Prioritizing key synergistic circulating microRNAs for the early diagnosis of biliary tract cancer.
Biliary tract cancer (BTC) is a highly aggressive malignant tumor. Serum microRNAs (ser-miRNAs) serve as noninvasive biomarkers to identify high risk individuals, thereby facilitating the design of precision therapies. The study is to prioritize key synergistic ser-miRNAs for the diagnosis of early BTC. Sampling technology, significant analysis of microarrays, Pearson Correlation Coefficients, t-test, decision tree, and entropy weight were integrated to develop a global optimization algorithm of decision forest. The source code is available at https://github.com/SuFei-lab/GOADF.git. Four key synergistic ser-miRNAs were prioritized and the synergistic classification performance was better than the single miRNA' s. In the internal feature evaluation dataset, the area under the receiver operating characteristic curve (AUC) for each single miRNA was 0.8413 (hsa-let-7c-5p), 0.7143 (hsa-miR-16-5p), 0.8571 (hsa-miR-17-5p), and 0.9365 (hsa-miR-26a-5p), respectively, whereas the synergistic AUC value increased to 1.0000. In the internal test dataset, the single AUC was 0.6500, 0.5125, 0.6750, and 0.7500, whereas the synergistic AUC increased to 0.8375. In the independent test dataset, the single AUC was 0.7280, 0.8313, 0.8957, and 0.8303, and the synergistic AUC was 0.9110 for discriminating between BTC patients and healthy controls. The AUC for discriminating BTC from pancreatic cancer was 0.9000. Hsa-miR-26a-5p was a predictor of prognosis, patients with high expression had shorter survival than those with low expression. In conclusion, hsa-let-7c-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-26a-5p may act as key synergistic biomarkers and provide important molecular mechanisms that contribute to pathogenesis of BTC.


Design of flexible hollow core fiber based photoacoustic gas sensor with high cell constant and compact size.
Here we designed, optimized, and proposed a flexible low frequency resonant photoacoustic (PA) gas sensor by using a large core leaky hollow core fiber (L-HCF). The influences from the dimensions, the transmission loss and the bending loss on the performance of the flexible PA gas sensor were systematically investigated. In this work, the optimized inner diameter and length of the L-HCF were 1.7 mm and 300 mm, respectively. The L-HCF based PA cell constant was calculated to be 12115 Pa/(W·cm-1). The minimum detectable limit (MDL) for trace C2H2 detection achieved 23.0 ppb when the lock-in integration time was 200 s by using a near-infrared distributed feedback (DFB) laser source and a low-cost electrical micro-electro-mechanical system (MEMS) microphone. Besides, the amplitude decay ratio of the of the PA signal was only 11.3% when the bending radius of the L-HCF was 100 mm. The normalized noise equivalent absorption (NNEA) coefficient is calculated to be 6.6 × 10-9 W•cm-1•Hz-1/2. The L-HCF based PA cell was proved to own merits of compact size, high cell constant, small gas volume and low cost.


Cartap removal from simulated water matrices by fluidized-bed Fenton process: optimization of process parameters.
Cartap is a thiocarbamate pesticide widely-used to protect rice crops, one of the most mass-produced cereals worldwide. Effluents containing cartap pose serious environment and health risks due to the acute toxicity of this emerging contaminant. This work evaluates the capabilities of the Fenton process to efficiently remove cartap from water matrices. Process parameters such as hydrogen peroxide dosage, ferrous ion concentration and operating pH were optimized using Box-Behnken design. Results showed complete cartap removal with Fenton oxidation in a fluidized-bed reactor while eliminating sludge generation during treatment. Fluidized-bed Fenton process had improved reduction in chemical oxygen demand and total organic carbon due to the contribution of heterogeneous Fenton catalysis to the overall degradation of cartap species compared to conventional Fenton in a batch reactor. Furthermore, competitive reactions and scavenging effects in complex natural water matrices were simulated with the use of inorganic ions such as nitrate, chloride, and phosphate. Results demonstrated the detrimental effect of phosphate ions on Fenton oxidation due to the precipitation of soluble catalysts as iron phosphates, which stops the catalytic Fenton cycle and thus the production of oxidants for contaminant degradation.


Vitamin D Status Is Associated with Hepcidin and Hemoglobin Concentrations in Children with Inflammatory Bowel Disease.
Anemia, iron deficiency, and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through downregulatory effects on hepcidin and proinflammatory cytokines. We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data were obtained from N = 69 patients with IBD aged 5 to <19 years. Iron biomarkers (ferritin, soluble transferrin receptor), and 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers (C-reactive protein and α-1-acid glycoprotein), hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. Approximately 50% of subjects were inflamed (C-reactive protein >5 mg/L or α-1-acid glycoprotein >1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin <15 μg/L or soluble transferrin receptor >8.3 mg/L) was 67%; anemia was 36%, and vitamin D insufficiency (25(OH)D <30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (β [SE] = -0.9 [0.5], P = 0.046), controlling for age, sex, race, insurance status, body mass index for age, inflammation, disease diagnosis (ulcerative colitis versus Crohn's disease), and disease duration, compared with 25(OH)D ≥30 ng/mL. Our results suggest that concentrations of 25(OH)D ≥30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status, and anemia in pediatric IBD.


Progressive multifocal leukoencephalopathy developing in a fludarabine naïve patient with chronic lymphocytic leukemia.
We report a case of progressive multifocal leukoencephalopathy developing in a fludarabine-naïve patient with chronic lymphocytic leukemia. We suggest that progressive multifocal leukoencephalopathy should be considered in any chronic lymphocytic leukemia patient with unexplained neurological symptoms. Treatment history does not necessarily require fludarabine. Intrathecal cytosine arabinoside although unsuccessful in this patient, is a therapeutic option to consider in patients experiencing side effects from systemic therapy.


Does a cluster always equal a cluster? Geographical variation of cluster populations.
Aims and method To provide information regarding the extent to which the process of clustering using the mental health clustering tool captures the complexity of patient need across different geographical areas. Investigation was undertaken via a 'deep dive' into patient notes, with data collected on patients allocated to cluster 5, 8 or 13 in three different London boroughs. Results There is evidence for within-cluster differences between patients in different London boroughs in terms of various complexity factors. Further findings in relation to accuracy of clustering suggest some area-specific patterns in terms of clustering practice, raising the possibility that clinicians have different scoring thresholds in different areas. Clinical implications Complexity factors can affect resource use and therefore cost of service provision. In the case of a national tariff, providers of care to more complex patients may be placed at greater financial risk. It is therefore likely that some form of tariff adjustments will need to be introduced so as not to disadvantage patients and clinicians practising in areas of greater complexity.


Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats.
While it is well known that sepsis inhibits serum IGF-I and its gene expression in the liver, the effect on pituitary GH and IGF-binding protein-3 (IGFBP-3) is poorly understood. The GH-IGF-I-IGFBP-3 response to different doses of lipopolysaccharide (LPS) administration has been investigated in adult male rats. Two experiments were performed, administration of low doses of LPS (5, 10, 50 and 100 microg/kg) and high doses of LPS (100, 250, 500 and 1000 microg/kg). Rats received two i.p. injections of LPS (at 1730 h and 0830 h the following day) and were killed 4 h after the second injection. LPS administration induced a biphasic response in serum concentrations of GH, with an increase at the 10 microg/kg dose, followed by a decrease at higher doses (100 microg/kg on up). Pituitary GH mRNA was also increased by the administration of 10 and 50 microg/kg LPS, whereas at higher doses LPS did not modify pituitary GH mRNA. We also analyzed the GH response to LPS in primary pituitary cell cultures. When exposed to LPS, in the culture medium, there was an increase in GH release at the concentration of 0.1 and 10 ng/ml, whereas more concentrated LPS did not modify GH release. Serum concentrations of IGF-I declined in a dose-dependent fashion after LPS administration in the rats injected with 10 microg/kg LPS on up. This decrease is secondary to modifications in its synthesis in the liver, since endotoxin injection decreased both IGF-I and its mRNA in the liver. The liver GH receptor mRNA was also decreased by LPS administration, but only in the animals injected with high LPS doses. There was a decrease in both the IGFBP-3 serum levels and its gene expression in the liver with all LPS doses studied. These data suggest a biphasic LPS effect on pituitary GH, a stimulatory effect at low doses and an inhibitory effect at higher doses, whereas it has a clear inhibitory effect on IGF-I and IGFBP-3 synthesis in the liver. The decrease in liver IGFBP-3 mRNA and in serum concentrations of IGFBP-3 in the rats injected with LPS may contribute to the decrease in serum concentrations of IGF-I.


Highly Efficient Catalytic Hydrogen Evolution from Ammonia Borane Using the Synergistic Effect of Crystallinity and Size of Noble-Metal-Free Nanoparticles Supported by Porous Metal-Organic Frameworks.
A series of nonprecious metal nanoparticles (NPs) supported by metal-organic framework MIL-101 were synthesized using four methods and their catalytic performance on hydrogen evolution from ammonia borane (NH3BH3) was studied. The results showed that the crystalline Co NPs with size of 4.5-8.5 and 14.5-24.5 nm had low activities featuring the total turnover frequency (TOF) values of 9.9 and 4.5 molH2 molcat-1 min-1, respectively. In contrast, the amorphous Co NPs with size of 1.6-2.6 and 13.5-24.5 nm exhibited high activities featuring the total TOF values of 51.4 and 22.3 molH2 molcat-1 min-1, respectively. The remarkably different activities could be ascribed to the different crystallinity and size of Co NPs in the catalysts. Moreover, the ultrasound-assisted in situ method was also successfully applied to bimetallic systems, and MIL-101-supported amorphous CuCo, FeCo and NiCo NPs had the catalytic activities with total TOF values of 51.7, 50.8, and 44.3 molH2 molcat-1 min-1, respectively, which were the highest in the values of the reported non-noble metal Co-based catalysts. The present approach, namely, using the synergistic effect of crystallinity and size of metal NPs, may offer a new prospect for high-performance and low-cost nanocatalysts.


