.35 ng/ml). Oral 1-T3 administration (75 and 150 micrograms daily) raised serum T3 concentration, reduced basal TSH and blunted TSH response to TRH. The diurnal variation of TSH was maintained. There was no evidence of abnormalities in the secretion of other pituitary hormones. These findings were compatible with thyroid hormone resistance. However, the presence of a microadenoma in the pituitary gland was suspected with CT scan. Bilateral and simultaneous venous sampling for TSH from inferior petrosal sinus showed no gradient in TSH concentration indicating that a TSH secreting pituitary tumor was unlikely. These data suggest that inappropriate TSH secretion in the present patient is resulted from resistance to thyroid hormone. In the present study selective venous sampling is useful to differentiate the thyroid hormone resistance from a TSH secreting tumor.


Antithrombogenicity of immobilized urokinase and its clinical significance.
Urokinase (UK), a plasminogen activator was immobilized on nylon surface by application of a newly devised technique. When applied clinically, this new preparation proved to have excellent thromboresistance.


[Collagenous gastritis and colitis in a 10-year-old girl].
There are few data in the literature on microscopic gastritis and colitis in the pediatric population. The diagnosis is often made after the occurrence of complications. We report the case of a 10.5 year-old girl for whom the diagnosis was made several years after the initial symptoms. Test for infections, inflammation, and auto-immunity yielded normal results. Upper endoscopy and colonoscopy revealed an abnormal mucosa. However, histology showed microscopic inflammation and fibrotic lesions in the lamina propria, and a thick subepithelial collagenous band. This led to the diagnosis of collagenous gastritis and colitis. Budesonide treatment resulted in the cessation of diarrhea and significant weight gain. Treatment by oral budesonide indeed seems to be highly effective but relapses are frequent when the treatment is stopped. This case shows the importance of being vigilant regarding transit disorders with impact on growth kinetics. Upper endoscopy and colonoscopy need to be carried out when children have organic diarrhea with normal blood tests.


Cloud-Based CT Dose Monitoring using the DICOM-Structured Report: Fully Automated Analysis in Regard to National Diagnostic Reference Levels.
To implement automated CT dose data monitoring using the DICOM-Structured Report (DICOM-SR) in order to monitor dose-related CT data in regard to national diagnostic reference levels (DRLs). We used a novel in-house co-developed software tool based on the DICOM-SR to automatically monitor dose-related data from CT examinations. The DICOM-SR for each CT examination performed between 09/2011 and 03/2015 was automatically anonymized and sent from the CT scanners to a cloud server. Data was automatically analyzed in accordance with body region, patient age and corresponding DRL for volumetric computed tomography dose index (CTDIvol) and dose length product (DLP). Data of 36,523 examinations (131,527 scan series) performed on three different CT scanners and one PET/CT were analyzed. The overall mean CTDIvol and DLP were 51.3% and 52.8% of the national DRLs, respectively. CTDIvol and DLP reached 43.8% and 43.1% for abdominal CT (n=10,590), 66.6% and 69.6% for cranial CT (n=16,098) and 37.8% and 44.0% for chest CT (n=10,387) of the compared national DRLs, respectively. Overall, the CTDIvol exceeded national DRLs in 1.9% of the examinations, while the DLP exceeded national DRLs in 2.9% of the examinations. Between different CT protocols of the same body region, radiation exposure varied up to 50% of the DRLs. The implemented cloud-based CT dose monitoring based on the DICOM-SR enables automated benchmarking in regard to national DRLs. Overall the local dose exposure from CT reached approximately 50% of these DRLs indicating that DRL actualization as well as protocol-specific DRLs are desirable. The cloud-based approach enables multi-center dose monitoring and offers great potential to further optimize radiation exposure in radiological departments. • The newly developed software based on the DICOM-Structured Report enables large-scale cloud-based CT dose monitoring • The implemented software solution enables automated benchmarking in regard to national DRLs • The local radiation exposure from CT reached approximately 50 % of the national DRLs • The cloud-based approach offers great potential for multi-center dose analysis.


Nurses' experience of integrating evidence-based changes into their practice: A qualitative study.
To explore the experiences of neonatal and NICU nurses on participating in evidence-based changes in their neonatal pain management practice. It is a qualitative conventional content analysis. A purposive sample with nurses working in neonatal and NICUs was used. The data were collected through 11 semi-structured in-depth individual interviews, five focused group discussions, and observations and analyzed using the conventional content analysis method based on the Elo and Kyngäs model. The COREQ checklist was used for writing the report. Analysis of gathered data led to the emergence of four themes, including 'being in a supportive and encouraging atmosphere', 'a journey from resistance to adherence', 'achieving multi-dimensional improvements', and 'facing obstructive challenges'.


FleQ regulates both the type VI secretion system and flagella in Pseudomonas putida.
Based on the analysis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry, flagellin FliC and a key member of the type VI secretion system Hcp1 were found to be secreted from Pseudomonas putida KT2442 cells in the late exponential phase, but in the early exponential phase only FliC was secreted. Relevant genes fleQ and rpoN were then individually deleted in P. putida KT2442, and the expression and transcription of fliC and hcp1 in these mutant strains were analyzed. In both △fleQ and △rpoN mutant cells, Hcp1 but not FliC was secreted in the late exponential phase, and it was secreted even in the early exponential phase. Transcriptomic analysis of △fleQ cells shows that most of the genes relevant to the type VI secretion system, including hcp1, were upregulated; several genes involved in 3',5'-cyclic diguanylic acid (c-di-GMP) synthesis and degradation were also significantly regulated. To further study the regulation process of the type VI secretion system, the phosphodiesterase BifA was overexpressed to lower the intracellular c-di-GMP level. The results demonstrate that FleQ positively regulates flagella biosynthesis but negatively regulates the type VI secretion system in P. putida. This finding is important for understanding the function and regulation of the type VI secretion system.


Structural basis of family-wide Rab GTPase recognition by rabenosyn-5.
Rab GTPases regulate all stages of membrane trafficking, including vesicle budding, cargo sorting, transport, tethering and fusion. In the inactive (GDP-bound) conformation, accessory factors facilitate the targeting of Rab GTPases to intracellular compartments. After nucleotide exchange to the active (GTP-bound) conformation, Rab GTPases interact with functionally diverse effectors including lipid kinases, motor proteins and tethering complexes. How effectors distinguish between homologous Rab GTPases represents an unresolved problem with respect to the specificity of vesicular trafficking. Using a structural proteomic approach, we have determined the specificity and structural basis underlying the interaction of the multivalent effector rabenosyn-5 with the Rab family. The results demonstrate that even the structurally similar effector domains in rabenosyn-5 can achieve highly selective recognition of distinct subsets of Rab GTPases exclusively through interactions with the switch and interswitch regions. The observed specificity is determined at a family-wide level by structural diversity in the active conformation, which governs the spatial disposition of critical conserved recognition determinants, and by a small number of both positive and negative sequence determinants that allow further discrimination between Rab GTPases with similar switch conformations.


Growing Up in a Changing World: Environmental Regulation of Development in Insects.
All organisms are exposed to changes in their environment throughout their life cycle. When confronted with these changes, they adjust their development and physiology to ensure that they can produce the functional structures necessary for survival and reproduction. While some traits are remarkably invariant, or robust, across environmental conditions, others show high degrees of variation, known as plasticity. Generally, developmental processes that establish cell identity are thought to be robust to environmental perturbation, while those relating to body and organ growth show greater degrees of plasticity. However, examples of plastic patterning and robust organ growth demonstrate that this is not a hard-and-fast rule.In this review, we explore how the developmental context and the gene regulatory mechanisms underlying trait formation determine the impacts of the environment on development in insects. Furthermore, we outline future issues that need to be resolved to understand how the structure of signaling networks defines whether a trait displays plasticity or robustness.


