Spacetime representation of global electrocortical activity.
A model for global electrocortical activity is developed by considering telencephalonic structures as mass of linked oscillators generating activity with a number of resonant modes. Equations for the signals are written in the comoving frame and then transformed into the laboratory frame. The state transition matrix is obtained in the presence of electric and magnetic fields.


Initiating pain and palliative care outpatient services for the suburban underserved in Montgomery County, Maryland: Lessons learned at the NIH Clinical Center and MobileMed.
With the ongoing expansion of palliative care services throughout the United States, meeting the needs of socioeconomically marginalized populations, as in all domains of healthcare, continues to be a challenge. Our specific aim here was to help meet some of these needs through expanding delivery of pain and palliative care services by establishing a new clinic for underserved patients and collecting descriptive data about its operation. In November of 2014, the National Institutes of Health Clinical Center's Pain and Palliative Care Service (PPCS) launched a bimonthly offsite pain and palliative care outpatient clinic in collaboration with Mobile Medical Care Inc. (MobileMed), a private not-for-profit primary care provider in Montgomery County, Maryland, serving underserved area residents since 1968. Staffed by NIH hospice and palliative medicine clinical fellows and faculty, the clinic provides specialty pain and palliative care consultation services to patients referred by their primary care healthcare providers. A patient log was maintained, charts reviewed, and referring providers surveyed on their satisfaction with the service. The clinic had 27 patient encounters with 10 patients (6 males, 4 females, aged 23-67) during its first 7 months of operation. The reason for referral for all but one patient was chronic pain of multiple etiologies. Patients had numerous psychosocial stressors and comorbidities. All primary care providers who returned surveys (n = 4) rated their level of satisfaction with the consultation service as "very satisfied" or "extremely satisfied." This brief descriptive report outlines the steps taken and logistical issues addressed to launch and continue the clinic, the characteristics of patients treated, and the results of quality-improvement projects. Lessons learned are highlighted and future directions suggested for the clinic and others that may come along like it.


Participation in Physical Activity at Time of Presentation to a Specialty Concussion Clinic Is Associated With Shorter Time to Recovery.
Novel research suggests that children engaging in physical activity during recovery from concussion may recover more rapidly. To determine if level of physical activity at presentation to a rehabilitation-based concussion specialty clinic predicted days from injury to recovery. Retrospective cohort. A concussion sub-specialty clinic at an academic institution. Retrospective review of medical records between September 2015 and February 2017 identified 178 children ages 6-17 years (mean age = 13.7 years; standard deviation [SD] = 2.7 years) who presented within 60 days of concussion and were ultimately deemed recovered and cleared to progress to full return to high-risk activities. Not applicable. Physical activity at initial visit was classified as none-to-light (79%) versus moderate-to-heavy (21%). A doubly robust, inverse probability of exposure weighted linear regression model was used to examine the relationship between physical activity level and days to recovery, while adjusting for 10 demographic and clinical variables. Children participating in moderate-to-heavy activity at initial evaluation in concussion clinic averaged recovery 21 days quicker (95% confidence interval [CI] -27.1, -15.5, P < .001) than children who were engaging in none-to-light activity. This finding did not change when removing children who were deemed recovered at the first visit (who may have initiated physical activity after becoming asymptomatic). These data add to growing evidence that progressive physical activity during recovery from concussion does not appear to be harmful. Physical activity represents a modifiable variable in recovery, and physicians can potentially expedite symptomatic recovery by recommending noncontact physical activity as tolerated during concussion recovery.


A simplified approach to the treatment of hypertension.
A new beta-adrenoreceptor blocking drug (timolol) was used in two clinical studies. In the first double blind study administration of hydrochlorothiazide and timolol reduced the mean (formula: see text) blood pressure by 23 mm Hg, compared with a fall of nine mm Hg with administration of hydrochlorothiazide and a placebo. Plasma potassium (K+) levels fell with the administration of hydrochlorothiazide alone, but rose back to control values when patients were given timolol. In the second study (patient blind), Moduretic (hydrochlorothiazide, 50 mg and amiloride, 5 mg) and timolol were given once daily. The mean blood pressure fell by 20 +/- 2 mm Hg allowing hypertension to be controlled by this once-daily regimen; the control persisted throughout the day. Plasma potassium (K+) levels fell slightly after treatment with Moduretic, but the fall was not as great as with hydrochlorothiazide. Of the 65 patients who entered these studies, 35 had not been previously treated and had diastolic blood pressure between 105 mm Hg and 130 mm Hg. In 18 patients the diastolic blood pressure was reduced below 95 mm Hg after treatment with a diuretic alone, in 15 patients treatment with a diuretic and timolol (5 mg to 20 mg) reduced the diastolic blood pressure below 95 mm Hg. In two patients, the diastolic blood pressure was between 95 mm Hg and 100 mm Hg. The response achieved with a relatively simple therapeutic regimen that can be administered once daily suggests that the therapy of most hypertensive patients could be supervised by paramedical personnel.


The importance of nutrition in wound healing.
Nursing Standards recent Focus on Nutrition campaign raised some uncomfortable issues about nurses' knowledge of wound healing. We continue the theme here, with a review of the importance of good nutrition for effective wound healing.


Evaluation of posttransfusion recovery and survival of transfused red cells.
Increasing diversity of red cell preservation solutions has required more attention to the techniques of documenting the in vivo efficacy of stored red cell transfusion products. Use of double labels and survival studies will not only improve the precision of the measurement but, hopefully, will offer insight into some of the effects of the newer preservation systems. Further development of the low chloride hypotonic red cell storage solutions pioneered by Meryman may well result in red cell transfusion products that can be stored liquid in vitro for more than twice the normal in vivo lifespan. Verifying that such cells not only are recovered in the circulation but survive for the normal in vivo lifespan and function correctly will demand increasingly accurate techniques. The combination of assay precision and external imagability render radionuclide techniques the standard for verifying red cell efficacy despite the small disadvantage of the radiation absorbed dose.


Peripheral median nerve damage secondary to brachial arterial blood gas sampling.
Examination at 18 months post-term of 139 infants of birth weight less than or equal to 1,500 gm revealed 18 instances (13%) of persistent median nerve damage. All affected infants had received frequent percutaneous brachial artery punctures as neonates. Block sections of the cubital fossa done at autopsy on 12 randomly selected very low-birth-weight infants showed perineural hemorrhage, and Wallerian degeneration or traumatic neuroma of the median nerve in eight patients. It is recommended that brachial artery punctures be avoided whenever possible in the neonatal period.