[Molluscum contagiosum. Clinicopathologic and ultrastructural study].
26 usually multiple Molluscum contagiosum (MC) lesions corresponding to 14 patients (x age, 12 years old) mainly located in face and body, and unfrequently in genital area, were studied. Under light microscopy, we emphasize the presence of molluscum bodies corresponding ultrastructurally to large bodies of viral particles within a protein matrix. Intranuclear inclusions of suspected viral origin were noted too. Lesions previously embedded in paraffin showed a perfect preservation of their viral particles.


Ureteral stenosis secondary to common iliac aneurysm: a case report and review of the literature in Japan.
A case of right ureteral obstruction secondary to right common iliac aneurysm presenting as right hydronephrosis is reported and the literature is reviewed. A 66-year-old man was admitted to our hospital with lower abdominal pain and was treated by bypass operation with artificial vessel and uretero-ureterostomy of right ureter under the diagnosis of right ureteral stenosis secondary to right iliac aneurysm. Histological examination showed arteriosclerotic aneurysm and a fibrillary inflammatory change in peri-ureteral tissue without any hemosiderin-laden macrophages. Intravenous pyelography showed improvement of right hydronephrosis 45 days after operation. To date 11 cases including our case have been reported in Japan, 10 in males and the other in a female. Initial symptoms were either lumbago or an abdominal mass with palpitation in many cases. The treatment was by resection of aneurysm with bypass grafting or ureterolysis.


A Dichotomy of Information-Seeking and Information-Trusting: Stem Cell Interventions and Children with Neurodevelopmental Disorders.
Parents and primary caregivers of children with Cerebral Palsy (CP) and Autism Spectrum Disorder (ASD) are faced with difficult treatment choices and management options for their children. The potential of stem cell technologies as an interventional strategy for CP and ASD has gained attention in the last decade. Information about these interventions varies in quality, resulting in a complex landscape for parent decision making for a child's care. Further complicating this landscape are clinics that advertise these interventions as a legitimate treatment for a fee. In this study, we surveyed individuals who considered taking their child with ASD or CP abroad for stem cell interventions on their use of different sources of stem cell related health information and their level of trust in these sources. Participants reported that while the Internet was their most frequent source of information, it was not well-trusted. Rather, information sources trusted most were researchers and the science journals in which they publish, other parents of children with CP and ASD, and healthcare providers. These findings highlight a dichotomy between information-seeking preferences and information-trusted sources. We discuss the challenges of health science communication and present innovative opportunities to increase communication with trusted and reliable sources as part of an integrated multi-pronged approach.


Comparison of the effects of low dose interferon and high dose interferon on reduction of the number and size of plaques in patients with Multiple Sclerosis: A historical cohort.
Background: This study was performed to compare the effects of low dose interferon beta-1 (IFN-β-1) (CinnoVex, 30 mcg) and high dose IFN-β-1 (REBIF, 44 mcg) on the reduction of the number and size of plaques in magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS). Methods: This historical cohort study, which was performed in 2014 in Sanandaj (western part of Iran). 43 MS patients in two groups were investigated. The first group, which included 19 patients, was treated using high dose IFN (44 mcg) and the second group, which was consisted of 24 patients, was treated using low dose IFN (30 mcg). Patients' data were collected and analyzed by the Stata version 11 software; the analyses were performed using statistical t-test, chi-square test, Fisher test, and logistic regression. Results: Both drugs were effective in controlling active demyelinating plaque and in preventing plaque activation (P = 0.633). The impact of both drugs in the reduction of the number and size of plaques was evaluated. Based on the results of the MRI, high dose IFN therapy was more effective than the low dose IFN drugs and had a better performance in terms of reducing the number of plaques and in stop-and-recovery (P = 0.039), as well as in reducing the plaque size (P = 0.050). Conclusion: The high dose IFN therapy was more effective than the low dose IFN therapy in reducing the number and size of brain plaques in patients with relapsing-remitting MS (RRMS).


DOTS in Cambodia. Directly observed treatment with short-course chemotherapy.
Since the 1970s, Cambodia, a country of 10 million people in South East Asia, has experienced war, genocide and the virtual dismantling of the health system. It has a severe tuberculosis (TB) problem, with a new tuberculosis case notification rate, all forms, of about 150 per 100000 population and a tuberculosis programme, established in the early 1980s, achieving cure rates of only 40-50% in the last decade. To describe the implementation of a DOTS programme (directly observed treatment with short-course chemotherapy) under difficult conditions and its rapid success on a nation-wide scale. The World Health Organisation's recommended strategy was implemented in a phased manner throughout the country from 1994. The resources for TB drugs and running costs came from 13 sources. The DOTS strategy was gradually introduced after training and with regular supervision into 120 TB units inside general public hospitals at provincial and district level, after a mapping exercise; 75% of tuberculosis cases, all forms, are hospitalized during the entire initial phase and 85% of the total number of tuberculosis cases received free food from the World Food Programme. Two and a half years after the start of the new programme, DOTS was implemented in 85% of all public hospitals. In 1996, case-detection rates had reached 127 smear-positive PTB (pulmonary tuberculosis) and 149 PTB all forms per 100000 inhabitants; 90% of all tuberculosis patients received DOTS. From January 1994 to June 1995, 4164 new cases started category 1 treatment (2ERHZ/6EH). Of these, 89% were cured or completed treatment, 5% defaulted, 3% died, 1% were treatment failures and 2% transferred out. The DOTS strategy can be successfully implemented in even very difficult conditions such as those found in Cambodia.


Effectiveness of Mobile Apps in Promoting Healthy Behavior Changes and Preventing Obesity in Children: Systematic Review.
Mobile apps have been increasingly incorporated into healthy behavior promotion interventions targeting childhood obesity. However, their effectiveness remains unclear. This paper aims to conduct a systematic review examining the effectiveness of mobile apps aimed at preventing childhood obesity by promoting health behavior changes in diet, physical activity, or sedentary behavior in children aged 8 to 12 years. MEDLINE, Embase, PsycINFO, CINAHL, and ERIC were systematically searched for peer-reviewed primary studies from January 2008 to July 2021, which included children aged 8 to 12 years; involved mobile app use; and targeted at least one obesity-related factor, including diet, physical activity, or sedentary behavior. Data extraction and risk of bias assessments were conducted by 2 authors. Of the 13 studies identified, most used a quasi-experimental design (n=8, 62%). Significant improvements in physical activity (4/8, 50% studies), dietary outcomes (5/6, 83% studies), and BMI (2/6, 33% studies) were reported. All 6 multicomponent interventions and 57% (4/7) of standalone interventions reported significant outcomes in ≥1 behavioral change outcome measured (anthropometric, physical activity, dietary, and screen time outcomes). Gamification, behavioral monitoring, and goal setting were common features of the mobile apps used in these studies. Apps for health behavior promotion interventions have the potential to increase the adoption of healthy behaviors among children; however, their effectiveness in improving anthropometric measures remains unclear. Further investigation of studies that use more rigorous study designs, as well as mobile apps as a standalone intervention, is needed.


Influence of retinoids on sister chromatid exchanges and chromosomes in cultured human embryonic palatal mesenchymal cells.
The cytogenetic effects of retinoids and their metabolites on human embryonic palatal mesenchymal (HEPM) cells were investigated in cell culture. Treatment with 13-cis, 4-oxo-13-cis-, and all-trans-retinoic acids did not induce chromosomal structural aberrations even at high concentrations in the presence or absence of metabolic activation system. The frequencies of sister chromatid exchanges (SCE) tended to decrease in HEPM cells treated with retinoids in the absence of S-9. 4-Oxo-13-cis-retinoic acid, which is one metabolite of 13-cis-retinoic acid, significantly decreased the SCE frequencies. The mitotic index decreased with increasing concentration of retinoic acids, indicating that retinoids inhibit cell proliferation in HEPM cells. We concluded that retinoids inhibit cell proliferation in HEPM cells in culture without causing DNA or chromosome damage.


[Health care based on patients' needs].
Survival is not enough. We need to build a health system starting from patients' needs without wasting the resources of our grandchildren and great-grandchildren. We have to switch from curative to preventive medicine by firing managers who think they can resolve all problems by cutting expenditures. We need to educate a new cadre of managers able to govern by centering the system on the patients. Managers should consider health care as an asset and should reinforce clinical research. Such a program has been recently adopted in France.


Fetal anatomy of the upper pharyngeal muscles with special reference to the nerve supply: is it an enteric plexus or simply an intramuscular nerve?
We examined pharyngeal nerve courses in paraffin-embedded sagittal sections from 10 human fetuses, at 25-35 weeks of gestation, by using S100 protein immunohistochemical analysis. After diverging from the glossopharyngeal and vagus nerves at the level of the hyoid bone, the pharyngeal nerves entered the constrictor pharyngis medius muscle, then turned upward and ran superiorly and medially through the constrictor pharyngis superior muscle, to reach either the levator veli palatini muscle or the palatopharyngeus muscle. None of the nerves showed a tendency to run along the posterior surface of the pharyngeal muscles. Therefore, the pharyngeal nerve plexus in adults may become established by exposure of the fetal intramuscular nerves to the posterior aspect of the pharyngeal wall because of muscle degeneration and the subsequent rearrangement of the topographical relationship between the muscles that occurs after birth.