Non-cultured epidermal cells suspended in either platelet-rich plasma or ringer lactate for stable vitiligo: A prospective comparative study.
Noncultured epidermal cell suspension (NCES) transplantation is a commonly used surgical treatment for resistant stable vitiligo. The combination of platelet-rich plasma (PRP) with different therapeutic modalities for vitiligo yielded higher repigmentation response, probably due to platelet-derived growth factors. To evaluate the efficacy of PRP-suspended NCES compared to NCES suspended in Ringer's lactate (RL) solution in the treatment of stable vitiligo. A prospective comparative study was conducted on 40 patients with stable vitiligo. They were divided into two equal groups: group A (treated with RL-suspended NCES) and group B (treated with PRP-suspended NCES). All patients were followed-up for 6 months for assessment of their therapeutic response regarding clinical outcomes and immunohistochemical expression of HMB-45 in lesional skin. Patients treated with PRP-suspended NCES showed a significantly higher repigmentation response compared to those treated with RL-suspended NCES at 1, 3, and 6 months after treatment (p = 0.015, 0.023, 0.029, respectively). The expression of HMB-45 significantly increased in both groups after therapy, but without a significant difference between the two groups. The repigmentation response of NCES can be enhanced by suspending the melanocytes in autologous PRP.


Gait analysis of anterior cruciate ligament reconstructed subjects with a combined tendon obtained from hamstring and peroneus longus.
Stability of the knee joint is achieved by a complex process in which the anterior cruciate ligament (ACL) plays an important role. The rupture of this ligament is quite frequent especially in athletic young subjects. Various methods have been used to reconstruct the ACL. One of the new methods is to use a graft combined from peroneus longus and hamstring. As there is no evidence regarding this method, it was aimed to evaluate the efficiency of this method. Two groups of normal and those with ACL injury, in whom their ACLs were reconstructed with the new method, participated in this study. The kinematic and kinetic parameters during walking on level surface were evaluated by a motion analysis system (Qualysis) and a Kistler force plate. The difference between the parameters of operated and non-operated sides and also between patients and normal subjects was evaluated by use of a two sample t test (p-value was 0.05). The results of this study showed that the pattern and magnitude of the loads transmitted by lower extrimity joints differed between normal and ACL reconstructed subjects. The sound side pattern and magnitude of motion were also influenced by ACL insufficiency. The results of the current study showed that the reconstructed ACL by use of this method did not have enough performance to restore the function of the leg. As the knee joint is unstable following the use of this method, it is recommended to find a new method of ACL reconstruction to improve the function of this ligament after reconstruction.


Health advocacy: bringing clarity to educators through the voices of physician health advocates.
Although advocacy is a value that is acknowledged among care providers, the definition of advocacy and the competencies associated with it vary among those who teach it. Grounded theory analysis was used on case studies of eight physicians identified as being responsive to community needs. Community-responsive physicians were found to engage in health advocacy by working with, or on behalf of, their patients/communities through being either (a) informants-providing information to those who can enact change, or (b) change agents-initiating, mobilizing, and organizing ways to systematically modify policies or procedures that negatively effect patients/communities. Issues of health advocacy as they relate to the determinants of health and health promotion are highlighted. This article provides an enhanced understanding of health advocacy and proposes an operational definition of health advocacy that may allow for an enhanced method of teaching health advocacy to learners.


Healthcare Costs at the End of Life for Patients with Non-cancer Diseases and Cancer in Denmark.
To examine costs of care from a healthcare sector perspective within 1 year before death in patients with non-cancer diseases and patients with cancer. This nationwide registry-based study identified all Danish citizens dying from major non-cancer diseases or cancer in 2010-2016. Applying the cost-of-illness method, we included costs of somatic hospitals, including hospital-based specialist palliative care, primary care, prescription medicine and hospice expressed in 2022 euros. Costs of patients with non-cancer diseases and cancer were compared using regression analyses adjusting for sex, age, comorbidity, residential region, marital/cohabitation status and income level. Within 1 year before death, mean total healthcare costs were €27,185 [95% confidence interval (CI) €26,970-27,401] per patient with non-cancer disease (n = 109,723) and €51,348 (95% CI €51,098-51,597) per patient with cancer (n = 108,889). The adjusted relative total healthcare costs, i.e. the ratio of the mean costs, of patients with non-cancer diseases was 0.64 (95% CI 0.63-0.66) at 12 months before death and 0.91 (95% CI 0.90-0.92) within 30 days before death compared with patients with cancer. Mean costs of hospital-based specialist palliative care and hospice in the year leading up to death were €17 (95% CI €13-20) and €90 (95% CI €77-102) per patient with non-cancer disease but €1552 (95% CI €1506-1598) and €3411 (95% CI €3342-3480) per patient with cancer. Within 1 year before death, total healthcare costs, mainly driven by hospital costs, were substantially lower for patients with non-cancer diseases compared with patients with cancer. Moreover, the costs of hospital-based specialist palliative care and hospice were minimal for patients with non-cancer diseases.


Using SERS-based microfluidic paper-based device (μPAD) for calibration-free quantitative measurement of AMI cardiac biomarkers.
Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based μPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based μPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based μPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.


The European Union Current Asylum Policy: Selected Problems in the Shadow of COVID-19.
Recent years in Europe have generated situations requiring the European Union to take extra-coordinated action in the field of asylum policy. The sudden and growing influx of refugees to Europe in 2015 and 2016 has caused the collapse of the previous common European asylum system. The European Union has taken a number of measures to resolve this crisis situation. When the situation seemed to be under control, a new challenge emerged in early 2020. The first COVID-19 infectious disease case was reported in Europe, and on 13 March 2020 the WHO reported that Europe had become the epicentre of the coronavirus pandemic. The measures taken by individual countries and the European Union to limit the spread of the virus have had a significant impact on many spheres of state and individual functioning, including the situation of persons seeking international protection. This publication consists of three parts. The first part discusses actions taken by the European Union in the face of the migration and refugee crisis that emerged in 2015 and 2016. The second part presents one of the limitations introduced in connection with preventing the spread of COVID-19, which has a huge impact on persons wishing to seek international protection, i.e., changes in the regime of crossing borders and entering the territory of particular countries. The third one points out selected problems experienced by persons seeking protection who already stay in the territory of EU Member States.


Ion-pair extraction of bile acids with Lipidex gel.
A new method for the extraction of bile acids from aqueous solutions, urine, plasma, and bile is described. A buffered solution of decyltrimethylammonium bromide is added to the sample to give a 0.03 M concentration of the counter-ion. The mixture is passed through a bed of Lipidex 1000, which is then washed with the buffered solution of counter-ion followed by water. The decyltrimethylammonium salts of bile acids are sorbed by the Lipidex and are eluted with methanol. Recoveries of unconjugated, taurine- and glycine-conjugated, sulfated, and glucuronidated bile acids are close to 100%. Unconjugated bile acids can also be quantitatively extracted from aqueous solutions and urine after acidification with acetic acid.


Signal transduction by protein kinase C in mammalian cells.
1. The past two decades have witnessed great advances in our understanding of the role of protein kinase C (PKC) in signal transduction. The Ca(2+)-activated, phospholipid-dependent protein kinase discovered by Nishizuka's group in 1977 is now a family of at least 11 isoforms. Protein kinase C isoforms exist in different proportions in a host of mammalian cells and each isoform has a characteristic subcellular distribution in each cell type. 2. Stimulation of a specific PKC isoform often causes redistribution of the isoform from one subcellular compartment to another compartments where it complexes with and phosphorylates a specific protein substrate. 3. The interaction of a specific PKC isoform with its protein substrate may directly activate a specific function of the cell or may trigger a cascade of protein kinases that ultimately stimulates a specific response in differentiated cells or regulates growth and proliferation in undifferentiated cells.


Drought sensitivity of three co-occurring conifers within a dry inner Alpine environment.
We applied dendroclimatological techniques to determine long-term stationarity of climate-growth relationships and recent growth trends of three widespread coniferous tree species of the central Austrian Alps, which grow intermixed at dry-mesic sites within a dry inner Alpine environment (750 m asl). Time series of annual increments were developed from > 120 mature trees of Picea abies, Larix decidua and Pinus sylvestris. Calculation of response functions for the period 1911 - 2009 revealed significant differences among species in response to climate variables. While precipitation in May - June favoured radial growth of Picea abies and Larix decidua, Pinus sylvestris growth mainly depended on April - May precipitation. P. abies growth was most sensitive to May - June temperature (inverse relationship). Moving response function coefficients indicated increasing drought sensitivity of all species in recent decades, which is related to a decline in soil moisture availability due to increasing stand density and tree size and higher evapotranspiration rates in a warmer climate. While recent trend in basal area increment (BAI) of L. decidua distinctly declined implying high vulnerability to drought stress, moderately shade-tolerant P. abies showed steadily increasing BAI and quite constant BAI was maintained in drought adapted P. sylvestris, although at lowest level of all species. We conclude that synergistic effects of stand dynamics and climate warming increased drought sensitivity, which changed competitive strength of co-occurring conifers due to differences in inherent adaptive capacity.