Can the normobaric oxygen paradox (NOP) increase reticulocyte count after traumatic hip surgery?
To determine if the normobaric oxygen paradox (NOP) was effective in increasing reticulocyte count and reducing postoperative requirements for allogeneic red blood cell transfusion after traumatic hip surgery. Prospective, randomized, double blinded, multi-center study. Surgical wards of two academic hospitals. 85 ASA physical status 1 and 2 patients undergoing surgery for traumatic hip fracture. Patients were randomly assigned to receive 30 minutes of air [air group (control); n = 40] or 30 minutes of 100% oxygen (O2 group; n = 14) at 15 L/min every day from the first postoperative day (POD 1) until discharge. Venous blood samples were taken at admission and after surgery on POD 1, POD 3, and POD 7. Hemoglobin (Hb), hematocrit (Hct), reticulocytes, hemodynamic variables, and transfusion requirements were recorded, as were hospital length of stay (LOS) and mortality. Full analysis was obtained for 80 patients. On hospital discharge, the mean increase in reticulocyte count was significantly higher in the O2 group than the air group. Percent variation also increased: 184.9% ± 41.4% vs 104.7% ± 32.6%, respectively; P < 0.001. No difference in Hb or Hct levels was noted at discharge. Allogeneic red blood cell transfusion was 7.5% in the O2 group versus 35% in the air group (P = 0.0052). Hospital LOS was significantly shorter in the O2 group than the air group (7.2 ± 0.7 days vs 7.8 ± 1.6 days, respectively; P < 0.05). Transient O2 administration increases reticulocyte count after traumatic hip surgery. Hospital LOS also was shorter in the O2 group than the control group. Allogeneic red blood cell transfusion was reduced in the O2 group but it was not due to the NOP mechanism.


Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.
Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia. In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks. Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects. Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.


[Thinking and Methods for Demonstrating the Effectiveness of Chinese Herbal Compounds from the Perspective of Pharmacokinetics].
To exert pharmacological effects, no matter therapeutic effect or toxic/side effect, it's necessary to achieve enough plasma concentration. Chinese medical compounds, which contain various ingredients, influence the metabolism of some active ingredients through the interaction of ingredients to improve curative effects or reduce toxic/side effects. Pharmacokinetics can be used to explore how Chinese medical compounds influence the in vivo metabolism of some active ingredients to achieve better curative effects.


Assignment to chromosome 12 of the gene coding for the human cell surface antigen CD9(p24) using the monoclonal antibody ALB6.
An analysis of 20 independent man-mouse and man-hamster hybrids has shown that the gene coding for the cell-surface protein CD9(p24), a differentiation antigen recognized by the monoclonal antibody ALB6, is located on chromosome 12. A positive correlation was shown between CD9(p24) and chromosome 12 and all other chromosomes were excluded. In addition a synteny was observed between CD9(p24) and LDH-B, a well known marker of chromosome 12 (out of 27 hybrids, 15 were LDH-B+ ALB6+ and 12 were LDH-B-ALB6-). Expression of the antigen in hybrid CH-35K issued from parental fibroblasts possessing a balanced reciprocal translocation 46,X,Y,t(X,12)(q23,q12) indicated that the gene for CD9(p24) is probably localized on 12q12----pter. Monoclonal antibodies ALB6, Ba2 and 602/29 recognize the same protein of molecular weight 21 to 24 KD controlled by a gene located on chromosome 12. It is known that Ba2 and 602/29 recognize two different epitopes but the existence of a third epitope recognized by ALB6 remains to be shown.


Intrapulmonary gas mixing and pulmonary gas exchange in artificially ventilated dogs.
To investigate the effect of incomplete gas mixing between tidal air and residual gas on pulmonary gas exchange, anaesthetized dogs were ventilated artificially with breathing patterns with different durations of the post-inspiratory apnoea (ta = 0, 0.5, 1.0 and 2.0 s), where tidal volume, breathing frequency, inspiratory and expiratory flow patterns were kept constant. We determined the alveolar ventilations (VA) of He and SF6 from the product of end-expiratory lung volume (VL,E') and specific ventilation (VA/VL,E'). VL,E' was determined by the dilution technique and the specific ventilations of the two gases were obtained from their multiple-breath washout. Further, tracer amounts of acetone, ether and enflurane were infused continuously into a peripheral vein and a bolus of a gas mixture of krypton, Freon12 and SF6 was introduced into the peritoneal cavity. We determined the Excretion (E) and Retention (R) of these six gases according to the multiple-inert-gas-elimination technique (MIGET). VA increased with increasing ta, where VA,He was about 14% larger than VA,SF6. For both gases, however, the increase in VA relative to control (VA for ta = 0) was virtually the same: 9, 11 and 19% (mean values) for ta = 0.5, 1.0 and 2.0 s respectively. For all dogs the E/R curve shifted to larger E values with increasing ta. E for the most soluble tracer gas (acetone) increased by 11, 21 and 25% for ta = 0.5, 1.0 and 2.0 s respectively. VA, determined with MIGET from the ventilation/perfusion distribution, increased by almost the same percentages.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-Term Evaluation of the Spatial Distribution of Trophic Groups of Amoebae in the Rhizosphere of Zea mays Inoculated with Rhizophagus intraradices.
Primary production in terrestrial ecosystems is sustained by plants, microbiota, and fungi, which are the major organic matter providers in the root zone, setting in motion the soil food webs. Predators like soil amoebae voraciously feed on bacteria, fungi, and microbial eukaryotes releasing the nutrients sequestered in their biomass. Early food web setting up is crucial for seedling nutrition and its further development after establishment. Mycorrhizal fungi are more than phosphorus providers, and we wonder what their role is in structuring the predators' trophic groups in the root zone. We evaluated the effect of Rhizophagus intraradices inoculated in Zea mays (mycorrhizosphere), on the structuration of amoebae trophic groups along vertical and horizontal (3, 6, and 9 cm) soil distribution when compared to un-inoculated plants, after 20 days in microcosms. Amoebae species richness was highest in non-mycorrhizal seedlings in the root zone at 6- to 9-cm depth, and 3 cm away from plants. More bacterial species are needed when plants are devoid of mycorrhiza, and their influence is constrained 3 cm away from roots. Higher diversity of trophic groups was recorded at mycorrhizal seedlings and at the compartment influenced by the mycelium at 6- to 9-cm depth. The highest bacterivorous diversity, higher number of rare species and protozoa-eating amoebae, and the absence of fungivorous group recorded at the mycorrhizosphere of Z. mays, indicate that the community was very different from the non-mycorrhizal plants. We conclude that the arbuscular mycorrhizal fungus exerts significant changes on the community of trophic groups of amoebae.