Reversible antifertility effect of aqueous leaf extract of Allamanda cathartica L. in male laboratory mice.
The efficacy of oral administration of aqueous leaf extract of Allamanda cathartica (150 mg kg(-1) body weight day(-1) for 14, 28 and 42 days) in inducing infertility and changes in various male reproductive endpoints was evaluated in Parkes strain mice. The effect of the treatment on organ weight, histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and on fertility indices was assessed. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same sections. The treatment also had adverse effects on motility, viability, morphology and on number of spermatozoa in the cauda epididymidis. Serum levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine, haematological parameters and liver and kidney histoarchitecture were, however, not affected by the treatment. Fertility of the extract-treated males was also suppressed, although the libido remained unaffected. By 56 days of treatment withdrawal, however, the above parameters recovered to control levels. Our results thus suggest that A. cathartica treatment causes reversible suppression of fertility in male mice, without causing detectable toxic effects.


[Fatherless: long-term sequelae in German children of World War II].
In World War II, 2.5 million children in Germany lost their fathers. Most of them grew up with their single mother, often accompanied by financial hardship. In a questionnaire carried out in 2003 in persons born before 1947, a rate of 19 % reported that they grew up with their mother alone. The present study examines whether long-term sequelae can be observed in these persons. Therefore, a representative sample of 883 subjects with an average age of 68 was questioned about psychiatric symptoms (SCL-27), loss of father and experiences during the war. Subjects reporting a loss of father had consistently more psychiatric symptoms. Three out of the six subscales of the SCL-27 displayed highly significant differences (depressive symptoms, symptoms of social phobia, symptoms of mistrust). Vegetative symptoms were also higher, but the effect was less pronounced. Agoraphobic and dysthymic symptoms did not show significantly higher values. It can be concluded that growing up without a father may have life-long consequences.


The maximum surgical blood order schedule and surgical blood use in the United States.
The outdating of units of blood can be reduced by decreasing the amount of time they spend in an assigned or crossmatched status. This reduction can be achieved in a hospital by establishing a maximum surgical blood order schedule (MSBOS) which reduces the excessive number of units of blood crossmatched preoperatively for patients undergoing elective surgery. The various steps which occurred in the development of a MSBOS in a large general hospital are detailed and the projected reduction in the number of crossmatched units which can be achieved with the MSBOS is illustrated. illustrated. The projected number of units of blood transfused to patients during their hospitalization for 50 common primary surgical procedures in the United States during 1974 is presented as a basis for defining maximum blood orders for each procedure.


Water oxidation catalysis: effects of nickel incorporation on the structural and chemical properties of the α-Fe₂O₃(0001) surface.
Photoelectrochemical solar fuel synthesis devices based on photoactive hematite (α-Fe2O3) anodes have been extensively investigated, yet a fundamental understanding regarding its associated water oxidation surface reaction mechanism is still lacking. To help elucidate detailed reaction mechanisms, we studied water chemisorption and reaction as well as structural changes induced by Ni incorporation into the α-Fe2O3(0001) surface. Investigation by scanning probe and electron diffraction techniques show that vapor deposition of Ni and subsequent annealing to 700 K leads to the interdiffusion and incorporation of Ni into the near-surface region of hematite and changes the structure of the (0001) surface by the formation of FeO-like domains on the topmost layer. These results are discussed in the context of a proposed water oxidation mechanism on this surface in which Ni doping facilitates water oxidation by increasing O hole concentrations and forms less negatively charged O anions (*O) and *O···OH species [ Liao, P. L.; Keith, J. A.; Carter, E. A. J. Am. Chem. Soc. 2012 , 134 , 13296 - 13309 . ]. Consistent with predictions from this theory, electrochemical measurements using cyclic voltammetry carried out on the ultrahigh vacuum-prepared surfaces demonstrated that Ni incorporation leads to higher current density and lower onset potential than the unmodified α-Fe2O3 surface. Our work utilizing a surface science approach helps to connect such theoretical predictions of reaction thermodynamics on well-defined structures and the performance of modified hematite model electrocatalysts for water oxidation.


p-Coumaric acid prevents obesity via activating thermogenesis in brown adipose tissue mediated by mTORC1-RPS6.
Brown adipose tissue (BAT) has long been recognized as an energy-consuming organ and a possible target for combating metabolism disorder. Although numerous studies have demonstrated the ability of phytochemical phenolic acids to improve obesity by activating BAT, the underlying mechanism or mechanism therein remain obscure. In this study, diet-induced obese mice, genetically obese mice, and C3H10T1/2 cells were used to examine the effects of p-Coumaric acid (CA) on metabolism profiles. The results showed that CA prevented metabolic syndromes in the two mice models through the activation of BAT. This phenomenon was closely linked to the upregulation of uncoupling protein 1 (UCP1) and the accelerated burning of fatty acids and glucose, which consequently enhanced the energy expenditure and thermogenesis. Similar results were also obtained in vitro. Importantly, these effects were mediated by the mammalian target of rapamycin complex 1 (mTORC1)-RPS6 pathway. These findings reveal, to the best of our knowledge for the first time, the close correlation between mTORC1-RPS6 and BAT-mediated thermogenesis, and, in addition, the key role played by mTORC1-RPS6 in mediating phenolic acids-induced activation of BAT, thus preventing obesity.


Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells.
Airway remodeling, as manifested by an increase in airway smooth muscle mass, mucous gland hyperplasia, and subepithelial fibrosis, contributes to the airway hyperresponsiveness and fixed obstruction seen in some asthmatic patients. Here we investigated whether the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway contributes to platelet-derived growth factor (PDGF)-stimulated mitogenesis of human airway smooth muscle cells (HASMC). PDGF treatment of quiescent HASMC resulted in the rapid tyrosine phosphorylation and DNA binding of STAT1 and STAT3. This phosphorylation was blocked by inhibition of Src and JAK2 kinases. In addition, STAT activation by PDGF was found to be redox dependent. Moreover, PDGF-induced thymidine uptake was completely blocked by pretreatment of HASMC with the STAT kinase inhibitors AG-490, SU-6656, and PP2. Interestingly, the JAK pathway was required for HASMC mitogenesis independently of mitogen-activated protein kinase activation. Inhibition of the Src and JAK kinases blocked PDGF-stimulated gene expression of the STAT target genes cyclin D1 and c-myc. These results indicate that the JAK-STAT pathway contributes to PDGF-induced mitogenesis, and thus this pathway may be important in the airway remodeling seen in some asthmatic patients.


Syphilis mimicking idiopathic intracranial hypertension.
Idiopathic intracranial hypertension (IIH) is a condition of yet unknown aetiology affecting predominantly obese females of childbearing age. IIH is a diagnosis of exclusion as raised cerebrospinal fluid pressure may occur secondary to numerous other medical conditions. An atypical phenotype or an atypical disease course should alert the physician to reevaluate a presumed IIH-diagnosis. The authors report a case of a 32-year-old non-obese male with intracranial hypertension, secondary to a syphilitic central nervous system infection, initially misdiagnosed as being idiopathic. Upon relevant antibiotic treatment, signs and symptoms of elevated intracranial pressure resolved completely. Syphilis is a rare, but very important, differential diagnosis that in this case was clinically indistinguishable from IIH.


Incidence, characteristics, and long-term follow-up of sternoclavicular injuries: An epidemiologic analysis of 92 cases.
The majority of published studies concerning sternoclavicular injuries are case series or systematic reviews. Prospective studies on the subject are hindered by the low incidence of these lesions. The aims of the present study were to provide an overview of this rare entity compared with those described in the literature and to present the long-term clinical outcome. We performed a retrospective data analysis of all sternoclavicular injuries treated at a single Level I trauma center from 1992 to 2011. Long-term clinical outcome was assessed using the ASES [American Shoulder and Elbow Surgeons], SST [Simple Shoulder Test], UCLA [University of California-Los Angeles] Shoulder Scale, and VAS [Visual Analog Scale] at latest follow-up. We detected an overall incidence of 0.9% of sternoclavicular injuries related to all shoulder-girdle lesions. Ninety-two patients (52 males and 40 females) with a mean (SD) age of 39.2 (19.5) years (median, 41 years; range, 4-92 years) were included in this study. The main trauma mechanism was fall. Classification was performed according to Allman, the time point of treatment after initial trauma, and the direction of the dislocation. Nine patients of the 15 Grade III lesions were treated conservatively by closed reduction and immobilization, while four patients were treated surgically by open reduction and internal fixation. Forty-nine percent of the patients were available for long-term follow-up at a median of 11.3 years (range, 5.3-22.6 years) with a mean ASES score of 96.21, SST score of 11.69, UCLA score of 31.89, and VAS score of 0.47. We found an overall incidence of 0.9% of sternoclavicular joint injuries related to all shoulder-girdle lesions and of 1.1% related to all dislocations, which is slightly lower compared with those described in the literature. Furthermore, we observed a high number of physeal sternoclavicular injuries with a percentage of 16% and overall good-to-excellent results at long-term follow-up. Epidemiologic study, level IV.


Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system.
A hydraulic calcium phosphate cement made of beta-tricalcium phosphate [beta-Ca3(PO4)2], monocalcium phosphate monohydrate [Ca(H2PO4)2-H2O], and water was used as a delivery system for the antibiotic gentamicin sulfate (GS). GS, added as powder or as aqueous solution, was very beneficial to the physicochemical properties of the cement. The setting time increased from 2 to 4.5 min with 3% (w/w) GS and then slowly decreased to 3.75 min with 16% (w/w) GS. The tensile strength increased from 0.4 to 1.6 MPa with 16% (w/w) GS. These effects were attributed to the presence of sulfate ions in GS. The release of GS from the cement was measured in a pH 7.4 phosphate-buffered saline solution at 37 degrees C by USP paddle method. Factors such as cement porosity, GS content and presence of sulfate ions or polymeric additives were investigated. The amount of GS released was roughly proportional to the square root of time up to approximately 50% release. Afterwards, the release rate markedly slowed down to zero. In all but two cement formulations, the total dose of GS was released within 7 days, indicating that no irreversible binding occurred between the cement paste and the antibiotic. When small amounts of hydroxypropylcellulose or poly(acrylic acid) were added to the cement, the maximum fraction released was a few percent lower than the total GS dose, suggesting some binding between the polymer and GS. The GS release rate was strongly influenced by the presence of sulfate ions in the cement paste and by the cement porosity. The higher the sulfate ion content of the cement paste, the lowe the GS release rate. This influence was attributed to the finer cement micro-structure induced by the presence of sulfate ions. Furthermore, when the initial cement porosity was increased from 38 to 69%, the release rate almost tripled (0.16 to 0.45 h-1/2). Finally, the biological activity of GS in the cement was maintained, as measured by assaying the release medium.


Caffeine versus methylphenidate and d-amphetamine in minimal brain dysfunction: a double-blind comparison.
The authors compared the efficacy of caffeine, methylphenidate, and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design. The slight improvement with caffeine was not significantly better than placebo. Both prescription drugs resulted in significant improvement and were significantly superior to caffeine. The authors suggest that the discrepancy between these results and an earlier, more optimistic report mat stem from the use in this study of pure caffeine rather than whole coffee.


Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy.
Transient elastography is a non-invasive method, for the assessment of hepatic fibrosis, developed as an alternative to liver biopsy. We studied the performance of elastography for diagnosis of fibrosis using meta-analysis. MEDLINE, EMBASE, SCI, Cochrane Library, conference abstracts books, and article references were searched. We included studies using biopsy as a reference standard, with the data necessary to calculate the true and false positive, true and false negative diagnostic results of elastography for a fibrosis stage, and with a 3-month maximum interval between tests. The quality of the studies was rated with the QUADAS tool. We identified 40 eligible studies. Summary sensitivity and specificity was 0.79 (95% CI 0.74-0.82) and 0.78 (95% CI 0.72-0.83) for F2 stage and 0.83 (95% CI 0.79-0.86) and 0.89 (95% CI 0.87-0.91) for cirrhosis. After an elastography result at/over the threshold value for F2 or cirrhosis ("positive" result), the corresponding post-test probability for their presence (if pre-test probability was 50%) was 78%, and 88% respectively, while, if values were below these thresholds ("negative" result), the post-test probability was 21% and 16%, respectively. No optimal stiffness cut-offs for individual fibrosis stages were validated in independent cohorts and cut-offs had a wide range and overlap within and between stages. Elastography theoretically has good sensitivity and specificity for cirrhosis (and less for lesser degrees of fibrosis); however, it should be cautiously applied to everyday clinical practice because there is no validation of the stiffness cut-offs for the various stages. Such validation is required before elastography is considered sufficiently accurate for non-invasive staging of fibrosis.


Arabidopsis MBF1s control leaf cell cycle and its expansion.
Multiprotein bridging factor 1 (MBF1) is known as a transcriptional co-activator that enhances transcription of its target genes by bridging between transcription factors and TATA-box-binding protein in eukaryotes. Arabidopsis thaliana has three MBF1 genes: AtMBF1a-AtMBF1c. However, details of the functions of AtMBF1 remain unclear. For this study, transgenic Arabidopsis overexpressing AtMBF1 fused to an active transcriptional repression domain (SRDX) was constructed. The chimeric protein putatively functions as a transcriptional co-repressor and as a suppressor of functions of endogenous AtMBF1 in transgenic plants. Transgenic Arabidopsis overexpressing AtMBF1-SRDX (AtMBF1-SRDX(OE)) showed an extremely small leaf phenotype under a continuous white light condition. Its leaf cells-especially those around vascular tissues, where strong expression of endogenous AtMBF1s is observed-were much smaller than those from the wild type (WT). In addition, a lower cell number was observed in leaves from AtMBF1-SRDX(OE) plants. Time course analysis of cell size revealed that cell expansion of leaves of AtMBF1-SRDX(OE) plants was dramatically suppressed during the late leaf developmental stage (cell expansion stage), when endogenous AtMBF1b is strongly expressed in the WT. The results show that ploidy levels of leaves from AtMBF1-SRDX(OE) plants were dramatically lower than those from the WT; moreover, expression levels of several negative regulators of endoreduplication were more elevated in AtMBF1s-SRDX(OE) plants than those in the WT. These observations suggest that AtMBF1-SRDX interacts with regulators of endoreduplication. Therefore, AtMBF1s are considered to affect not only leaf cell expansion but also regulation of the ploidy level in leaf cells during the leaf expansion stage.


[Asplenism and hyposplenism as an immune deficiency syndrome].
The spleen has vital immunological functions (including the clearance of pathogenic microorganisms, the synthesis of antibodies and the provision of opsonins), which cannot be completely taken over by other organs in the case of hypo- or asplenism. Deficiency or absence of splenic activity, as it occurs for instance in sickle cell anemia, in congenital asplenia or after splenectomy, consequently entails complex immunological defects, which in their turn result in an increased susceptibility to severe bacteremia. Preventive measures, such as antibiotic prophylaxis, pneumococcal vaccination and detailed instruction of the patients and their families, are recommended in order to reduce the incidence of these life-threatening infections fatal to at least 1.4% of all splenectomized children.


Classification of Alzheimer's disease progression based on sMRI using gray matter volume and lateralization index.
Note that identifying Mild Cognitive Impairment (MCI) is crucial to early detection and diagnosis of Alzheimer's disease (AD). This work explores how classification features and experimental algorithms influence classification performances on the ADNI database. Based on structural Magnetic Resonance Images (sMRI), two features including gray matter (GM) volume and lateralization index (LI) are firstly extracted through hypothesis testing. Afterward, several classifier algorithms including Random Forest (RF), Decision Tree (DT), K-Nearest Neighbor(KNN) and Support Vector Machine (SVM) with RBF kernel, Linear kernel or Polynomial kernel are established to realize binary classification among Normal Control (NC), Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI) and AD groups. The main experimental results are as follows. (1) The classification performance in the feature of LI is poor compared with those in the feature of GM volume or the combined feature of LI and GM volume, i.e., the classification accuracies in the feature of LI are relatively low and unstable for most classifier models and subject groups. (2) Comparing with the classification performances in the feature of GM volume and the combined feature of LI and GM volume, the classification accuracy of NC group versus AD group is relatively stable for different classifier models, moreover, the accuracy of AD group versus NC group is almost the highest, with the most classification accuracy of 98.0909%. (3) For different subject groups, the SVM classifier algorithm with Polynomial kernel and the KNN classifier algorithm show relatively stable and high classification accuracy, while DT classifier algorithm shows relatively unstable and lower classification accuracy. (4) Except the groups of EMCI versus LMCI and NC versus EMCI, the classification accuracies are significantly enhanced by emerging the LI into the original feature of GM volume, with the maximum accuracy increase of 5.6364%. These results indicate that various factors of subject data, feature types and experimental algorithms influence classification performances remarkably, especially the newly introduced feature of LI into the feature of GM volume is helpful to improve classification results in some certain extent.


Antioxidant status and hepatic lipid peroxidation in chloramphenicol-treated rats.
The present study reports the enzymatic and non-enzymatic antioxidant status and hepatic microsomal lipid peroxidation in chloramphenicol treated rats. Chloramphenicol at a dose of 28 mg/kg body weight orally administered to rats increased the activity of cytosolic superoxide dismutase by 63% while the activities of glutathione peroxidase and catalase were decreased by 57% and 44%, respectively. In vitro, chloramphenicol altered the activities of these enzymes though not as pronounced as the effect of the drug on the enzymes in vivo. The levels of serum vitamins A, C and beta-carotene were significantly decreased following chloramphenicol treatment. Microsomal lipid peroxidation was markedly and significantly increased by chloramphenicol treatment. The drug elicited 69% and 71% increases in the levels of malondialdehyde and lipid hydroperoxide respectively. Glutathione level and glutathione S-transferase activity were decreased by 42% and 58%, respectively, compared to untreated controls. Overall, the results of the present investigation indicate alteration of enzymatic and nonenzymatic antioxidant status and induction of lipid peroxidation by chloramphenicol. The clinical implications in the detoxification of toxic metabolites of lipid peroxidation caused by chloramphenicol warrant co-administration with antioxidant vitamins in chloramphenicol treatment regimen.


Spin gradient thermometry for ultracold atoms in optical lattices.
We demonstrate spin gradient thermometry, a new general method of measuring the temperature of ultracold atoms in optical lattices. We realize a mixture of spins separated by a magnetic field gradient. Measurement of the width of the transition layer between the two spin domains serves as a new method of thermometry which is observed to work over a broad range of lattice depths and temperatures, including in the Mott insulator regime. We demonstrate the thermometry using ultracold rubidium atoms, and suggest that interesting spin physics can be realized in this system. The lowest measured temperature is 1 nK, indicating that the system has reached the quantum regime, where insulating shells are separated by superfluid layers.


Use of pharmacokinetics in the coagulation factor treatment of patients with haemophilia.
Dosing decisions for replacement coagulation factors in patients with haemophilia should be made on an individual patient basis, with the required dose dependent on factors including the clinical situation, the severity of the factor deficiency, and the location and extent of bleeding. Moreover, there is considerable variability in the pharmacokinetics of coagulation products that needs to be considered; in particular, with both factor (F) IX and FVIII products, there is considerable inter-patient variability in in vivo recovery and terminal half-life values. In the present report, we provide a practical guide to calculating and applying pharmacokinetic parameters relevant to the optimal dosing of coagulation products. We discuss the conduct of a pharmacokinetic study in an individual patient, how to calculate pharmacokinetic values from raw data and clinical situations where an individual pharmacokinetic study is helpful. We highlight the importance of considering an individual pharmacokinetic study in all patients starting a new coagulation product.