Frontrunners of T cell activation: Initial, localized Ca2+ signals mediated by NAADP and the type 1 ryanodine receptor.
The activation of T cells is the fundamental on switch for the adaptive immune system. Ca(2+) signaling is essential for T cell activation and starts as initial, short-lived, localized Ca(2+) signals. The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) forms rapidly upon T cell activation and stimulates early Ca(2+) signaling. We developed a high-resolution imaging technique using multiple fluorescent Ca(2+) indicator dyes to characterize these early signaling events and investigate the channels involved in NAADP-dependent Ca(2+) signals. In the first seconds of activation of either primary murine T cells or human Jurkat cells with beads coated with an antibody against CD3, we detected Ca(2+) signals with diameters close to the limit of detection and that were close to the activation site at the plasma membrane. In Jurkat cells in which the ryanodine receptor (RyR) was knocked down or in primary T cells from RyR1(-/-) mice, either these early Ca(2+) signals were not detected or the number of signals was markedly reduced. Local Ca(2+) signals observed within 20 ms upon microinjection of Jurkat cells with NAADP were also sensitive to RyR knockdown. In contrast, TRPM2 (transient receptor potential channel, subtype melastatin 2), a potential NAADP target channel, was not required for the formation of initial Ca(2+) signals in primary T cells. Thus, through our high-resolution imaging method, we characterized early Ca(2+) release events in T cells and obtained evidence for the involvement of RyR and NAADP in such signals.


Pre-conditioning with tanshinone IIA attenuates the ischemia/reperfusion injury caused by liver grafts via regulation of HMGB1 in rat Kupffer cells.
We have evaluated the protective mechanism of tanshinone IIA in ischemia/reperfusion injury (IRI) induced by liver grafts, revealing novel supplementary immunotherapy for liver transplantation. The tanshinone IIA preconditioning group (TP group) was pretreated with tanshinone IIA via intraperitoneal injection for 1 week before receiving orthotopic liver transplantation with hepatic arterial ischemia for 30min. The sham-operation group (SO group), control graft group (CG group) and IRI group were pretreated with an equivalent volume of normal saline. The IRI group and CG group received orthotopic liver transplantation with or without hepatic arterial ischemia. Rats were sacrificed at each time point, serum was collected for ELISA detection, and Kupffer cells (KCs) were isolated to extract total protein and RNA for western blotting and real-time PCR, respectively. The levels of TNF-α and IL-4 in the TP group were significantly lower than those of in the IRI group; meanwhile the IL-10 and TGF-β levels were significantly higher than in the IRI group. The protein and mRNA expression levels of HMGB1 were significantly lower in TP group than in the IRI group at each time point. The TLR-4, Myd88, NLRP3 and p-NF-κb p65 expression levels in the TP groups were significantly lower than those in the IRI group, while the PTEN, PI3K and AKT phosphorylation levels in the TP groups were significantly higher than those in the IRI group. Tanshinone IIA attenuates IRI caused by liver grafts via down-regulation of the HMGB1-TLR-4/NF-κb pathway in KCs and activation of PTEN/PI3K/AKT pathway, suggesting a potential role for prevention of liver cell IRI during liver transplantation.


A very small viral double-stranded RNA.
UmV is a double-stranded RNA (dsRNA) virus of the corn fungal pathogen Ustilago maydis. UmV has no infectious cycle. Some UmV subtypes have viral dsRNAs encoding secreted toxins that kill sensitive cells of the same species and related species. There are three viral subtypes, P1, P4 and P6, which differ in the specificity of their secreted killer toxins. Each has three size classes of dsRNA: H (heavy), M (medium) and L (light). The L segments of UmV are unique in being derived from one end of the larger M segments. We have sequenced P1 L and placed it at the 3' end of the P1 M1 plus strand. In their overlapping regions, these dsRNAs are identical in sequence. In vitro translation of P1 M1 results in a peptide whose size is consistent with its being encoded by the non-L region of M1. P1 L is a very small dsRNA of 355 bp. It has no long open reading frames and produces no detectable in vitro translation product. The sequence of P1 L suggests that it is derived by a process unique among dsRNA viruses: replication and packaging of the 3' end fragment of a processed mRNA.


Robotic hysterectomy using the Vessel Sealer for myomatous uteri: technique and clinical outcome.
Robotic procedures using the Vessel Sealer are not well reported in the literature, especially given the advantages of sealing devices already studied in standard laparoscopic procedures. This study reports our experience with the EndoWrist(®) One™ Vessel Sealer in robotic hysterectomy for myomatous uteri. In this retrospective cohort study of the first 50 consecutive patients with myomatous uteri undergoing a robotic hysterectomy, we report our experience with the EndoWrist(®) One™ Vessel Sealer (Intuitive Surgical Inc., Sunnyvale, CA) during this procedure. The learning curve was evaluated, and the operative times as well as the complications were recorded. After the first 10 cases, the median console and total (skin-to-skin) operative time dropped significantly from 110 to 60min and from 158 to 105min, respectively (p=0.018 and p=0.008 respectively). The body mass index (≤ or >30kg/m(2)), uterine weight (≤ or >250g), and uterine size had no statistical significant effect on the total operative time. Median blood loss during surgery was 63mL in all cases (range: 0-400mL). The morbidity was low, and approximately 50% of cases could be discharged from the hospital after one to two days. Robotic hysterectomy using the Vessel Sealer has, after a short learning curve of 10 cases, similar operative times than other published reports on robotic hysterectomy or laparoscopic hysterectomy using a sealing device for myomatous or large uteri.


The effect of an interventional program on the occurrence of medication errors in children.
Medication errors in hospitalized children represent a serious health problem; these include dosing errors, administration route errors, errors in identifying the patient and more. The rates of medication errors are considered higher in children compared to adults because, among other reasons, the pediatric dose is calculated according to the child's weight or body surface. This study aims to examine the incidence of pediatric medication dosing errors and the impact of an intervention program in reducing these errors and related adverse effects in a cohort of hospitalized children at an otolaryngology department. We reviewed 100 computerized medical reports of hospitalized children from 2017 to 2018, including 50 inpatient admissions prior to the implementation of an intervention program and 50 inpatient admissions following its implementation. Data includes demographic variables, number of hospitalization days, rates and types of medication errors and adverse effects. We have analyzed the rates of medication errors before and after implementation of an interventional program. The average patient age was 5.26 and the demographic features of the two groups were similar. We identified 23.2% medication dosing errors in medications prescribed to the patients (n = 33) and 17.6% medication dosing errors in total medications administered to the patients (n = 64) in the pre-intervention group (PREG). In the post-intervention group (POSG) we identified 10.6% medication dosing errors in prescriptions prescribed to the patients (n = 12) and 7% medication dosing errors in the total drugs administered to the patients (n = 21). The intervention program resulted in 46% reduction of prescription errors; No adverse effects were recorded. Medication dosing errors among hospitalized children are common, although rates of adverse events are low. The suggested intervention program demonstrates a significant reduction in the rates of these errors, thus improving the safety of hospitalized children.


Electrodermal and vascular orienting response in schizophrenic patients: relationship to symptoms and medication.
Peripheral indicators of autonomic nervous system activity, including electrodermal activity and finger-pulse volume, were investigated in 100 schizophrenic inpatients. Healthy siblings of the patients and healthy subjects matched for age and gender served as control groups. Acoustic stimuli (70 dB) were presented and orienting response (OR) parameters were determined independently for the two response systems. The relationship of both OR measures to negative symptoms and medication was studied. The two OR measures were found to be not interrelated, i.e. most of the subjects were discordant with regard to presence or absence of their OR in the two different response systems. The electrodermal, but not the vascular OR, differed between patients and control groups. Among patients receiving medication with anticholinergic effects there were significantly more electrodermal nonresponders than among patients without such medication. There was no indication that electrodermal nonresponders show more negative symptoms or generally more severe psychopathology than electrodermal responders.