Berry curvature dipole generation and helicity-to-spin conversion at symmetry-mismatched heterointerfaces.
The Berry curvature dipole (BCD) is a key parameter that describes the geometric nature of energy bands in solids. It defines the dipole-like distribution of Berry curvature in the band structure and plays a key role in emergent nonlinear phenomena. The theoretical rationale is that the BCD can be generated at certain symmetry-mismatched van der Waals heterointerfaces even though each material has no BCD in its band structure. However, experimental confirmation of such a BCD induced via breaking of the interfacial symmetry remains elusive. Here we demonstrate a universal strategy for BCD generation and observe BCD-induced gate-tunable spin-polarized photocurrent at WSe2/SiP interfaces. Although the rotational symmetry of each material prohibits the generation of spin photocurrent under normal incidence of light, we surprisingly observe a direction-selective spin photocurrent at the WSe2/SiP heterointerface with a twist angle of 0°, whose amplitude is electrically tunable with the BCD magnitude. Our results highlight a BCD-spin-valley correlation and provide a universal approach for engineering the geometric features of twisted heterointerfaces.


Visual evoked potential in the management of pituitary tumor during pregnancy.
We examined a pregnant woman with chiasmal syndrome in the late stage of pregnancy. Her vision was determined to be seriously threatened after 31 weeks' gestation. Study of the latency of preoperative visual evoked potentials (VEPs) in other patients with pituitary tumor showed that insofar as latency is not delayed, surgical decompression is expected to be followed by functional improvement of the optic pathway. We monitored optic nerve function by serially recorded VEPs, and labor was induced at 38 weeks because there had been no delayed response up to that time. After a decompressive operation, visual field and visual acuity recovered normally. Serially recorded VEPs can provide a useful monitor along with visual field and acuity tests in guiding therapy for a patient with threatened vision in late pregnancy and in determining whether or when to induce labor.


Diagnosis of Respiratory Syncytial Virus in Adults Substantially Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT-PCR.
Nearly all existing respiratory syncytial virus (RSV) incidence estimates are based on real-time polymerase chain reaction (RT-PCR) testing of nasal or nasopharyngeal (NP) swabs. Adding testing of additional specimen types to NP swab RT-PCR increases RSV detection. However, prior studies only made pairwise comparisons and the synergistic effect of adding multiple specimen types has not been quantified. We compared RSV diagnosis by NP swab RT-PCR alone versus NP swab plus saliva, sputum, and serology. This was a prospective cohort study over two study periods (27 December 2021 to 1 April 2022 and 22 August 2022 to 11 November 2022) of patients aged ≥ 40 years hospitalized for acute respiratory illness (ARI) in Louisville, KY. NP swab, saliva, and sputum specimens were collected at enrollment and PCR tested (Luminex ARIES platform). Serology specimens were obtained at acute and convalescent timepoints (enrollment and 30-60-day visit). RSV detection rate was calculated for NP swab alone and for NP swab plus all other specimen type/test. Among 1766 patients enrolled, 100% had NP swab, 99% saliva, 34% sputum, and 21% paired serology specimens. RSV was diagnosed in 56 (3.2%) patients by NP swab alone, and in 109 (6.2%) patients by NP swab plus additional specimens, corresponding to a 1.95 times higher rate [95% confidence interval (CI) 1.62, 2.34]. Limiting the comparison to the 150 subjects with all four specimen types available (i.e., NP swab, saliva, sputum, and serology), there was a 2.60-fold increase (95% CI 1.31, 5.17) compared to NP swab alone (3.3% versus 8.7%). Sensitivities by specimen type were: NP swab 51%, saliva 70%, sputum 72%, and serology 79%. Diagnosis of RSV in adults was several-fold greater when additional specimen types were added to NP swab, even with a relatively low percentage of subjects with sputum and serology results available. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT-PCR should be adjusted for underestimation.


A method to visually observe the degradation-diffusion-reconstruction behavior of hydroxyapatite in the bone repair process.
Nanostructured hydroxyapatite (HAp) has been applied widely as a scaffold material for bone tissue engineering for its good osteoinduction and biodegradability. However, the degradation process and the distribution of degraded HAp within the bone-defect cavity is still not clear. To visually study the behavior of HAp in bone repair process, a membrane of HAp/terbium (Tb)-HAp nanowires (NWs) was prepared with a concentric circle structure (CCS), of which the inner circle and the outer ring were constructed with Tb-HAp and HAp NWs, respectively. HAp/Tb-HAp CCS membrane possessed good osteogenic capacity and efficient fluorescence in the center for visualization. The in vitro experimental results proved that the Tb-HAp and HAp NWs membranes both presented high cytocompatibility and adequate efficiency to induce osteogenic differentiation of bone marrow stem cells (BMSCs). HAp/Tb-HAp CCS membranes were then implanted into a rat calvarial bone-defect model to study the behavior of HAp in bone repair process in vivo by tracking the fluorescence distribution. The results showed that the fluorescence of Tb-HAp diffused gradually from the inner circle to the outer ring, which suggested that the HAp was first degraded, and then the degraded product was diffused and finally reconstructed. Further, the histological results proved that the doping of Tb did not impair the promotive effect of HAp on bone repair process. Therefore, this study provided a visual method to observe the degradation-diffusion-reconstruction behavior of HAp nanomaterials in bone repair process. STATEMENT OF SIGNIFICANCE: The study of dynamic degradation process of implanted hydroxyapatite (HAp) materials in bone-defect cavity is of great significance to bone tissue engineering applications. Here, we designed a HAp/Tb-HAp nanowires (NWs) membrane with concentric circle structure (CCS) to visibly observe the behavior of HAp during bone repair process. HAp/Tb-HAp CCS membrane possessed both osteoinduction ability and fluorescence property. Calvarial bone-defect repair experiments in vivo showed that the fluorescence of Tb-HAp diffused gradually from inner circle to outer ring, which suggested that HAp was first degraded, then diffused and finally reconstructed. Therefore, this invention provides not only a visible method to observe the degradation-diffusion-reconstruction behavior of HAp-based biomaterials, but also a basic understanding of the dynamic change of HAp-based biomaterials.