Dynamic Stark broadening as the Dicke narrowing effect.
A very fast method to account for charged particle dynamics effects in calculations of spectral line shape emitted by plasmas is presented. This method is based on a formulation of the frequency fluctuation model (FFM), which provides an expression of the dynamic line shape as a functional of the static distribution of frequencies. Thus, the main numerical work rests on the calculation of the quasistatic Stark profile. This method for taking into account ion dynamics allows a very fast and accurate calculation of Stark broadening of atomic hydrogen high- n series emission lines. It is not limited to hydrogen spectra. Results on helium- beta and Lyman- alpha lines emitted by argon in microballoon implosion experiment conditions compared with experimental data and simulation results are also presented. The present approach reduces the computer time by more than 2 orders of magnitude as compared with the original FFM with an improvement of the calculation precision, and it opens broad possibilities for its application in spectral line-shape codes.


Surfer's ear.
Exostosis in external auditory canal is common among surfers. Common symptoms are decreased hearing or loss of hearing, ear infection, and/or plugging sensation. Repeated exposure to cold water is a key clinical history to suspect this condition. Based on symptoms and existence of infection, surgical removal of the exostosis is recommended.


Collaborative development of an electronic Personal Health Record for people with severe and enduring mental health problems.
Previous attempts to implement electronic Personal Health Records (ePHRs) underline the importance of stakeholder involvement. We describe the development of an ePHR for people with severe and enduring mental health problems, and provide a model of involving stakeholders throughout. There were three stages to the development of the ePHR. These were 1) identifying and responding to user and clinical needs; 2) preliminary testing; and 3) preliminary implementation. Stakeholder involvement was pervasive in all stages. We collaborated with 133 stakeholders in the first stage, 13 in the second, and 26 in the third. On the micro-level, a service user researcher conducted much of the data collection and analysis. On the macro-level, a service user advisory group guided decisions throughout the project, and a service user was an active member of the project executive board and the implementation team. Service users and clinicians preferred an interactive ePHR with features such as access to care plans and care notes, a mood tracker, patient reported outcomes feeding into the clinical record, and social networking features. Many of the above were constructed following consultation with the relevant professionals, however further consultation is required before building a social networking function or providing access to full care notes. Service users positively rated the usability of the ePHR. Drop-in sessions helped service users access technology and learn how to use the ePHR. We outline four considerations for future developers of ePHRs: appeal, construction, ease of use, and implementation. Success rests on implementation in routine practice, so ePHRs must be intuitive and useful for both service users and staff. Continued involvement of end users throughout the design and testing process can help to achieve this goal.


SuPreme Study: a protocol to study the neuroprotective potential of sulfate among very/extremely preterm infants.
Antenatal maternal magnesium sulfate (MgSO4) administration is a proven efficacious neuroprotective treatment reducing the risk of cerebral palsy (CP) among infants born preterm. Identification of the neuroprotective component with target plasma concentrations could lead to neonatal treatment with greater efficacy and accessibility. This is a prospective observational cohort study, in three tertiary Australian centres. Participants are preterm infants, irrespective of antenatal MgSO4 exposure, born in 2013-2020 at 24+0 to 31+6 weeks gestation, and followed up to 2 years corrected age (CA) (to September 2023). 1595 participants are required (allowing for 17% deaths/loss to follow-up) to detect a clinically significant reduction (30% relative risk reduction) in CP when sulfate concentration at 7 days of age is 1 SD above the mean.A blood sample is collected on day 7 of age for plasma sulfate and magnesium measurement. In a subset of participants multiple blood and urine samples are collected for pharmacokinetic studies, between days 1-28, and in a further subset mother/infant blood is screened for genetic variants of sulfate transporter genes.The primary outcome is CP. Surviving infants are assessed for high risk of CP at 12-14 weeks CA according to Prechtl's Method to assess General Movements. Follow-up at 2 years CA includes assessments for CP, cognitive, language and motor development, and social/behavioural difficulties.Multivariate analyses will examine the association between day 7 plasma sulfate/magnesium concentrations with adverse neurodevelopmental outcomes. A population pharmacokinetic model for sulfate in the preterm infant will be created using non-linear mixed-effects modelling. The study has been approved by Mater Misericordiae Ltd Human Research Ethics Committee (HREC/14/MHS/188). Results will be disseminated in peer-reviewed journal publications, and provided to the funding bodies. Using consumer input, a summary will be prepared for participants and consumer groups.


Outcomes of 50 Patients With Ewing Sarcoma Family of Tumors Treated at a Single Institution in Taiwan.
To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT.


Complications Associated with Microdebriders in Otolaryngology Procedures from 2011 to 2021: A MAUDE Study.
The microdebrider is a powered surgical instrument that is widely used in the field of otolaryngology. We aim to identify the type and frequency of device malfunctions, patient complications, and subsequent interventions related to the use of microdebriders. Cross-sectional analysis. The US Food and Drug Administration (FDA) 2011 to 2021 Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was queried for reports of "microdebrider," with adverse events selected that pertained to usage in head and neck surgeries from January 1, 2011 to December 31, 2021. There were 282 adverse events in 267 individual medical device reports (MDR). Although the majority of the reports did not specify the specific operation, endoscopic sinus surgery was the most common reported procedure (89, 33.3%). The most common cause of device malfunction was due to a broken piece (120, 48.2%) followed by overheating of the microdebrider motor (78, 31.3%). Of the reports which specified patient injury, the most commonly reported was "unintentional tissue damage," (10, 32.3%). The microdebrider has demonstrated utility within the field of otolaryngology, but is not without risk of malfunction that can cause patient injury. By understanding possible risks of microdebrider usage, including tissue damage, burns, and bleeds caused by device malfunction or operator error, physicians can be better prepared to address complications and educate patients.


[The treatment of benign lesions of the cervix by infrared coagulation (author's transl)].
The infra-red coagulation is a new outpatient method for the treatment of benign changes in gynaecology. It causes little pain and is suitable for haemostasis at the cervix, in the vagina and in the vulva. The effect of this treatment is comparable to laser coagulation. An exact dosage of the coagulation energy is possible and therefore the depth of treatment and the surface of the treatment are known accurately. The side effects of the treatment are minimal, a fast and good healing of the coagulation area can be expected. The results of infra-red coagulation in 72 patients are presented.


Real-time monitoring of stain formation and removal on calcium hydroxyapatite surfaces using quartz crystal sensor technology.
Stain formation, stain inhibition and stain removal may be monitored in real-time using a novel method employing a quartz crystal resonance sensor (QCR), based upon quartz crystal microbalance (QCM) technologies. Crystalline hydroxyapatite (HA) surfaces were prepared on phosphate-terminated, polymer-modified gold surfaces of quartz crystal transducers. The resulting sensors were placed in a specially constructed flow cell, and the interaction of adsorbates from the tea stain solution monitored as a function of time. The ability of sodium tripolyphosphate (STP) to remove extrinsic stain and also to inhibit its formation was examined. The adsorption of material from the staining solution passed over the sensor was clearly observable, and once bound, the crystal based real-time data suggest that tea adsorbates were not removed in the absence of an active under conditions of continuous flow. STP was shown to rapidly remove existing stain, and exhibited a clear inhibitory action on stain formation irrespective of whether the HA had been previously exposed to tea chromogens. The continuous data generated by the QCR technique were in good agreement with the results obtained using a discontinuous spectrophotometric method. The presently described quartz crystal model for extrinsic dental stain should provide a valuable tool to aid understanding of the interactions of staining agents with a crystalline HA surface as a model tooth surface, and to evaluate the efficacy and mode of action of STP and putative stain removal agents.


Effects of Guanxinning injection on rat cytochrome P450 isoforms activities in vivo and in vitro.
1. We aimed to investigate the regulatory effects of Guanxinning injection (GXNI) on activities of cytochrome P1A2 (CYP1A2), CYP2C11, CYP2D1 and CYP3A1/2 by probe drugs in rats in vivo and in vitro. 2. GXNI-treated and blank control groups were administered GXNI and physiological saline by caudal vein for 14 days consecutively, then they were given the probe drugs of caffeine (10 mg/kg), tolbutamide (10 mg/kg), metoprolol (20 mg/kg) and dapsone (10 mg/kg) by intraperitoneal injection. The blood samples were collected at different times for ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Changes of the pharmacokinetics parameters between the GXNI-treated and the blank control groups were used to evaluate the effects of GXNI on the four CYP450 isoforms in rats in vivo. After blood collection, the livers of rats were taken and made microsomes for in vitro tests. The relevant metabolites of phenacetin, tolbutamide, dextromethorphan and testosterone were analyzed quantitatively by high-performance liquid chromatography (HPLC) after microsome incubation. The statistical differences between the two groups were observed to detect the effects of GXNI on the four CYP450 isoforms in rats in vitro. 3. The in vivo and in vitro results demonstrated that GXNI could induce CYP1A2 activity in rats, but had no significant effects on CYP2C11, CYP2D1 and CYP3A1/2.