Development of the aza-crown ether metal complexes as artificial hydrolase.
Hydrolases play a crucial role in the biochemical process, which can catalyze the hydrolysis of various compounds like carboxylic esters, phosphoesters, amides, nucleic acids, peptides, and so on. The design of artificial hydrolases has attracted extensive attention due to their scientific significance and potential applications in the field of gene medicine and molecular biology. Numerous macrocyclic metal complexes have been used as artificial hydrolase in the catalytic hydrolysis of the organic substrate. Aza-crown ether for this comment is a special class of the macrocyclic ligand containing both the nitrogen atoms and oxygen atoms in the ring. The studies showed that the aza-crown complexes exhibited high activity of hydrolytic enzyme. However, the aza-crown ether metal complex as artificial hydrolase is still very limited because of its difficulty in synthesis. This review summarizes the development of the aza-crown ether metal complexes as the artificial hydrolase, including the synthesis and catalysis of the transition metal complexes and lanthanide metal complexes of aza-crown ethers. The purpose of this review is to highlight: (1) the relationship between the structure and hydrolytic activity of synthetic hydrolase; (2) the synergistic effect of metal sites and ligands in the course of organic compound hydrolysis; and (3) the design strategies of the aza-crown ethers as hydrolase.


Comparative mapping of mouse chromosome 2 and human chromosome 9q: the genes for gelsolin and dopamine beta-hydroxylase map to mouse chromosome 2.
The mapping of human chromosome 9 (HSA9) and mouse chromosome 2 (MMU2) has revealed a conserved syntenic region between the distal end of the long arm of chromosome 9 and proximal mouse chromosome 2. Two genes that map to human chromosome 9q34, gelsolin (GSN) and dopamine beta-hydroxylase (DBH), have not previously been located in the mouse. We have used an interspecific backcross to map each of these genes, by Southern blot analysis, to mouse chromosome 2. Gelsolin (Gsn) is tightly linked to the gene for complement component C5 (Hc), and dopamine beta-hydroxylase (Dbh) is just proximal to the Abelson leukemia virus oncogene (Abl) and alpha-spectrin 2 (Spna-2). The loci for gelsolin and dopamine beta-hydroxylase therefore form part of the conserved synteny between HSA9q and MMU2.


A sandwich ELISA based on anti-apo(a) and anti-apo B monoclonal antibodies for lipoprotein(a) measurement.
Lipoprotein(a) (Lp(a)) is one of the most important independent risk factors for the prediction of premature atherosclerosis. Lp(a) is a low-density lipoprotein (LDL)-like particle which contains a glycoprotein (apoprotein(a)) disulfide linked to apo B-100. We describe a sandwich ELISA based on an anti-apo(a) monoclonal antibody (MAb) and an anti-apo B MAb for the quantitative determination of Lp(a) in human serum. The assay is sensitive, precise and specific. Samples with different apo(a) isoforms had a linear response in a range of 3-70 mg/dl of Lp(a). Correlations between the ELISA and a commercial ELISA, an immunoradiometric assay and electroimmunodiffusion were 0.92, 0.96 and 0.98, respectively. The frequency distribution of Lp(a) concentration in blood donors showed the skew toward the right reported in other populations. Patients with angiographically assessed coronary atherosclerosis had three times higher levels of Lp(a) than those with no signs of coronary atherosclerosis.


Prominent ears--Pitanguy's island technique: long-term results.
Through the analysis of 300 cases of prominent ears operated by Pitanguy's technique with a follow-up of 1-15 years we observed the preservation of the aesthetic aspect as well as the cephaloauricular angle. We call attention to its easy performance and almost no incidence of early or late complications.


Plasminogen activator activity in the porcine oviduct during the oestrous cycle.
The mammalian oviduct is a dynamic tissue, which lies under the influence of ovarian steroids and produces proteins that affect various stages of fertilization and post-fertilization events. In this study, expression of urokinase-type plasminogen activator (u-PA mRNA) and plasminogen activator activity (PAA) were examined in porcine oviducts by reverse transcription and polymerase chain reaction (RT-PCR) and activity assays, respectively. For this purpose, oviducts were collected from Landrace cycling sows and divided into three segments (isthmus, ampulla, infundibulum). Different concentrations of u-PA mRNA were detected in the three segments following the pattern isthmus>ampulla>infundibulum and this pattern was maintained during the oestrous cycle. On the contrary, the highest PAA was measured in the ampulla compared to the isthmus and the infundibulum and the highest ampullary PAA was detected during the first 2 days of the oestrous cycle. The different regulation of u-PA mRNA expression and PAA is probably due to the existence of PA inhibitors. Recent observations suggest that PAI-1, the main inhibitor of PAs, shows greater expression in the isthmus compared to the ampulla and the local generation of plasmin is inhibited. The latter may be related to observations that spermatozoa are quiescent in the isthmus before fertilization. This study supports the suggestion that urokinase-type plasminogen activator has a biological role within the porcine oviduct, especially at or near the time of fertilization.


Quality of life and disease severity in patients with atopic dermatitis.
Atopic dermatitis (AD) affects quality of life (QoL) negatively in patients and their families. We examined the relationship between disease severity and QoL in patients with AD. Consecutive, newly referred outpatients with AD, 4 years of age or older, were assessed from January 2012 onwards by means of the dermatology life quality index (DLQI, range 0-30), the Scoring of AD (SCORAD) disease severity score (range 0-103), filaggrin gene (FLG) mutation status and paraclinical tests related to allergy. A total of 250 patients with a mean age of 26.0 years were identified with complete data on DLQI; 148 (59.2%) females and 102 (40.8%) males. Of these 45.6% had asthma, 46.8% had hay fever, 22.7% had a loss-of-function mutation in FLG, and 61.9% had one or more inhalant allergic sensitizations. The correlation between SCORAD and DLQI was 0.42 (P < 0.001). After multivariate adjustment there was an increasing mean DLQI score with increasing disease severity measured by SCORAD (DLQI in mild = 5.30, moderate = 8.59 and severe = 11.94 AD), P-value for difference between groups <0.001; a higher mean DLQI among females than males (9.73 vs. 8.34), P = 0.028; and among patients reporting facial eczema (9.88 vs. 6.24), P = 0.012. No statistically significant influence on DLQI was found for hand or foot eczema, age, blood eosinophil count, allergic sensitization, asthma, hay fever, FLG mutation status and smoking. FLG null mutation status was not significantly associated with SCORAD. AD impacts negatively on the QoL, proportional to the severity of the disease. Furthermore, female sex and facial eczema are associated with low QoL. Positive FLG null mutation status is not associated with QoL or disease severity.


Effect of contrast on the perception of moving multiple Gabor patterns.
The present study examined the way in which the perception of motion coherency depends on luminance contrast. Pseudo-plaid patterns were presented to subjects who judged whether coherent motion or component motion of the Gabor patterns was perceived. Michelson contrast, eccentricity, spatial separation, and angular separation between two groups of Gabor patches were varied systematically. When the contrast was high, coherent motion perception was dominant in peripheral viewing but not in foveal viewing. When the contrast was low, coherent motion was perceived at all eccentricities. Under low-contrast conditions and with peripheral viewing, coherent motion was perceived over broader spatial areas and at wider angular separations. The contrast dependency of motion coherency can be qualitatively explained in terms of the relative activity of hypothetical local-motion units in area V1 and global-motion units in area MT of the visual cortex.