Investigating the effect of red beetroot powder concentration and processing time on the bioactive compounds composition and antioxidant capacity of beetroot dark chocolate.
The development of functional foods is receiving increased recognition as a result of the general interest in healthy diets as part of a healthier lifestyle. This project sought to incorporate red beetroot in dark chocolate and investigate the effect of beetroot powder concentration and processing time on the chocolates' bioactive compound composition, antioxidant capacity, and sugar content. The results showed the presence of bioactive compounds such as betalains and vitamin C in the red beetroot with relatively high antioxidant capacity. The addition of beetroot powder to dark chocolate increased the majority of the bioactive compounds (e.g. catechin, epicatechin, betalains, vitamin C) while at the same time increasing the antioxidant capacity. It also resulted in a decrease in sugar content. Except for vitamin C, processing for more than 12 h had an increasing effect on the majority of the bioactive compounds. Beetroot powder incorporation at a maximum of 30% and processing for 24 h was regarded as optimal. Overall, the present study suggests that red beetroot powder could be added to dark chocolates and processed for more than 12 h to increase the bioactive compounds and overall antioxidant capacity. This research would help to diversify beetroot utilization, reduce post-harvest losses, and improve the overall health-promoting properties of dark chocolate for improved consumer well-being. © 2023 Society of Chemical Industry.


The cost of mutualism: interactions between Trollius europaeus and its pollinating parasites.
Pollination by seed parasites is unusual, and previously studied case involve plant species (figs, yuccas) that are pollinated mostly by one host-specific pollinator. Trollius europaeus (Ranunculaceae), however, is pollinated by four Chiastocheta species (Diptera: Anthomyiidae) that mate in the flowers, eat pollen and nectar, and complete larval development in the seeds. Strict resource partitioning is present between the fly species, in that different parts of the infructescence are used by larvae of each species, and fly species oviposit at different times in the life of a flower. The flies were shown to be the exclusive pollinators. Because the numbers of ovules fertilized per visit was a fixed proportion of remaining non-fertilized ovules, fly species differed in mean pollinator efficacy, with the last species contributing the fewest pollinations. Therefore, with larval consumption of seeds being fixed and seed initiation decreasing per visit, larvae from later ovipositions consumed more seeds than their mothers pollinated. The point at which costs and benefits were equal was found to be around 4-5 eggs; observed population means of eggs per flower varied between 2.3-7.25 during three years of study. The system is rather insensitive to variation in pollinator density, remaining mutualistic over a wide range. Small changes in pollinator efficacy, however, can tilt the equilibrium to a negative net effect for the plant. These data on Trollius/ Chiastocheta interactions provide the first extensive cost/ benefit analyses for mutualism based on seed parasites as pollinators.


Cystic fibrosis bone disease: Pathophysiology, assessment and prognostic implications.
Cystic fibrosis bone disease (CFBD) is a common long-term complication of cystic fibrosis (CF) that can lead to increased fractures and significant morbidity and mortality in this patient population. CFBD pathophysiology remains poorly understood and is likely to be multifactorial. There are limited studies evaluating diagnostic tools and tests to guide therapeutic decisions and monitoring of CFBD. This review will present and discuss the current evidence.


Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects.
Gilbert's syndrome is a chronic or recurrent mild unconjugated hyperbilirubinemia caused by decreased activity of UDP glucuronosyltranferase (UGT1A1). The most common cause of Gilbert's syndrome in Caucasians is homozygous variant of the A(TA)7TAA promoter polymorphism. Alleles with five or eight TA repeats have also been described, but they are very rare in Caucasian populations. Over a 6-year period (2001-2006), 1109 subjects with suspected Gilbert's syndrome were included in this study. Genotyping of (TA)6 and (TA)7 alleles was performed using high-resolution electrophoretic separation of amplified PCR products on Spreadex EL300 gels. In seven subjects, aberrant electrophoretic patterns were observed and additionally sequenced on an ABI Prism 310 Genetic Analyzer. Genotype distributions for 1102 subjects with (TA)6 or (TA)7 alleles were as follows: 54.10%, 26.33% and 18.94% for the (TA)7/(TA)7, (TA)6/(TA)7 and (TA)6/(TA)6, respectively. Sequencing of seven samples that could not be identified as one of these alleles identified four subjects with the (TA)5/(TA)7, two with the (TA)7/(TA)8 and one with the (TA)6/(TA)8 genotype. Genotyping of TA repeats in the promoter region of the UGT1A1 gene revealed the presence of rare alleles with five or eight TA repeats, with a very high frequency of the (TA)7 allele in subjects suspected of having Gilbert's syndrome.


Dimethylarginines as risk markers of atherosclerosis and chronic kidney disease in children with nephrotic syndrome.
Nephrotic syndrome in children is commonly associated with dyslipidemia, which is considered a risk factor for endothelial dysfunction and atherosclerosis. Recently new markers of endothelial dysfunction, such as asymmetric dimethylarginine (ADMA), have gained importance. Another L-arginine derivative--symmetric dimethylarginine (SDMA)--may reflect the glomerular filtration rate (GFR). The main aim of this study was to assess ADMA as a marker of atherosclerosis. Secondly, SDMA was examined for GFR assessment. The study involved 32 children with nephrotic syndrome. Several parameters were examined in the remission and relapse phases of nephrotic syndrome, including ADMA, SDMA, cholesterol, triglycerides and GFR. In the relapse phase there was a negative correlation between ADMA and lipids (cholesterol and triglycerides). In both phases SDMA was negatively correlated with GFR. The role of ADMA as a marker for endothelial dysfunction is not significant. SDMA may be utilized to monitor GFR in children with nephrotic syndrome.


Reviewing the role of positive classroom climate in improving English as a foreign language students' social interactions in the online classroom.
The teacher and learners are cooperatively involved in the creation of a positive climate in an L2 class. In the online language learning environment today, teachers can make the best use of technology, multimedia learning, and accessibility of learners to create a supportive and effective climate. In this productive climate, the teacher and learners can have multiple forms of social interaction which can improve language learners' communicative skills. Not only can the teacher expect better learning outcomes, but s/he can also ensure students' wholehearted attendance in, attention to, and participation in class activities. A positive class climate and the consequent better social interactions can also enhance learners' affective well-being. For example, higher self-esteem leads to lower levels of anxiety and better emotional health. This study aims to review the contribution of a positive classroom climate to the improvement of students' social interaction in the online L2 classroom. To do this, the findings of the relevant studies have been presented and their implications for the construction of a positive online L2 classroom climate have been provided. Suggestions are made on how to help teachers create a positive climate in online L2 classes and how to pave the way for more effective social interactions between teachers and students and among students. Also, implications are provided for L2 teachers, researchers, and trainers, especially in the post-pandemic era.