Improving outcomes of hospitalized patients: the Physician Relationships, Improvising, and Sensemaking intervention protocol.
Our goal is to improve the safety and effectiveness of inpatient care. Rather than focus on improving process of care, we focus on the social structure within physician teams. We have developed the Physician Relationships, Improvising, and Sensemaking (PRISm) intervention to improve the way physician teams round, enabling them to better relate, make sense of their patients' conditions, and improvise in uncertain clinical situations. We are currently studying the impact of PRISm on adverse events and complications in hospitalized patients. This manuscript describes the PRISm intervention. PRISm is a structured communication tool consisting of three components: daily briefings before rounds; use of the Situation, Task, Intent, Concern, and Calibrate (STICC) framework during rounds as part of the discussion of individual patients; and debriefings after rounds. We are implementing the PRISm intervention on eight inpatient medical and surgical physician teams in the South Texas Veterans Health Care System. We are assessing PRISm impact on the way team members relate to each other, round, and discuss patients through pre- and post-implementation observations and surveys. We are also assessing PRISm impact on complications and adverse events. Finally, we are interviewing physicians regarding their experience using the intervention. Our results will allow us to begin to understand the potential impact of interventions designed to improve how providers relate to each other, improvise, and make sense of what is happening as a strategy for improving inpatient care. Our in-depth data collection will enable us to assess how relationships, improvising, and sensemaking influence patient outcomes, potentially through creating shared mental models or enhancing distributed cognition during clinical reasoning. Finally, our results will lay the groundwork for larger implementation studies to improve clinical outcomes through improving how providers, and providers, patients, and caregivers, relate.


[Cell division as the determining factor in the index of the proliferative level of cultured cells].
Theoretical substantiation of dynamics of cultured cell average size as a basis for the index of rate of their proliferative activity in population is presented. Mathematic formula deduced by the author for this index is described. Some examples for its use are given and the name for the index is proposed.


A sheep in wolf's clothing?
A 25-year-old college student with no medical history sought care at our hospital for a nonproductive cough, subjective fevers, myalgia, and malaise that he'd developed 10 days earlier. The day before his visit, he'd also developed scratchy red eyes and a sore throat. He said he'd taken an over-the-counter cough suppressant to help with the cough, but his eyes and lips developed further redness and irritation. On examination, the patient demonstrated conjunctival suffusion, periorbital edema, diffuse oral stomatitis with pseudomembranous crusting, and nasal crusting. His vital signs were within normal limits, and he had no epithelial skin eruptions or erosions in any other mucosal regions. What's your diagnosis?


Localization of membrane-associated (NiFe) and (NiFeSe) hydrogenases of Desulfovibrio vulgaris using immunoelectron microscopic procedures.
The intracellular location of membrane-associated (NiFe) and (NiFeSe) hydrogenases of Desulfovibrio vulgaris was determined using pre-embedding and post-embedding immunoelectron microscopic procedures. Polyclonal antisera directed against the purified (NiFe) and (NiFeSe) hydrogenases were raised in rabbits. One-day-old cultures of D. vulgaris, grown on a lactate/sulfate medium, were used for all experiments in these studies. For post-embedding labeling studies cells were fixed with 0.2% glutaraldehyde and 0.3% formaldehyde, dehydrated with methanol, and embedded in the low-temperature resin Lowicryl K4M. Our post-embedding studies using antibody-gold or protein-A-gold as electron-dense markers revealed the location of the two hydrogenases exclusively at the cell periphery; the precise membrane location was then demonstrated by pre-embedding labeling. Spheroplasts were incubated with the polyclonal antisera against (NiFe) and (NiFeSe) hydrogenase followed by ferritin-linked secondary antibodies prior to embedding and sectioning. The observed labeling pattern unequivocally revealed that the antigenic reactive sites of the (NiFe) hydrogenase are located in the near vicinity of the cytoplasmic membrane facing into the periplasmic space, whereas the (NiFeSe) hydrogenase is associated with the cytoplasmic side of the cytoplasmic membrane.


Management of abdominal aortic aneurysms in the UK.
Outcomes of abdominal aortic aneurysm repair are improving in the UK, at least in part as a result of vascular specialization, the reconfiguration of services to dedicated vascular centres and the advent of the national screening programme.


The incidence and pattern of knee injury associated with dislocation of the hip.
A retrospective survey of 135 posterior dislocations and fracture-dislocations of the hip was carried out in order to define the pattern of associated knee injuries. Thirty-five patients had sustained a significant injury to the knee, of which twenty-five were clearly attributable to a direct blow on the front of the knee (fractured patella, traumatic chondromalacia, fractures of femoral and tibial condyles) and ten were compatible with valgus, varus or rotational forces (medial, lateral and cruciate ligament tears). The second type of injury has not been widely recognised but it is important that it should not be overlooked.


Facilitating communication among speech pathologists treating children with cleft palate.
An interactive web-based system was designed to facilitate communication between nonspecialist speech pathologists who provide therapy for individuals with speech disorders associated with cleft palate or craniofacial anomalies and specialist speech pathologists who provide physiologically based assessments of speech production. The web site includes instructional presentations, streaming video clips of endoscopic examinations, and exchange of information about the nature of therapy as recommended by the specialist and as provided by the nonspecialist. The approach demonstrates use of web-based computer facilities to improve the quality of communication among professionals with the goal of improving the outcomes of speech therapy. Information from the site can also be used in academic training programs as a teaching tool in courses on cleft palate speech.


Pressure wave generated by the passage of a heavy charged particle in water.
Energy deposition around the trajectories of ionizing particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns in water and subsequent diffusion of deposited heat is calculated using computational fluid dynamics. Immediately after the deposition of energy by the charged particle, the temperature and pressure in the vicinity of the particle track both increase dramatically, leading to the formation of a thermal spike and a pressure wave. Initially, the region of heat deposition is primarily localized to a region called the "thermal core," which has dimensions of 0.3, 1, and 3 nm for particles with LETs of 4, 40, and 400 keV/microns, respectively. Instantaneous peak temperatures within the thermal core were 800 degrees C-2000 degrees C and peak pressures were about 25,000 atm. This sudden deposition of heat in a localized region leads to a very strong shock wave around the particle trajectory, which is shown to last for a duration of 10(-9)-10(-8) s. Even at distances beyond 10 nm away from the particle trajectory, pressures above 100 atm could exist for a duration of up to 10(-11) s. This local and transient environment, created by the passage of a charged particle in a medium, may lead to new mechanisms of radiation action leading to cell damage, as well as to the development of new radiation detectors.


Stability of superfluid and supersolid phases of dipolar bosons in optical lattices.
We perform a stability analysis of superfluid (SF) and supersolid (SS) phases of polarized dipolar bosons in two-dimensional optical lattices at high filling factors and zero temperature, and obtain the phase boundaries between SF, checkerboard SS (CSS), striped SS (SSS), and collapse. We show that the phase diagram can be explored through the application of an external field and the tuning of its direction with respect to the optical lattice plane. In particular, we find a transition between the CSS and SSS phases.


A facile synthesis of novel near-infrared pyrrolopyrrole aza-BODIPY luminogens with aggregation-enhanced emission characteristics.
Here we report the facile synthesis of two triphenylethylene-modified pyrrolopyrrole aza-BODIPY dyes with an aggregation-enhanced emission feature. NIR-emitting nanoparticles with remarkable photostability properties and applications in bioimaging were generated due to their good dispersity in water and biocompatibility.


Divergent Stereoselectivity in Phosphothreonine (pThr)-Catalyzed Reductive Aminations of 3-Amidocyclohexanones.
Phosphothreonine (pThr)-embedded peptide catalysts are found to mediate the reductive amination of 3-amidocyclohexanones with divergent selectivity. The choice of peptide sequence can be used to alter the diastereoselectivity to favor either the cis-product or trans-product, which are obtained in up to 93:7 er. NMR studies and DFT calculations are reported and indicate that both pathways rely on secondary interactions between substrate and catalyst to achieve selectivity. Furthermore, catalysts appear to accomplish a parallel kinetic resolution of the substrates. The facility for phosphopeptides to tune reactivity and access multiple products in reductive aminations may translate to the diversification of complex substrates, such as natural products, at numerous reactive sites.


Activities and participation after stroke: validity and reliability of the Turkish version of IMPACT-S questionnaire.
Objective: This study aims to translate the screener part of the The International Classification of Functioning, Disability and Health (ICF) Measure of Participation and ACTivities Questionnaire (IMPACT-S) into Turkish and to test its reliability and validity in Turkish patients with stroke.Materials and methods: Participants were recruited from the inpatient rehabilitation clinic of a university hospital. Eighty-six stroke patients (mean ages: 60.43 ± 12.62 years; range 20-82 years; 51 males and 35 females) were included in the study. Demographic properties of the patients (age, sex, education, occupation, and body mass index), the start of in-patient rehabilitation treatment, affected extremity, types of stroke, and comorbidities were recorded. After that IMPACT-S questionnaire and World Health Organization Disability Assessment Schedule-II (WHODAS-II) were used for data collection. A test-retest interval of 7 d was used to assess the reliability. Internal consistency between the items was assessed by Cronbach's alpha coefficient. For reliability; test-retest reliability, intraclass correlation coefficient (ICC), paired sample t-test were used. Intercorrelation of variables was performed with Spearman's rho tests.Results: Totally 86 patients completed test/retest procedures. Cronbach's alpha coefficient of the questionnaire was found to be 0.96. Both internal consistency (Cronbach's alpha score range: 0.65-0.98) and test-retest reliability (ICC values range: 0.86-0.97) of the IMPACT-S were found to be good. The correlations between all IMPACT-S subscales were moderate to strong (correlation range: 0.45-0.80). The correlation between the Activities and Participation scores (0.86) and IMPACT-S total score (0.96) were very strong. Statistically significant negative correlations were detected between all sub-scores of IMPACT-S and WHODAS-II, except for life activities/communication and life activities/knowledge. These findings show excellent concurrent validity. However, a lower-than-expected correlation between Major life areas (IMPACT-S) and Life activities (WHODAS-II) was observed.Conclusion: The Turkish version of the IMPACT-S is a valid and reliable questionnaire for evaluating activities and participation in patients with stroke.Implications for rehabilitationPatients with stroke experience difficulties across multiple participation domains, such as major life areas and community life.The screener part of the IMpact on Participation and ACTivities (IMPACT-S) questionnaire is the only measure that accurately reflects The International Classification of Functioning, Disability and Health (ICF) sections and appears a promising outcome measure in rehabilitation research.The Turkish version of the IMPACT-S was found to be valid and reliable for evaluating "Activities and Participation" in stroke patients.