Early growth response-1 mediates downregulation of telomerase in cervical cancer.
Early growth response (Egr)-1 is a transcription factor that triggers transcription of downstream genes within 15-30 min of various stimulations. These genes are expressed rapidly through specific promoter activation and mediate cell growth and angiogenesis. Following the previous computational identification of a site that was thought to be an Egr-1 consensus binding site at -273 to -281 in the human telomerase reverse transcriptase (hTERT) promoter region, the present study was conducted to evaluate the role of Egr-1 in the regulation of hTERT and telomerase in uterine cervical cancer. First, the expression of Egr-1 and hTERT at the mRNA level was examined in cervical cancer tissues. Egr-1 and hTERT were expressed much higher in cervical cancer tissues than in the normal cervix. However, a negative correlation was noted in the expression between Egr-1 and hTERT. By luciferase assay using hTERT promoter constructs, hTERT transcriptional activation was shown to be inhibited when Egr-1 was overexpressed. Furthermore, Egr-1 overexpression decreased hTERT protein production as well as hTERT mRNA as observed by western blotting analysis and real-time reverse transcription-polymerase chain reaction, respectively. The present study suggests that Egr-1 plays an important regulatory role in the transcriptional activation of hTERT.


Improvement of renal preservation by verapamil with 24-hour cold perfusion in the isolated rat kidney.
There is substantial evidence that increased cellular calcium may activate processes that lead to cellular injury and death, and calcium entry blockers (CEB) have been shown to protect against renal ischemic injury. This approach has been used experimentally to enhance kidney preservation during both warm and cold ischemia. In the present study, the effect of the CEB verapamil on kidney function after 24 hr of hypothermic (4-7 degrees C) perfusion was examined and compared with simple cold storage with Eurocollins' solution (4 hr), 4 or 24 hr cold perfusion, without the addition of verapamil. The cold perfusion media consisted of 3% albumin in phosphate-free Krebs-Henseleit saline supplemented with 5 mM glucose. Cold perfusion was performed at 40 mmHg perfusion pressure with either 0 (C) or 5 microM verapamil (V) added to the cold perfusion media. Renal functional parameters of plasma flow (RPF), inulin clearance (Cin), fractional (FRNa+) and net sodium reabsorption (TNa+) were assessed during 60 min of reperfusion at 37 degrees C using 6.7% albumin in Krebs-Henseleit saline supplemented with glucose, inulin, and 20 amino acids. There was no increase in RPF with V (33 +/- 1 vs. 32 +/- 2 ml/min/g,NS) but Cin was significantly higher (271 +/- 30 vs. 168 +/- 20 microliter/min/g P less than 0.01) with V. Preservation of tubular function by V was demonstrated by an increase in FRNa+ (84 +/- 5 vs. 57 +/- 8%, P less than .01), TNa+ (32 +/- 6 vs. 15 +/- 3 mumol/min/g, P less than .01) and renal adenosine triphosphate (ATP) concentration (8.0 +/- 5 vs. 4.7 +/- 1.0 mumol/g dry tissue, P less than .01). Thus, V appears not only to enhance kidney preservation with warm and cold ischemia but also improves renal function, as assessed by glomerular filtration rate (GFR) tubular function, and tissue ATP concentration with 24-hr cold perfusion.


Quantitation and distribution analysis of glial fibrillary acidic protein in human glioma cells in culture.
The amount and distribution of glial fibrillary acidic protein (GFAP) were determined by flow cytometry (FCM) and an enzyme-linked immunosorbent assay (ELISA) in five human glioma cell lines stained by the indirect immunofluorescence method using anti-GFAP monoclonal antibody. Standard reference beads containing a known amount of fluorescein were used to calibrate the flow cytometer; however, the intensity of fluorescence from these beads was too weak to allow direct comparison with the fluorescence from the stained cells. Therefore, the flow cytometer was recalibrated using reference beads with a fluorescence intensity similar to that of the glioma cells. By comparing the fluorescence intensities of the two types of reference beads, it was possible to determine the fluorescein content of the stained cells directly from the relative fluorescence intensity (channel number). Glioma cell lines 343 MGA, SF 126, SF 188, U 251, and U 87 had fluorescein concentrations of 72.0 +/- 6.8, 8.1 +/- 0.3, 52.6 +/- 3.1, 86.4 +/- 4.0, and 56.2 +/- 2.9 x 10(5) (mean +/- standard error) Eq Sol Mol (equivalent solution of mole), respectively. The GFAP content of these cell lines, determined by ELISA, was 15.7 +/- 5.2, 0.5 +/- 0.1, 11.1 +/- 2.0, 20.8 +/- 4.6, and 9.5 +/- 2.7 pg GFAP/cell, respectively, and correlated closely with the results of FCM (R = 0.983, p less than 0.0028). A linear regression analysis yielded the following equation: pg GFAP/cell = -2.3376 + 0.2518 x FCM integrated mean channel number (fluorescein concentration: 10(5) Eq Sol Mol).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of substance P on Na and K transport in perfused main submandibular duct of rat.
Substance P (2 and 4 micrograms/kg . min, iv) caused an inhibition of net efflux of Na and net influx of K in perfused main excretory duct of rat submandibular gland. These effects could not be blocked by atropine sulfate. The data suggest that substance P receptors are present in the duct cells and play a role in the regulation of transductal electrolyte transport.


Mould and mycotoxin contamination of pig feed in northwest Croatia.
The aim of this study was to investigate the contamination of pig feed with moulds and the occurrence of mycotoxins. A total of 30 feed samples were collected at different animal feed factories in the north-western part of Croatia. Mycological analysis showed that the total number of moulds ranged from 1 × 10(3) to 1 × 10(5) cfu/g with samples contaminated with Aspergillus spp. (63 %), Penicillium spp. (80 %), and Fusarium spp. (77 %). A determination of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEA), deoxynivalenol (DON), T-2 toxin (T-2) and fumonisin (FUM) concentration was done using the validated ELISA method. The mean concentrations of AFB1 (0.5 ± 0.6 μg/kg), OTA (1.53 ± 0.42 μg/kg) and FUM (405 ± 298 μg/kg) were below the maximum levels or recommended values in the EU in all the investigated samples. The observed results indicated an increased contamination of pig feed with Fusarium mycotoxins DON and ZEA with mean concentrations of 817 ± 447 and 184 ± 214 μg/kg, higher than recommended in 40 and 17 % of the analysed samples, respectively.


Metabolomic analysis reveals dose-dependent alteration of maize (Zea mays L.) metabolites and mineral nutrient profiles upon exposure to zerovalent iron nanoparticles.
Nanoscale zero-valent iron (nZVI) has been widely applied in the environmental field to degrade organic pollutants. The potential risk posed from nZVI on crop species is not well understood and is critical for sustainable application in the future. In this study, maize (Zea mays L.) plants were cultivated in field soils mixed with nZVI at 0, 50, and 500 mg/kg soil for four weeks. Upon exposure to 500 mg/kg nZVI, ICP-MS results showed that Fe accumulated by roots and translocated to leaves was increased by 36% relative to untreated controls. At 50 mg/kg, root elongation was enhanced by 150-200%; at 500 mg/kg, pigments, lipid peroxidation, and polyphenolic levels in leaves were increased by 12, 87 and 23%, respectively, whereas the accumulation of Al, Ca, and P were decreased by 62.2%, 19.7%, and 13.3%, respectively. A gas chromatography-mass spectrometry (GC-MS) based metabolomics analysis of maize roots revealed that antioxidants and stress signaling-associated metabolites were downregulated at 50 mg/kg, but were upregulated at 500 mg/kg. At 50 mg/kg, the content of glutamate was increased by 11-fold, whereas glutamine was decreased by 99% with respect to controls. Interestingly, eight metabolic pathways were disturbed at 50 mg/kg, but none at 500 mg/kg. This metabolic reprogramming at the lower dose represented potential risks to the health of exposed plants, which could be particularly important although no phenotypic impacts were noted. Overall, metabolites analysis provides a deeper understanding at the molecular level of plant response to nZVI and is a powerful tool for full characterization of risk posed to crop species as part of food safety assessment.


Pushing Droplet Through a Porous Medium.
I use a mechanical model of a soft body to study the dynamics of an individual fluid droplet in a random, non-wettable porous medium. The model of droplet relies on the spring-mass system with pressure. I run hundreds of independent simulations. I average droplets trajectories and calculate the averaged tortuosity of the porous domain. Results show that porous media tortuosity increases with decreasing porosity, similar to single-phase fluid study, but the form of this relationship is different. The online version contains supplementary material available at 10.1007/s11242-021-01705-z.