Silica-rubber microstructure visualised in three dimensions by focused ion beam-scanning electron microscopy.
A focused ion beam-scanning electron microscope (FIB-SEM) technique for three-dimensional reconstruction and representation of material microstructures was applied to a silica-filled synthetic rubber for the first time. Backscattered electron imaging allowed differentiation between rubber matrix, silica filler and zinc oxide (used as an activator for the sulphur vulcanisation reaction). Subsequent image processing allowed three-dimensional isosurface model generation of the particulate structure within the rubber composite and separation of zinc oxide from the silica filler. The potential for development and application of this technique using finite element analysis modelling is also highlighted.


Effect of magnesium and calcium on myocardial protection by cardioplegic solutions.
The cardioprotective effect of the magnesium and calcium content of hyperkalemic cardioplegic solutions was investigated using isolated rat hearts subjected to hypothermic ischemic arrest. Hearts were arrested for 180 minutes at 20 degrees C by administering a 3-minute infusion of cardioplegic solution containing various concentrations of magnesium and calcium. Treatment groups received solution with either 0, 8, or 16 mmol/L magnesium. For each of these magnesium concentrations, 0.1, 0.6, or 1.2 mmol/L calcium was also present in the solution. At each concentration of magnesium, the percentage recovery of aortic flow was dependent on the calcium concentration. The maximum percentage recovery of aortic flow was 67.9% +/- 2.3% (mean +/- standard error of the mean) in the Mg-free, 0.1 mmol/L Ca group, whereas it was 65.1% +/- 2.7% in the 8 mmol/L Mg, 0.1 mmol/L Ca group and 70.0% +/- 3.5% in the 16 mmol/L Mg, 0.6 mmol/L Ca group. No significant differences in the recovery of cardiac function and creatine kinase leakage were observed between the three groups. The findings suggested that the cardioprotective effect was dependent on the relative concentration of both magnesium and calcium, and that it is important to maintain an appropriate ionic balance in cardioplegic solutions.


Cholecystectomy and a simple technique of operative cholangiography.
A simple, easily reproducible technique of operative cholangiography is described. The technique has three advantages: (a) there is no need to divide or ligate the cystic duct; (b) it demonstrates the cystic duct anatomy clearly and is particularly useful in demonstrating stones in that duct thus eliminating the hazard of the retained stone in the cystic duct stump; (c) it is possible to eliminate the problem of false positives due to air bubbles. A consecutive series of 442 cholecystectomy patients is reviewed. The overall operative mortality was 1.6 per cent; no death could be attributed to operative cholangiography. Thirty-five of 324 patients (10.8 per cent) with gallstones and no history of jaundice were shown to have unexpected abnormalities in the common bile duct.


Cytomegalovirus antibody detection in blood donors and mothers of very low birth weight neonates by using three serologic methods.
We compared three serologic methods for cytomegalovirus (CMV) antibody detection and determined the CMV antibody seroprevalence of blood donors and mothers of very low birth weight (less than 1250 g) neonates in the Greater Hartford region. CMV serology was determined for 577 healthy blood donors as well as for 147 mothers of premature infants. Plasma from blood donors and sera from mothers were tested by either latex agglutination (LA) or by an immunofluorescent antibody assay (IFA), and results were compared with those from an enzyme-linked immunosorbent assay (ELISA). Sensitivity and specificity for LA to ELISA were significantly better than for IFA to ELISA [sensitivity 79/81 (97%) vs 171/202 (85%), and specificity 90/94 (96%) vs 257/347 (74%), p less than 0.01]. These differences remained whether plasma or sera were tested. Borderline values explained only two (33%) of six LA-ELISA as well as only 70 (58%) of 121 IFA-ELISA discordance. CMV seroprevalence rate for the donor blood population was 38%, and for the mothers was 53%. The LA assay is superior to the IFA assay for CMV screening of blood donors and maternal populations.


High Quality Independent From a Donor: Human Amniotic Fluid Derived Stem Cells-A Practical Analysis Based on 165 Clinical Cases.
The aim of the study was to extend the potential use of human stem cells isolated from amniotic fluid in medical applications by confirming their high homogeneity and quality. Amniotic fluid samples were collected during amniocentesis from 165 women during pregnancy. The proliferation rate, clonogenicity, karyotype, aging process, pluripotent cell markers, expression of surface markers, and the potential to differentiate into adipose, bone and cartilage cells of hAFSCs were analyzed. Obtained results revealed that mesenchymal stem cells could be derived successfully from amniotic fluid, which exhibit properties comparable with MSCs of other origins. It is the first study, in which such a large group of patients was involved. Comprehensive statistical and biological analysis were conducted some of which clearly being innovative in relation to human amniotic fluid-derived stem cells. J. Cell. Biochem. 118: 116-126, 2017. © 2016 Wiley Periodicals, Inc.


Bullous pemphigoid and malignancy: relationship to indirect immunofluorescent findings.
In a group of 93 patients with generalized bullous pemphigoid seen at the Mayo Clinic from 1970 to 1980, the frequency of concomitant malignancies did not appear to be higher than in the general population or in previously reported series from the Mayo Clinic. However, the subgroup with negative indirect immunofluorescent tests had an unexplained higher frequency of malignancy (4/28) than the subgroup with positive immunofluorescent tests (5/65).


Somatosensory evoked potentials via lumbosacral pathways: a comment on naturalistic stimulation.
Somatosensory evoked potentials (SEPs) were averaged from several scalp derivations in 3 subjects (1 M, 2 F) for transcutaneous electrical stimulation of toes and perineum. These lumbosacral SEPs were amplitude-focal at vertex for 40-300 msec components. Peak latencies in the 40-120 msec time segment were significantly later for perineal stimulation of equivalent subjective magnitude, contrary to expectation from relative afferent pathway lengths. One subject (M) showed a monotonic latency retardation of an intermediate component (SP50-SN75) for equivalent stimuli at lips, fingers, toes, genitalia, and perianum. Vertex potentials (SN140-SP200) did not show this temporal sequence. Though interpretation of such data is currently ambiguous, systematic application of comparative evoked potential/magnetic field techniques could yield data useful to clinical neurologists.