Model-Based Evaluation of Exenatide Effects on the QT Interval in Healthy Subjects Following Continuous IV Infusion.
Investigation of the cardiovascular proarrhythmic potential of a new chemical entity is now an integral part of drug development. Studies suggest that meals and glycemic changes can influence QT intervals, and a semimechanistic model has been developed that incorporates the effects of changes in glucose concentrations on heart rate (HR) and QT intervals. This analysis aimed to adapt the glucose-HR-QT model to incorporate the effects of exenatide, a drug that reduces postprandial increases in glucose concentrations. The final model includes stimulatory drug effects on glucose elimination and HR perturbations. The targeted and constant exenatide plasma concentrations (>200 pg/mL), via intravenous infusions at multiple dose levels, resulted in significant inhibition of glucose concentrations. The exenatide concentration associated with 50% of the stimulation of HR production was 584 pg/mL. After accounting for exenatide effects on glucose and HR, no additional drug effects were required to explain observed changes in the QT interval. Resulting glucose, HR, and QT profiles at all exenatide concentrations were adequately described. For therapeutic agents that alter glycemic conditions, particularly those that alter postprandial glucose, the QT interval cannot be directly compared to that with placebo without first accounting for confounding factors (eg, glucose) either through mathematical modeling or careful consideration of mealtime placement in the study design.


Anxiety in children following hospitalization: a proposal for a nursing diagnosis.
to describe the process of developing a nursing diagnosis regarding child anxiety following hospitalization, which is to be submitted to the international classification for nursing practice, in accordance with the guidelines set out by the International Council of Nurses and the ISO standard 18104:2014. this methodological study includes a conceptual analysis that bases itself on analyzing the phenomena of anxiety and hospitalization, while identifying the critical attributes of the concept and developing an operational definition. all the criteria for including a new nursing concept were followed and there was no violation of the framework of the International Classification for Nursing Practice with the proposed inclusion, since the concept of anxiety already exists in this classification system and the concept of anxiety from hospitalization would be considered a species or subclass of this concept. this analysis of the concept of hospitalization anxiety in children allowed its meaning to be clarified and, consequently, understanding to be constructed regarding its practical applicability. This achievement contributed in terms of providing incentive to develop new proposals for nursing diagnoses to be included in the International Classification for Nursing Practice.


Parametric oscillations in a whispering gallery resonator.
We demonstrate strongly nondegenerate optical continuous-wave parametric oscillations in crystalline whispering gallery mode resonators fabricated from LiNbO3. The required phase matching is achieved by geometrical confinement of the modes in the resonator.


Varicella vaccination in children with atopic eczema.
Chickenpox in children may be complicated by local or systemic bacterial infections. Group A streptococci and S. aureus are the predominant pathogens. Children with atopic dermatitis are particularly prone to bacterial superinfection. After the introduction of universal varicella vaccination in the USA ten years ago, the number of serious bacterial soft tissue infections in children dropped significantly. Since 2004, the VZV immunization has also been included in the routine German series.Many children with atopic dermatitis have not been immunized because of concerns on the part of parents or physicians. Recent studies demonstrated the safety and efficacy of VZV vaccination in children with atopic dermatitis who appear to benefit particularly from this vaccination.


Cell death as a trigger for morphogenesis.
The complex morphologies observed in many biofilms play a critical role in the survival of these microbial communities. Recently, the formation of wrinkles has been the focus of many studies aimed at finding fundamental information on morphogenesis during development. While the underlying genetic mechanisms of wrinkling are not well-understood, recent discoveries have led to the counterintuitive idea that wrinkle formation is triggered by localized cell death. This work examines the hypothesis that the material properties of a biofilm both power and control wrinkle formation within biofilms in response to localized cell death. Using an agent-based model and a high-performance platform (Biocellion), we built a model that qualitatively reproduced wrinkle formation in biofilms due to cell death. Through the use of computational simulations, we determined important relationships between cellular level mechanical interactions and changes in colony morphology. These simulations were also used to identify significant cellular interactions that are required for wrinkle formation. These results are a first step towards more comprehensive models that, in combination with experimental observations, will improve our understanding of the morphological development of bacterial biofilms.


Wolbachia spread dynamics in stochastic environments.
Dengue fever is a mosquito-borne viral disease with 100 million people infected annually. A novel strategy for dengue control uses the bacterium Wolbachia to invade dengue vector Aedes mosquitoes. As the impact of environmental heterogeneity on Wolbachia spread dynamics in natural areas has been rarely quantified, we develop a model of differential equations for which the environmental conditions switch randomly between two regimes. We find some striking phenomena that random regime transitions could drive Wolbachia to extinction from certain initial states confirmed Wolbachia fixation in homogeneous environments, and mosquito releasing facilitates Wolbachia invasion more effectively when the regimes transit frequently. By superimposing the phase spaces of the ODE systems defined in each regime, we identify the threshold curves below which Wolbachia invades the whole population, which extends the theory of threshold infection frequency to stochastic environments.


Portal hypertension: surgical management in the 1990s.
Although liver transplantation offers definitive treatment for portal hypertension with end-stage liver failure, surgical portosystemic shunts avoid the risks of transplantation and immunosuppressive therapy, and transjugular intrahepatic portosystemic shunt (TIPS) creates a portosystemic shunt with minimal operative risk. The appropriate applications of these modalities are discussed. All adults undergoing primary liver transplantation alone (PLT, n = 265), PLT after TIPS (n = 34), PLT after surgical shunts (n = 12), surgical shunt alone (n = 13), TIPS alone (n = 35), or surgical shunt after PLT (n = 5) served as the basis of this study. In contrast to surgical shunts before PLT, TIPS before PLT increased the 1-year graft survival. Surgical shunts alone were done in 18 patients with normal or near normal liver function with 100% survival. TIPS alone offered effective symptomatic relief to most patients, all of whom were judged not to be surgical candidates. TIPS, surgical shunts, and liver transplantation each have a logical role in management of portal hypertension. Surgical candidates with Child's B or C liver failure should be treated with liver transplantation, and TIPS offers effective treatment for nonsurgical candidates. Surgical shunts can be performed with excellent results in patients with Child's A liver disease. Portal vein occlusion with normal liver function can be successfully treated with surgical shunts.


Vision Quality Questionnaire Assessment in Patients After Topography-Guided Photorefractive Keratectomy for Irregular Astigmatism Secondary to Radial Keratotomy.
To evaluate the vision-related quality of life with the National Eye Institute Refractive Error Quality of Life (NEI-RQL) questionnaire in patients with astigmatism secondary to radial keratotomy surgery who underwent topography-guided photorefractive keratectomy. Prospective non-randomized clinical trial. This study included 15 patients (30 eyes) aged > 21 years, mean age 55.1 (SD, 3.5) years, 53.3% female, with astigmatism ≤ - 6.00 D resulting from radial keratotomy, which could have been associated with hyperopia ≤ + 6.00 D. Photorefractive keratectomy with topography-guided custom ablation treatment was used in all cases. The patients answered the NEI-RQL questionnaire preoperatively and at 4 and 48 months after topography-guided photorefractive keratectomy. The following data were collected: age, sex and education level, pre-operative refraction data, visual acuity with or without correction, pachymetry, and keratometry. There was a significant difference between pre-and postoperative NEI-RQL scores for the domains clarity of vision, near vision, far vision, diurnal fluctuation, activity limitations, glare, symptoms, correction dependence, appearance, and satisfaction with correction (p < 0.001). Topography-guided photorefractive keratectomy improved vision-related quality of life in patients with a history of irregular astigmatism secondary to radial keratotomy.


SIRT3-Mediated Dimerization of IDH2 Directs Cancer Cell Metabolism and Tumor Growth.
The isocitrate dehydrogenase IDH2 produces α-ketoglutarate by oxidizing isocitrate, linking glucose metabolism to oxidative phosphorylation. In this study, we report that loss of SIRT3 increases acetylation of IDH2 at lysine 413 (IDH2-K413-Ac), thereby decreasing its enzymatic activity by reducing IDH2 dimer formation. Expressing a genetic acetylation mimetic IDH2 mutant (IDH2K413Q) in cancer cells decreased IDH2 dimerization and enzymatic activity and increased cellular reactive oxygen species and glycolysis, suggesting a shift in mitochondrial metabolism. Concurrently, overexpression of IDH2K413Q promoted cell transformation and tumorigenesis in nude mice, resulting in a tumor-permissive phenotype. IHC staining showed that IDH2 acetylation was elevated in high-risk luminal B patients relative to low-risk luminal A patients. Overall, these results suggest a potential relationship between SIRT3 enzymatic activity, IDH2-K413 acetylation-determined dimerization, and a cancer-permissive phenotype. Cancer Res; 77(15); 3990-9. ©2017 AACR.


Lessons in liability for pediatric nurses.
Education on the legal aspects of pediatric nursing practice can help nurses develop a proactive approach to prevent patient injury and subsequent legal liability. This is an important area of professional practice because the risk of malpractice liability is often greater with the pediatric population. Children's unique health care problems, limited ability to communicate their needs, and physiological immaturity increase liability risks. This article uses a case study approach to identify specific pediatric liability risks and nursing literature to formulate strategies that pediatric nurses can use to limit their liability.