The effect of niclosamide on Echinococcus granulosus, Taenia hydatigena and Taenia ovis infections in dogs.
The effect of niclosamide (particle size 1 micron m) and its piperazine salt (particle size 5-10 micron m) on Echinococcus granulosus and Taenia hydatigena has been investigated. The piperazine salt of niclosamide was also tested for activity against Taenia ovis. These trials involved 326 dogs. Irrespective of particle size, the drug was found to be virtually inactive against 28-day-old E granulosus. Some evidence was found indicating that there may be a low degree of activity against 70-day-old worms. The drug was found to be effective at 32 mg/kg and 64 mg/kg against T hydatigena and 50 mg/kg against T ovis. Some evidence was obtained that milk decrease the efficiency of the piperazine salt against T hydatigena at the lower dose rates. Micronisation of the drug did not increase the efficiency against this parasite. Vomiting and diarrhoea were common sequelae.


Cyclic Change of Sphincter of Oddi Motility and Its Relationship with Small Bowel Migrating Motor Complex in Humans.
Several animal and human studies have reported that sphincter of Oddi (SO) motility shows cyclical changes during the fasting state. However, to date, the relationship between the SO motility and the migrating motor complex (MMC) of the small bowel (SB) remains unclear in humans. We observed SO motility over a long study period and evaluated its relationship with the MMC of the SB in humans using percutaneous long-term manometry. Our study included patients with hepatolithiasis who required percutaneous transhepatic catheter placement and subsequently underwent choledochoscopy and stone removal. Long-term percutaneous transhepatic SO manometry was performed after complete stone removal. SO and SB motility were simultaneously recorded. SO motility showed cyclical phasic changes with periodic high-frequency contractions similar to the MMC contractions of the SB. All high-frequency contractions of the SO coincided with phase III contractions of the MMC of the SB. The proportions of phase III contractions of SO and SB were similar, but the proportions of phase I (P = 0.001) and phase II (P = 0.002) contractions were significantly different. The mean basal SO pressure was observed to significantly increase in phase III compared to phase I (P = 0.001) and phase II (P = 0.001) contractions. SO motility in humans showed cyclical phasic changes closely coordinated with the MMC of the SB in a fasting state; however, the proportion of phases differed between the SO and the SB. The basal pressure significantly increased during physiological high-frequency phase III contractions of the SO.


Impact of exercise training on muscle function and ergoreflex in Fontan patients: a pilot study.
Several studies have demonstrated persistent reduced exercise capacity in Fontan patients even after surgical intervention. The purpose of this study was to evaluate if the skeletal muscle function of these patients is abnormal, if it correlates with exercise tolerance and if it can be improved by exercise training. We evaluated the functional capacity of seven patients who underwent Fontan procedure (age:16+/-5 years, mean+/-SD) and seven healthy children (19+/-7 years) paired for age, sex, height and weight. Evaluation included pulmonary evaluation, neuromuscular function and exercise tolerance. Secondly, an 8-week exercise training program was performed by five of these patients. The ergoreflex contribution to absolute diastolic blood pressure was higher (12.5+/-4.8 vs. 5.6+/-4.2 mmHg; p=0.04) in Fontan patients vs. healthy subjects whereas a trend was encountered regarding the ergoreflex contribution to absolute systolic blood pressure (9.0+/-7.0 vs. 0.4+/-9.0 mmHg; p=0.09). Furthermore, time to fatigue of the non-dominant forearm muscles was shorter in Fontan patients vs. healthy subjects (431+/-290 vs. 847+/-347 s; p=0.03). Following exercise training, there was a significant reduction of the ergoreflex contribution to absolute values of systolic blood pressure (9.8+/-0.9 vs. 0.3+/-2.7 mmHg; p<0.05). There was an association between muscle strength and VO2 peak in Fontan patients (upper limb: r=0.895; p<0.01; lower limb: r=0.838; p<0.05, respectively). Skeletal muscle function in Fontan patients is abnormal which may have an impact in the reduced exercise tolerance encountered in these patients. Exercise training may have beneficial impacts on the skeletal muscle function in this population.


Topical gel-based biomaterials for the treatment of diabetic foot ulcers.
Diabetic foot ulcers (DFUs) are a devastating ailment for many diabetic patients with increasing prevalence and morbidity. The complex pathophysiology of DFU wound environments has made finding effective treatments difficult. Standard wound care treatments have limited efficacy in healing these types of chronic wounds. Topical biomaterial gels have been developed to implement novel treatment approaches to improve therapeutic effects and are advantageous due to their ease of application, tunability, and ability to improve therapeutic release characteristics. Here, we provide an updated, comprehensive review of novel topical biomaterial gels developed for treating chronic DFUs. This review will examine preclinical data for topical gel treatments in diabetic animal models and clinical applications, focusing on gels with protein/peptides, drug, cellular, herbal/antioxidant, and nano/microparticle approaches. STATEMENT OF SIGNIFICANCE: By 2050, 1 in 3 Americans will develop diabetes, and up to 34% of diabetic patients will develop a diabetic foot ulcer (DFU) in their lifetime. Current treatments for DFUs include debridement, infection control, maintaining a moist wound environment, and pressure offloading. Despite these interventions, a large number of DFUs fail to heal and are associated with a cost that exceeds $31 billion annually. Topical biomaterials have been developed to help target specific impairments associated with DFU with the goal to improve healing. A summary of these approaches is needed to help better understand the current state of the research. This review summarizes recent research and advances in topical biomaterials treatments for DFUs.


Binding of products originating from the peroxidation of liver microsomal lipids to the non-lipid constituents of the microsomal membrane.
The binding of products derived from the peroxidation of liver microsomal lipids to the non-lipid constituents of the microsomes was studied. To this end arachidonic acid labelled with tritium at the positions of the double bonds was given to rats and allowed to incorporate into the membrane lipids of the liver cell. When liver microsomes containing labelled arachidonic acid were incubated aerobically in the NADPH-dependent system, a marked production of malonic dialdehyde (MDA) occurred and, concomitantly, there was a consistent release of radioactivity from the microsomes into the incubation medium. The addition of EDTA to the incubation medium prevented, to a large extent, both the MDA formation and the release of radioactivity. Chromatographic studies showed that the bulk of the radioactivity released from the incubated microsomes is not MDA. In the incubated microsomes, the radioactivity decreased in total lipids, while it increased by about 15 times in the non-lipoidal residue. A similar increase in radioactivity was seen in microsomal protein, while no increase was observed in microsomal RNA (the radioactivity was negligible in both the incubated and the non-incubated samples). It seems therefore that products originating from lipoperoxidation of arachidonic acid covalently bind to the microsomal protein. In order to investigate whether alterations similar to those observed in the in vitro peroxidation of liver microsomes could be detected in the in vivo intoxication with carbon tetrachloride, rats given labelled arachidonic acid as above, were poisoned with CCl4. Sixty minutes after poisoning, the radioactivity present in the microsomal lipids was generally lower in the intoxicated rats than in the controls, while the labelling of the non-lipoidal residue and of the protein was higher in the CCl4-poisoned rats.


Comparison of Calcium Phosphate and Zinc Oxide Nanoparticles as Dermal Penetration Enhancers for Albumin.
[This retracts the article , PMID: 26997697.].