Induction of severe tumor hypoxia by modifiers of the oxygen affinity of hemoglobin.
Methods have been compared for inducing severe hypoxia in experimental tumors. Hypoxic fractions in the tumors were obtained from measurements of the displacement of cellular survival plots in vitro following tumor irradiation in vivo. Two compounds that displace to the left, oxygen-hemoglobin association curves greatly increase the hypoxic fractions in the tumors. The compound BW12C increases the hypoxic fractions in the KHT and Lewis-Lung tumors from about 10% to between 50-100%. The longer acting analogue BW589C increases hypoxic fraction in the KHT tumor to the same level achievable by treatment with the vaso-active drug hydralazine. The effect is also observed in the RIF-1 tumor even though the hypoxic fraction in this tumor is normally only about 1-3%. The kinetics for hypoxia induction by BW589C and its subsequent return to normal levels are comparable to those for the left-shifting of the oxy-hemoglobin association curve observable up to about 2 days post treatment.


Primary glomerular diseases in Brazil (1979-1999): is the frequency of focal and segmental glomerulosclerosis increasing?
Different patterns of glomerulonephritis (GN) are reported from all over the world and the occurrence of primary GN is changing in the course of time. We report the frequencies of primary GN in a major teaching hospital in Brazil, from 1979-1999. The case files of renal biopsies of primary GN were reviewed. The included patients were > 14 years of age, with native kidneys, and the specimens were examined with at least light and immunofluorescence microscopy. We excluded biopsy results of patients with any kind of known secondary glomerular involvement. Differences in proportions of diagnoses between the periods over time were evaluated using Chi-square test for trend. We considered 943 patients for the analysis. Focal and segmental glomerulosclerosis (FSGS) was the most common lesion (n = 279), followed by membranous GN (n = 140), membranoproliferative type I GN (n = 109) and IgA nephropathy (n = 109). FSGS (32.1%) was the most frequent diagnosis among nephrotic patients whereas IgAN (29.4%) predominated in non-nephrotic ones. The occurrence of FSGS increased from the earlier to the later periods: 22.3% (1979-1983), 23.7% (1984-1988), 35.7% (1989-1993), 33.9% (1994-1999), p < 0.05. The increase in frequency of FSGS was proportionally higher in non-nephrotic patients and FSGS became as common as IgA nephropathy in this group (31.6% and 28.0%, respectively) from 1994-1999. FSGS was the most common pattern of primary glomerulonephritis and its relative frequency seems to be increasing in biopsied patients over time. The reasons for this behavior are unclear and warrant further investigations.


Upper ureteric obstruction secondary to entrapment between twin segments of inferior vena cava--an unusual occurrence.
A retrocaval ureter is a rare congenital cause of upper ureteric obstruction that results from entrapment of the upper ureter by the inferior vena cava (IVC) as it courses posterior to the cava. We report an interesting scenario of upper ureteric obstruction secondary to entrapment between twin segments of IVC.


Contemporary National Outcomes of Acute Myocardial Infarction-Cardiogenic Shock in Patients with Prior Chronic Kidney Disease and End-Stage Renal Disease.
There are limited data on acute myocardial infarction with cardiogenic shock (AMI-CS) stratified by chronic kidney disease (CKD) stages. To assess clinical outcomes in AMI-CS stratified by CKD stages. A retrospective cohort of AMI-CS during 2005-2016 from the National Inpatient Sample was categorized as no CKD, CKD stage-III (CKD-III), CKD stage-IV (CKD-IV) and end-stage renal disease (ESRD). CKD-I/II were excluded. Outcomes included in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS). We also evaluated acute kidney injury (AKI) and acute hemodialysis in non-ESRD admissions. Of 372,412 AMI-CS admissions, CKD-III, CKD-IV and ESRD comprised 20,380 (5.5%), 7367 (2.0%) and 18,109 (4.9%), respectively. Admissions with CKD were, on average, older, of the White race, bearing Medicare insurance, of a lower socioeconomic stratum, with higher comorbidities, and higher rates of acute organ failure. Compared to the cohort without CKD, CKD-III, CKD-IV and ESRD had lower use of coronary angiography (72.7%, 67.1%, 56.9%, 61.1%), PCI (53.7%, 43.8%, 38.4%, 37.6%) and MCS (47.9%, 38.3%, 33.3%, 34.2%), respectively (all p < 0.001). AKI and acute hemodialysis use increased with increase in CKD stage (no CKD-38.5%, 2.6%; CKD-III-79.1%, 6.5%; CKD-IV-84.3%, 12.3%; p < 0.001). ESRD (adjusted odds ratio [OR] 1.25 [95% confidence interval {CI} 1.21-1.31]; p < 0.001), but not CKD-III (OR 0.72 [95% CI 0.69-0.75); p < 0.001) or CKD-IV (OR 0.82 [95 CI 0.77-0.87] was predictive of in-hospital mortality. CKD/ESRD is associated with lower use of evidence-based therapies. ESRD was an independent predictor of higher in-hospital mortality in AMI-CS.


Ionizing radiation suppresses FAP-1 mRNA level in A549 cells via p53 activation.
Ionizing radiation (IR) is known to upregulate cell surface Fas through p53 activation in various cells. However, the signaling pathway intermediating between p53 activation and cell surface Fas upregulation remains to be elucidated. Recently, Fas-associated phosphatase-1 (FAP-1) has been reported to associate with Fas and inhibit cell surface Fas expression. We evaluated the expression of FAP-1 mRNA following IR in A549 cells. Ionizing radiation inhibited the expression of FAP-1 mRNA. Pretreatment with p53 inhibitor pifithrin alpha cancelled the IR-induced downregulation of FAP-1 mRNA. These results suggest that IR-induced p53 activation may upregulate cell surface Fas via the down-modulation of FAP-1.


Surface carbohydrate analysis and bioethanol production of sugarcane bagasse pretreated with the white rot fungus, Ceriporiopsis subvermispora and microwave hydrothermolysis.
Effects of pretreatments with a white rot fungus, Ceriporiopsis subvermispora, and microwave hydrothermolysis of bagasse on enzymatic saccharification and fermentation were evaluated. The best sugar yield, 44.9 g per 100g of bagasse was obtained by fungal treatments followed by microwave hydrothermolysis at 180°C for 20 min. Fluorescent-labeled carbohydrate-binding modules which recognize crystalline cellulose (CjCBM3-GFP), non-crystalline cellulose (CjCBM28-GFP) and xylan (CtCBM22-GFP) were applied to characterize the exposed polysaccharides. The microwave pretreatments with and without the fungal cultivation resulted in similar levels of cellulose exposure, but the combined treatment caused more defibration and thinning of the plant tissues. Simultaneous saccharification and fermentation of the pulp fractions obtained by microwave hydrothermolysis with and without fungal treatment, gave ethanol yields of 35.8% and 27.0%, respectively, based on the holocellulose content in the pulp. These results suggest that C. subvermispora pretreatment could be beneficial part of the process to produce ethanol from bagasse.