Restraint Reduction, Restraint Elimination, and Best Practice: Role of the Clinical Nurse Specialist in Patient Safety.
Baseline restraint prevalence for surgical step-down unit was 5.08%, and for surgical intensive care unit, it was 25.93%, greater than the National Database of Nursing Quality Indicators (NDNQI) mean. Project goal was sustained restraint reduction below the NDNQI mean and maintaining patient safety. Soft wrist restraints are utilized for falls reduction and preventing device removal but are not universally effective and may put patients at risk of injury. Decreasing use of restrictive devices enhances patient safety and decreases risk of injury. Phase 1 consisted of advanced practice nurse-facilitated restraint rounds on each restrained patient including multidisciplinary assessment and critical thinking with bedside clinicians including reevaluation for treatable causes of agitation and restraint indications. Phase 2 evaluated less restrictive mitts, padded belts, and elbow splint devices. Following a 4-month trial, phase 3 expanded the restraint initiative including critical care requiring education and collaboration among advanced practice nurses, physician team members, and nurse champions. Phase 1 decreased surgical step-down unit restraint prevalence from 5.08% to 3.57%. Phase 2 decreased restraint prevalence from 3.57% to 1.67%, less than the NDNQI mean. Phase 3 expansion in surgical intensive care units resulted in wrist restraint prevalence from 18.19% to 7.12% within the first year, maintained less than the NDNQI benchmarks while preserving patient safety. The initiative produced sustained reduction in acute/critical care well below the NDNQI mean without corresponding increase in patient medical device removal. By managing causes of agitation, need for restraints is decreased, protecting patients from injury and increasing patient satisfaction. Follow-up research may explore patient experiences with and without restrictive device use.


[Mechanism of Calculus Bovis Sativus in inhibiting hepatocyte lipid deposition based on serum pharmacology].
The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.


Overexpression of HDJ-2 protects astrocytes from ischemia-like injury and reduces redistribution of ubiquitin staining in vitro.
HDJ-2, a member of the HSP40 family, functions as a cochaperone to promote protein folding both by binding to unfolded polypeptides and by regulating the activity of HSP70. This study tested whether HDJ-2 overexpression alone could provide significant protection from ischemia-like injury. Primary mouse astrocyte cultures were infected with an HDJ-2 encoding retroviral vector or control retrovirus lacking HDJ-2. Expression of HDJ-2 was confirmed by immunohistochemical staining and immunoblotting. Injury paradigms to mimic ischemia were glucose deprivation (GD) for 24 hours and oxygen-glucose deprivation (OGD) for 8 hours. Cell death was determined by trypan blue exclusion and cell counting. Overexpression of HDJ-2 alone significantly reduced astrocyte injury after both GD and OGD, independent of an elevation in HSP70. To further search for the mechanism of HDJ-2 protection, cultured astrocytes allowed to recover 16 hours after 8 hours GD were labeled with a monoclonal antiubiquitin antibody that recognizes both free ubiquitin and ubiquitinated proteins. The immunolabeling pattern changed from a relatively even distribution in both nuclei and cytoplasm in control cells to heterogeneous aggregates and marked reduction of nuclear staining in most of the cells after GD. When HDJ-2 was overexpressed, the number of cells with evidence of protein aggregation was significantly reduced. Thus, blocking protein aggregation may be an important mechanism by which HDJ-2 protects cells from damage.


Growth and properties of aligned ZnO nanowires and their applications to n-ZnO/p-Si heterojunction diodes.
Aligned n-ZnO nanowires were synthesized via simple thermal evaporation process by using metallic zinc powder in the presence of oxygen on p-silicon (Si) substrate. The as-synthesized aligned ZnO nanowires were characterized in terms of their structural and optical properties by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction process (XRD) and room-temperature photoluminescence (PL) properties. The detailed structural and optical studies revealed that the as-grown nanowires are single crystalline with the wurtzite hexagonal phase and exhibit good optical properties. From application point of view, the as-grown aligned n-ZnO nanowires on p-Si substrates were used to fabricate heterojunction diodes. The fabricated heterojunction diodes exhibited good electrical (I-V) properties with the turn-on voltage of approximately 1.0 V. A temperature-dependant (from 25 degrees C approximately 130 degrees C), I-V characteristics for the fabricated device was also demonstrated in this paper. The presented results demonstrate that the simply grown aligned n-ZnO nanowires on p-Si substrate can be efficiently used for the fabrication of efficient heterojunction devices.


The Puerto Rican parrot reintroduction program: sustainable management of the aviary population.
The cornerstone of the recovery plan for the critically endangered Puerto Rican parrot (Amazona vitatta) is an actively managed, long-term reintroduction program. One captive population distributed across two aviaries in Puerto Rico is the sole source for release but its ability to persist as a managed resource has not been evaluated since 1989. We conducted an assessment for sustainable management of the aviary population while harvesting for release. To assess demographic rates such as population growth, vital rates, and age/sex structure, we compiled a studbook database on all living, dead, and released individuals in the aviary population. Using an individual-based risk assessment model we applied population specific data based on the management period from 1993 to 2012 to simulate future aviary population dynamics and evaluate future potential production. We modeled four potential management strategies to harvest parrots for proposed releases; these scenarios vary the number of parrots and the life stage. Our simulations revealed that the aviary population can be simultaneously managed for sustainability and harvesting of parrots for release. However, without cautious management, overharvesting can jeopardize sustainability of the aviary population. Our analysis of the aviary breeding program provides a rare opportunity to review progress relative to conservation program objectives after four decades of active management. The successful growth of the aviary population and its ability to serve as a sustainable source for reintroductions supports the 1973 decision to build a breeding program from a small population of 13 parrots.


Membrane currents of the tunicate egg under the voltage-clamp condition.
1. Ionic currents of the egg membrane of a certain tunicate. Halocynthia roretzi Drashe, were studied by the voltage-clamp technique. 2. The membrane depolarization beyond -55mV in standard artificial sea water induced mainly transient inward current and slight outward currents, when the holding potential was kept at -99 mV. 3. The transient inward current was composed of two components; the major one showed a faster time course, a more negative critical level of about -55 mV, and a reversal potential around +60 mV and the minor one showed a slower time course, a less negative critical level o -10 mV, and no definite reversal potential. 4. The major component became maximum at about -25 mV with the peak time of 6-9 msec at 15 degrees C, and the maximum currents ranged from 0-5 to 1-5 X 10(-5) A/cm2. 5. The major component of the inward current was abolished by the replacement of Na with choline or Tris or Cs ions, while it was almost unaltered by the replacement with Li. The minor component was independent of Na concentration in the external solution. 6. The major component showed the activation and inactivation identical with those of Na current of other excitable membranes. A conditioning depolarization over -90 mV inactivated the Na current and the half inactivation of the major inward current was obtained by a conditioning pulse to -56 mV, when the pulse duration was 400 msec and the temperature was at 15 degrees C. 7. The time course of the Na current was formulated with m and h parameters in the following equations: (see article). 8. The kinetic parameters taum and tauh of egg Na current were calculated and compared with those of the squid axon. The potential dependence of taum and tauh was almost identical with that of the axon, but the absolute values of both taum and tauh were ten- to twentyfold larger than those of the axon in any range of the membrane potential. 9. The temperature depdence of the kinetic parameters taum, tauh and of the chord conductance gNa was studied. The Q10's for taum and tauh were both 4-0, while the Q10 for gNa was 2-0 in the temperature range from 5 to 20 degrees C. 10. The outward and inward rectifying conductances of egg membrane were remarkably activated at the potential level above +100 mV and below -70 mV respectively in standard artificial sea water. Both increased currents were subsequently subject to inactivation. 11. It was suggested that Na, Ca, K inward rectifying and K outward rectifying conductances all exist separately in the egg cell membrane and the Na current was essentially identical with that through the Na channel in other excitable membranes.


Passage of molecules through the wall of the gastrointestinal tract. Urinary recovery of different-sized polyethylene glycols after intravenous and intestinal deposition.
The urinary recovery of different-sized (282-1206 dalton) polyethylene glycols (PEGs) after intravenous administration was determined. Mixtures of different-sized PEGs were injected intravenously in anesthetized pigs, and the urinary recovery at different times was determined by means of reversed-phase high-performance liquid chromatography. PEGs in the 722-1206-dalton range were all recovered to the same extent, whereas the recovery of PEGs in the 282-678-dalton range was related to molecular size; that is, the smaller the molecule, the less the urinary recovery. Moreover, less was found of the 370-414-dalton PEGs than of the 678-722-dalton PEGs in the blood after intravenous injection. These findings have a bearing on the measurements of intestinal permeability to different-sized PEGs, in which absorption-molecular weight profiles are assessed by urinary recovery after oral load. Thus, if PEGs in the 282-678-dalton range are used for such measurements, the absorption-molecular weight profile should be corrected for non-intestinal, size-dependent filtration.


Oral Manifestations of Chronic Kidney Disease and Renal Secondary Hyperparathyroidism: A Comparative Review.
Recent epidemiological studies have demonstrated that significant associations exist between oral disease and diseases involving non-oral tissues. Occasionally, the roles may be reversed and the oral cavity can be severely affected by systemic disease originating in another part of the body. Renal secondary hyperparathyroidism is a common endocrinopathy that occurs as a consequence of chronic azotemic kidney disease. Renal osteodystrophy, the most dramatic clinical consequence of renal secondary hyperparathyroidism is uncommon, but can result in demineralization of maxillofacial bones, loosening of teeth, and pathological jaw fractures. The purpose of this report is to update the current understanding of the pathophysiology of this endocrine disease and to compare the oral manifestations of renal secondary hyperparathyroidism in humans and companion animals. A 50-year review of the veterinary literature was undertaken to examine the clinical presentation of renal osteodystrophy in dogs, and to determine what clinical consequences of renal secondary hyperparathyroidism have been reported in domestic cats.