In vitro assays to study role of T cell-derived factors on human B lymphocytes should take into consideration inhibiting effect of large granular lymphocyte subset (CD5-,CD16+) that can contaminate B cell preparations.
In these studies, the inhibitory role of a large granular lymphocyte (LGL) subset (CD5-,CD16+) on pokeweed mitogen (PWM)-induced B lymphocyte differentiation was examined. CD5-,CD16+ LGL cells are the predominant subset of LGL cells and are possibly distinct from other LGL subsets in that they lack B and T cell markers. CD5-,CD16+ LGL possess abundant FcIgG receptors and previous studies have clearly demonstrated that in the presence of insoluble immune complexes, this LGL subset will inhibit B lymphocyte differentiation in the presence of T cells. In the present studies, we analyzed the inhibiting role of CD5-,CD16+ LGL cells that had not been activated by immune complexes. B + L preparations obtained by removal of E rosette-forming T cells were further depleted of T lymphocytes by complement-dependent lysis of T cells using a monoclonal antibody reactive to total T cells (Leu-1, CD5 antigen, Becton-Dickinson). B lymphocytes in such B + L preparations failed to differentiate into plasma cells containing intracytoplasmic immunoglobulin (Ig), in the presence of PWM, T cell-derived helper supernatants (THS), and interleukin-2 (IL-2). However, B cells differentiated under these conditions, when B + L preparations were further depleted of CD5-,CD16+ LGL cells by complement-dependent lysis using a monoclonal antibody (Leu-11) reactive to CD16 antigen of FcIgG receptors present on LGL cells. These studies indicated that CD5-,CD16+ cells unlike the CD8-positive T suppressor cell, will directly inhibit B lymphocyte differentiation into plasmacytoid cells containing intracytoplasmic Ig when T lymphocytes are not present. However, addition of a few T lymphocytes (less than 10%) to purified B + L preparations abrogated the CD5-,CD16+ LGL cell inhibition of B cell differentiation.


Incidence of shoulder disorders in a cohort of healthcare workers from 2009 to 2020.
To estimate the incidence of shoulder disorders in a cohort of Health Care Workers (HCWs). 4406 workers employed from 2009 to 2020, were included in the study. Occupational risk factors and jobs were assessed according to working history. Incident cases were defined in case of shoulder pain associated with functional limitations during the medical examination. The Cox regression model was used to calculate the Hazard Ratio (HR) for different work activities, adjusted for age, sex, body mass index, and previous musculoskeletal injuries, using clerks as the reference category. The incidence rates of shoulder musculoskeletal disorder for men and women were 13.1 for 1000 person-years (CI 95% 10.6-16.3) and 20.1 for 1000 person-years (CI 95% 17.8-22.6) respectively. The adjusted HR was significantly increased with age (1.06, CI 95% 1.05-1.07), outpatient health activities (2.82, CI 95% 1.89-4.219), and wards health activity (2.37, CI 95% 1.68-3.33). HCWs with high biomechanical risk such as nurses and healthcare assistants had a higher incidence of shoulder disorders. Actions are needed for better prevention in health care assistance.


The fear-inhibited light reflex: importance of the anticipation of an aversive event.
It has been shown previously that the amplitude of the pupillary light reflex response decreases when subjects anticipate an aversive stimulus (i.e. electric shock), compared to periods when subjects are resting ('fear-inhibited light reflex'). To compare the effects of the anticipation of an electric shock (putative aversive event) and of an acoustic stimulus (putative neutral event) on the light reflex. Twelve healthy volunteers participated in a training session and an experimental session. Pupil diameter was monitored with infra-red binocular television pupillometry. The experimental session consisted of 14 blocks of 3 light stimuli. 'Relaxation' (no anticipation) and 'anticipation' (electrical or acoustic stimulus) blocks alternated. Mood and feelings were self-rated on visual analogue scales. The anticipation of the electrical stimulus was associated with increases in initial pupil diameter and subjectively rated 'anxiety' and 'alertness', and a decrease in the amplitude of the pupillary light reflex response, whereas anticipation of the acoustic stimulus was associated with increases in initial pupil diameter and subjective 'alertness' only. The increase in initial pupil diameter is related to the anticipation of any stimulus, whereas the decrease in the amplitude of the light reflex response is associated with the aversiveness of the anticipated stimulus.


The Consumption of Food-Based Iodine in the Immediate Pre-Pregnancy Period in Madrid Is Insufficient. San Carlos and Pregnancy Cohort Study.
A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age). Between 2015-2017, 2523 normoglycemic women out of 3026 eligible had data in the modified Diabetes Nutrition and Complication Trial (DNCT) questionnaire permitting assessment of pre-gestational food-based iodine consumption, and were included in this study. Daily food-based iodine intake was 123 ± 48 µg, with 1922 (76.1%) not reaching 150 µg/day. Attaining this amount was associated with consuming 8 weekly servings of vegetables (3.84; 3.16-4.65), 1 of shellfish (8.72; 6.96-10.93) and/or 2 daily dairy products (6.43; 5.27-7.86). Women who reached a pre-gestational intake ≥150 µg had lower rates of hypothyroxinemia (104 (17.3%)/384 (21.4%); p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67-0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.


The origins and nature of acupuncture in dentistry.
A description is given of the origins and different types of acupuncture. The historical origins and their application in dentistry are discussed.


A case study of using the He Pikinga Waiora Implementation Framework: challenges and successes in implementing a twelve-week lifestyle intervention to reduce weight in Māori men at risk of diabetes, cardiovascular disease and obesity.
Māori men have stark health inequities around non-communicable diseases. This study describes the case of a partnership attempting to develop and implement a culturally centred intervention through a collaborative partnership to potentially address the inequities. In particular, the partnership followed a participatory, co-design approach using the He Pikinga Waiora (HPW) Implementation Framework; the study presents lessons learnt in addressing health inequities following this framework. The partnership involved a university research team and a Māori community health provider. They engaged with other stakeholders and several cohorts of Māori men through a co-design process to adapt a 12-week lifestyle intervention. The co-design process was documented through meeting notes and interviews with partners. Two cohorts participated in separate single group pre-intervention/post-intervention designs with multi-method data collection. Key outcome measures included weight loss, self-reported health, physical activity, and nutrition. Post-intervention data collection included qualitative data. The co-design process resulted in a strong and engaged partnership between the university team and the provider. There were significant challenges in implementing the intervention including having two additional partner organisations dropping out of the partnership just after the initial implementation phase. However, a flexible and adaptable partnership resulted in developing two distinct lifestyle interventions run with 32 Māori men (in two different cohorts of 8 and 24). All but one in the first cohort completed the programme. The first cohort had a modest although statistically insignificant improvement in weight loss (d = 1.04) and body mass index (BMI; d = 1.08). The second cohort had a significant reduction in weight loss (d = 1.16) and BMI (d = 1.15). They also had a significant increase in health-related quality of life (d = 1.7) and self-rated health (d = 2.0). The HPW Framework appears to be well suited to advance implementation science for Indigenous communities in general and Māori in particular. The framework has promise as a policy and planning tool to evaluate and design interventions for chronic disease prevention in Indigenous communities. Despite this promise, there are structural challenges in developing and implementing interventions to address health inequities. Retrospectively registered, Australia New Zealand Clinical Trials Registry, ACTRN12619001783112.


Relationship between foot morphology, muscle strength, and physical performance test in women aged 65 years and older: a cross-sectional study.
Hallux valgus is a foot deformity that may affect gait, thus increasing the risk of falls among older people. We investigated the relationship between foot morphology, muscle strength, and physical performance. In this study, community-dwelling older people aged ≥65 years were included. A three-dimensional footprint automatic measurement apparatus was used to measure the hallux valgus angle, arch height ratio, and heel-floor angle. Furthermore, the toe flexor strength and ankle plantar flexion strength were measured. Physical performance tests included the five-repetition sit-to-stand test, one-leg standing time, maximal step length, functional reach test, and 5-m fastest walking time (walking time). The relationship between the hallux valgus angle and foot morphology and muscle strength was examined. In addition, factors affecting physical performance testing were assessed. Two-group comparisons, correlation, and multiple comparisons were used for statistical analyses. Of the 133 women (age 77.7 ± 6.2 years), 57 had hallux valgus and 76 had no hallux valgus. There was a significant difference in the arch height ratio and heel-floor angle between women with and without hallux valgus (p < 0.001). A correlation was found between the hallux valgus angle and the heel-floor angle (r = 0.468, p < 0.001) and arch height ratio (r = - 0.337, p < 0.001), respectively. Multiple regression analysis showed that the hallux valgus angle was related to functional reach (β = - 0.162, p = 0.042), and toe flexor strength was related to five-repetition sit-to-stand (β = - 0.182, p = 0.036), maximal step length (β = 0.328, p < 0.001), and walking time (β = - 0.219, p = 0.006). A relationship was found between the hallux valgus angle, arch height rate, and inward inclination angle of the calcaneus. Functional reach was predicted based on the hallux valgus angle, whereas the five-repetition sit-to-stand, maximal step length, and walking time were predicted based on toe flexor strength. Hallux valgus predicted not only the forefoot but also the foot morphology and was related to physical performance. From the perspective of motor function and fall prevention, efforts should be made to better understand and prevent the onset and progression of hallux valgus.