Identification and characterization of the AgmR regulator of Pseudomonas putida: role in alcohol utilization.
Two-phase partitioning bioreactors (TPPBs) comprise an aqueous phase containing all non-carbon nutrients necessary for microbial growth and a solvent phase containing high concentrations of inhibitory or toxic substrates that partition at sub-inhibitory levels to the aqueous phase in response to cellular demand. This work aimed at eliminating the growth of Pseudomonas putida ATCC 11172 on medium-chain-length (C8-C12) aliphatic alcohols, hence enabling their use as xenobiotic delivery solvents within two-phase partitioning bioreactors. Experiments resulted in the isolation of a mini-Tn5 mutant unable to utilize these alcohols. The mutation, which also eliminated growth on glycerol and ethanol, was identified to be within a homologue of the P aeruginosa agmR gene, which encodes a response regulator. Enzyme analysis of the agmR::Tn5Km mutant cell extracts revealed a 10-fold decrease in pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenase activity. A knockout in a gene (exaA) encoding a PQQ-linked alcohol dehydrogenase slowed but did not eliminate growth on medium-chain-length alcohols or ethanol, suggesting metabolic redundancy within P. putida ATCC 11172. Analysis of P. putida KT2440 genome sequence data indicated the presence of two PQQ-linked alcohol dehydrogenase-encoding genes. The successful elimination of alcohol utilization in the agmR mutant indicates control by AgmR on multiple pathways and presents a useful strain for biotechnological applications requiring alcohol non-utilizing microbial catalysts.


Therapy with anti-flagellin A monoclonal antibody limits Pseudomonas aeruginosa invasiveness in a mouse burn wound sepsis model.
The aim of this study was to evaluate the effect of an anti-flagellin sub-type monoclonal antibody (anti-fla-a) on Pseudomonas aeruginosa infection in a mouse burn model and to assay bacterial dissemination and invasiveness. After immediate post-burn infection with P. aeruginosa, mortality and morbidity (daily weight changes) were monitored in mice treated with anti-fla-a as compared to untreated mice. Bacterial dissemination and invasiveness were monitored by bacterial counts at the burn site and spleen. Three different timing regimens for anti-fla-a treatment were studied: (a) prophylaxis (pre-infection), (b) therapeutic (post-infection), and (c) combined mode. Combined regimen of anti-fla-a markedly improved survival of mice infected with P. aeruginosa from 6% to 96% (p<0.0001), similar to treatment with Imipenem. Furthermore, a significant improvement in survival was obtained when anti-fla-a was given prior to (75% survival) or post-infection (50% survival). It reduced bacterial load in the spleen (p=0.01), preventing bacterial sepsis. Anti-fla-a is effective in reducing mortality and morbidity in murine P. aeruginosa-infected burn model.


SIRT6 Negatively Regulates Schwann Cells Dedifferentiation via Targeting c-Jun During Wallerian Degeneration After Peripheral Nerve Injury.
Silent information regulator 6 (SIRT6) is a mammalian homolog of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin family. Previous studies have been reported a pro-regenerative role of SIRT6 in central nervous system injury. However, the role of SIRT6 in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of SIRT6 steering Schwann cell dedifferentiation during Wallerian degeneration in injured peripheral nerve. Herein, we first examined the expression pattern of SIRT6 after peripheral nerve injury. Using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that SIRT6 inhibitor accelerates Schwann cell dedifferentiation as well as axonal and myelin degeneration, while SIRT6 activator attenuates this process. Moreover, in an in vitro Schwann cell dedifferentiation model, we found SIRT6 inhibitor promotes Schwann cell dedifferentiation through upregulating the expression of c-Jun. In addition, downregulation of c-Jun reverse the effects of SIRT6 inhibition on the Schwann cells dedifferentiation and axonal and myelin degeneration. In summary, we first described SIRT6 acts as a negative regulator for Schwann cells dedifferentiation during Wallerian degeneration and c-Jun worked as a direct downstream partner of SIRT6 in injured peripheral nerve.


Surgical procedures for reconstruction of the lower jaw using the titanium-coated hollow-screw reconstruction plate system: bridging of defects.
The various advantages rendered by the system described enable primary as well as long-term functional stability even in cases in which conventional systems would be insufficient. The evaluation of 49 cases managed in Bern and Sweden confirm the efficiency of this reconstruction system.


Effects of cerulenin on the endogenous fatty acid synthetic activity in squamous cell carcinoma of the oral cavity.
Inhibition of cerulenin on the endogenous fatty acid synthetic activities of oral squamous cell carcinoma (OSCC) and normal oral mucosa was assayed. Squamous cell carcinoma and normal oral mucosa were collected fresh from surgical specimens. The collected tissues were minced in RPMI 1640 and divided into 3 groups: cerulenin treated, dimethylsulfoxide treated, and control. The tissues were incubated in [1(2)-(14)C]acetic acid, sodium salt for the last 2.5 hours of the treatment at 37 degrees C in 5% CO(2). After labeling, total lipids were extracted and counted for (14)C by scintillation counting. Endogenous fatty acid synthetic activities of oral squamous cell caranoma in the cerulenin-treated group decreased by 19% at 1 hour, 64% at 2 hours, and 87% at 4 hours; remained nearly unchanged in the dimethylsulfoxide-treated group; and increased slightly in the control group. The oral mucosa tissues were only mildly affected by cerulenin in fatty acid synthesis. Cerulenin significantly inhibits fatty acid synthetic activity in squamous cell carcinoma and only mildly affected the oral mucosa, indicating that the fatty acid synthetic pathway may be exploited as a target for developing anticancer drugs.