A novel superfamily of transporters for allantoin and other oxo derivatives of nitrogen heterocyclic compounds in Arabidopsis.
A wide spectrum of soil heterocyclic nitrogen compounds are potential nutrients for plants. Here, it is shown that Arabidopsis plants are able to use allantoin as sole nitrogen source. By functional complementation of a yeast mutant defective in allantoin uptake, an Arabidopsis transporter, AtUPS1 (Arabidopsis thaliana ureide permease 1), was identified. AtUPS1 belongs to a novel superfamily of plant membrane proteins with five open reading frames in Arabidopsis (identity, 64 to 82%). UPS proteins have 10 putative transmembrane domains with a large cytosolic central domain containing a "Walker A" motif. Transport of (14)C-labeled allantoin by AtUPS1 in yeast exhibited saturation kinetics (K(m) approximately 52 microM), was dependent on Glc and a proton gradient, and was stimulated by acidic pH. AtUPS1 transports uric acid and xanthine, besides allantoin, but not adenine. Protons are cosubstrates in allantoin transport by AtUPS1, as demonstrated by expression in Xenopus laevis oocytes. In plants, AtUPS1 gene expression was dependent on the nitrogen source. Therefore, AtUPS1 presumably is involved in the uptake of allantoin and other purine degradation products when primary sources are limiting.


Innate immune responses and efficacy of using mushroom beta-glucan mixture (MBG) on orange-spotted grouper, Epinephelus coioides, aquaculture.
This study attempts to describe the effects of innate immunity responses and field application of mushroom beta-glucan mixture (MBG) in cultured orange-sported grouper, Epinephelus coioides. Chemical analysis for MBG showed that the mixture contains 34.06% of macro-molecular polymers with bio-active linkage such as 3-; 3,4- and 4,6-glucopyranosyl and 6-linked galactopyranosyl residues. Study performed on the innate immunity showed that oral ingestion of MBG at 1.0 g and 2.0 g per kilogram of feed levels may significantly enhance the lysozyme activity, alternative complement activity, phagocytic activity and respiration burst of the experimental groupers. Observation on the experimental challenge of pathogen showed that uses of MBG at 0.1% and 0.2% levels in feed might significantly enhance the protection of grouper against Vibrio alginolyticus. Field trials performed on short and long-term culture showed that feeding of diet containing 0.1% or 0.2% of MBG may significantly enhance the survival of cultured groupers up to 16% when compared with those obtained from controls.


Altered behaviors in male mice, male quail, and salamander larvae following early exposures to the estrogenic pesticide methoxychlor.
Numerous publications show that methoxychlor (MXC), in use today as a DDT substitute, is a reproductive toxicant; it produces deleterious effects on the structure and function of the reproductive organs in exposed species. Exposure of mice (33 mg/kg body weight) to purified (95%) MXC at the time of implantation, or injection, of 5 mg MXC into freshly laid quail eggs prior to artificial incubation, altered sexual arousal and sexual behavior in adult males of both species. When placed near a plastic partition with an estrus female behind it, the MXC-exposed male mice showed no sexual arousal, spent less time near the partition, and exhibited lower testosterone levels. Similarly, adult quail males that were exposed to MXC during incubation showed a lack of sexual interest and copulatory behavior when presented with a receptive female. Some males showed a longer latency period before mounting the female, while others did not show any sexual interest at all. Exposure of salamander embryos to purified MXC at or above 0.3 microM (0.1 mg/l) induced precocial hatching of embryos and reduced the startle response and the distance traveled in response to startle. Exposing hatched larvae to MXC for 3 days also resulted in a blunted startle response. Due to the blunted startle response and decreased avoidance travel, the exposed salamander larvae appear more susceptible to predation and these effects may contribute to amphibian population declines. The results of these studies indicate that developmental exposures to environmental chemicals with hormonal activities produce undesirable behaviors that may affect population dynamics and survivability of exposed species.


Pregnancy after lower urinary tract reconstruction in women.
We determined if pregnant women with reconstructed lower urinary tracts experience complications related to the urological reconstruction. A total of 27 women (34 pregnancies) with reconstructed lower urinary tracts underwent regular urinalysis, blood biochemistry studies and ultrasound examinations during pregnancy and for a minimum of 1 year after delivery. There were 28 normal, full-term vaginal deliveries without complication. A total of 6 patients underwent cesarean section, with injury to the vascular pedicle of the cystoplasty without sequelae occurring in 1. Temporary postpartum incontinence occurred in 6 patients. Patients with reconstructed lower urinary tracts can experience normal deliveries but require close surveillance. The route of delivery should be determined by obstetrical indications.


Mouse monoclonal anti-N. I. Production and serological characterization.
Two examples of mouse monoclonal anti-N are described. The antibodies were derived from mice immunized with sialoglycoprotein extracts of group O MM ss erythrocyte membranes and the probable stimulus for immunization was glycophorin B associated N-antigen. Both antibodies reacted as direct agglutinins but appeared to recognize different epitopes with one having a greater dependence on sialic acid. The antibodies could prove to be valuable alternatives to those reagents used currently for N-blood grouping.


Electroconvulsive seizures induce angiogenesis in adult rat hippocampus.
Electroconvulsive seizure (ECS)-treatment, a model for electroconvulsive therapy (ECT) has been shown to induce proliferation of endothelial cells in the dentate gyrus (DG) of adult rats. Here we quantified the net angiogenic response after chronic ECS-treatment in the molecular layer (ML) of the dentate gyrus. Patients undergoing ECT are routinely oxygenated to prevent hypoxia, a known inducer of angiogenesis. Therefore we also examined the effect of oxygenation on ECS-induced proliferation of endothelial cells. Total endothelial cell numbers and vessel length were estimated utilizing design based stereological analysis methods. Endothelial cell proliferation in the DG after ECS with or without oxygenation was assessed using bromodeoxyuridine. The total number of endothelial cells and total vessel length was increased. Oxygenation did not abolish the ECS-induced proliferation of endothelial cells in the DG. ECS-treatment induces a dramatic increase in endothelial cell proliferation leading to a 30% increase in the total number of endothelial cells. The increase in cell number resulted in a 16% increase in vessel length. These findings raise the possibility that similar vascular growth is induced by clinically administered ECT.


Relation between essential fatty acid metabolism and gastrointestinal symptoms in cystic fibrosis.
Studies in our laboratory have supported the hypothesis, that the basic defect in cystic fibrosis increases the metabolism of essential fatty acids and thereby gradually gives rise to essential fatty acid deficiency, which is a well documented finding in most cases with this disease. Both the increased metabolism--giving high liberation of arachidonic acid and its metabolic products, i.e. different eicosanoids--and the subsequent essential fatty acid deficiency will cause gastrointestinal symptoms and the sequence of this development will mirror the natural history of the disease. Clinical data and results from animal research are discussed in relation to gastrointestinal symptoms and signs of cystic fibrosis.


Transcranial stimulation of alpha oscillations up-regulates the default mode network.
The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.


Early Life Programming of Skeletal Health.
Increasing bone mineral accrual during childhood might delay the onset of osteoporosis. We discuss the scientific evidence for early life approaches to optimising skeletal health. There is an ever-growing body of evidence from observational studies suggesting associations between early life exposures, particularly during foetal development, and bone mineral density (BMD). The findings of such studies are often heterogeneous, and for some exposures, for example, maternal smoking and alcohol intake in pregnancy or age at conception, intervention studies are not feasible. The most frequently studied exposures in intervention studies are calcium or vitamin D supplementation in pregnancy, which overall suggest positive effects on offspring childhood BMD. Maternal calcium and/or vitamin D supplementation during pregnancy appear to have positive effects on offspring BMD during early childhood, but further long-term follow-up is required to demonstrate persistence of the effect into later life.