Selective vulnerability of the CA1 region of hippocampus to the indirect excitotoxic effects of malonic acid.
The CA1 region of hippocampus is selectively vulnerable to a variety of insults, including hypoxia-ischemia and Alzheimer's disease, but the basis of this regional susceptibility is poorly understood. We examined the regional hippocampal sensitivity to mitochondrial metabolic disruption induced by malonate, an inhibitor of succinate dehydrogenase. The CA1 region was exquisitely sensitive to malonate and the dentate gyrus was extremely resistant; the CA3 region had intermediate sensitivity. This pattern of vulnerability is reminiscent of hypoxic-ischemic damage. Malonate damage was blocked by the N-methyl-D-aspartic acid (NMDA) antagonist, MK-801, but regional susceptibility to malonate did not correlate with the density of NMDA receptors. Instead, malonate toxicity was inversely correlated with activity of succinate dehydrogenase. Our results suggest that regional metabolic capacity may help to determine sensitivity to metabolic/excitotoxic insults such as hypoxia-ischemia.


Complex migration of antibiotic resistance in natural aquatic environments.
Antibiotic resistance is a worsening global concern, and the environmental behaviors and migration patterns of antibiotic resistance genes (ARGs) have attracted considerable interest. Understanding the long-range transport of ARG pollution is crucial. In this study, we characterized the dynamics of ARG changes after their release into aquatic environments and demonstrated the importance of traditional chemical contaminants in the transmission mechanisms of ARGs. We hypothesized that the main route of ARG proliferation switches from active transmission to passive transmission. This antibiotic-dominated switch is motivated and affected by non-corresponding contaminants. The effect of anthropogenic activities gradually weakens from inland aquatic environments to ocean environments; however, the effect of changes in environmental conditions is enhanced along this gradient. The insights discussed in this study will help to improve the understanding of the distribution and migration of ARG pollution in various aquatic environments, and provide a modern perspective to reveal the effect of corresponding contaminants and non-corresponding contaminants in the process of antibiotic resistance proliferation.


Urinary tract diversion with gastric conduit after total pelvic exenteration for Crohn's disease-related anorectal cancer: a case report.
In Japan, Crohn's disease (CD)-related cancers occur most frequently in the anal canal. Many patients with advanced CD-related cancer require total pelvic exenteration (TPE) based on their medical history, and choosing the most effective method for urinary diversion is a major concern. We herein report the first case of CD-related cancer treatment with urinary diversion using a gastric conduit after TPE in Japan. A 51-year-old man with a 25 year history of CD was referred to our institution after having been diagnosed with fistulae between the rectum and urethra. Sigmoidoscopy revealed stenosis of the anal canal, and histological examination of this lesion led to a diagnosis of mucinous adenocarcinoma. Magnetic resonance imaging showed that the tumor had invaded the prostate and left internal obturator muscle, and TPE with left internal obturator muscle resection was planned. Urinary diversion was performed with a gastric conduit. The gastric conduit was created by trimming a gastric tube to a 1.5 cm width via stapled resection of the greater curvature, and the branches of the right gastroepiploic artery were preserved as feeding vessels. The ureters were raised from the mesentery on the right side of the ligament of Treitz. Ureterogastric anastomosis was performed using the Wallace technique, and the entire anastomosis was then retroperitonealized. The anastomotic site had a bleeding tendency, but hemostasis was obtained by proton pump inhibitor administration and discontinuation of enoxaparin, which had been administered to prevent venous thrombosis. No other major complications occurred, and the patient's quality of life was recovered 6 months after surgery. Urinary diversion using a gastric conduit is a feasible treatment option for patients with CD-related anorectal cancer requiring TPE.


Imaging-Based Screening of Deubiquitinating Proteases Identifies Otubain-1 as a Stabilizer of c-MYC.
The ubiquitin-proteasome pathway precisely controls the turnover of transcription factors in the nucleus, playing an important role in maintaining appropriate quantities of these regulatory proteins. The transcription factor c-MYC is essential for normal development and is a critical cancer driver. Despite being highly expressed in several tissues and malignancies, the c-MYC protein is also continuously targeted by the ubiquitin-proteasome pathway, which can either facilitate or inhibit c-MYC degradation. Deubiquitinating proteases can remove ubiquitin chains from target proteins and rescue them from proteasomal digestion. This study sought to determine novel elements of the ubiquitin-proteasome pathway that regulate c-MYC levels. We performed an overexpression screen with 41 human proteases to identify which deubiquitinases stabilize c-MYC. We discovered that the highly expressed Otubain-1 (OTUB1) protease increases c-MYC protein levels. Confirming its role in enhancing c-MYC activity, we found that elevated OTUB1 correlates with inferior clinical outcomes in the c-MYC-dependent cancer multiple myeloma, and overexpression of OTUB1 accelerates the growth of myeloma cells. In summary, our study identifies OTUB1 as a novel amplifier of the proto-oncogene c-MYC.


A molecular and ecological study of Macracanthorhynchus ingens (von Linstow, 1879) (Acanthocephala: Archiacanthocephala), in its paratenic and definitive hosts in southeastern Mexico and the Eastern USA.
The acanthocephalan Macracanthorhynchus ingens (von Linstow 1879) (Acanthocephala: Archiacanthocephala) is a parasite that infects the gut of carnivores (racoons, coyotes, wolves, foxes, badgers, skunks, opossum, mink and bears) as an adult and the body cavity of lizards, snakes, and frogs as a cystacanth in the Americas. In this study, adults and cystacanths of M. ingens from southeastern Mexico and southern Florida, USA, were identified morphologically by having a cylindrical proboscis armed with 6 rows of hooks each with 6 hooks. Hologenophores were used to sequence the small (SSU) and large (LSU) subunits of ribosomal DNA and cytochrome c oxidase subunit 1 (cox 1) from mitochondrial DNA. Phylogenetic analysis of the new SSU and LSU sequences of M. ingens placed them in a clade with other sequences available in GenBank identified as M. ingens. The cox 1 tree showed that the nine new sequences and six previously published sequences of M. ingens from the USA form a clade with other sequences previously identified as M. ingens from GenBank. The intraspecific genetic divergence among isolates from the Americas ranged from 0 to 2%, and in combination with the phylogenetic trees confirmed that the isolates belonged to the same species. The cox 1 haplotype network inferred with 15 sequences revealed 10 haplotypes separated from each other by a few substitutions. Rio Grande Leopard Frogs and Vaillant´s Frogs harbored cystacanths with low prevalence, 28% and 37% respectively, in Mexico. Brown Basilisks, an invasive lizard in Florida, USA, had high values of prevalence, 92% and 93% in males and females, respectively. Females harbored more cystacanths than males (0-39 vs 0-21) for unknown reasons that may, however, be related to ecological differences.


Association between bone turnover markers, BMD and height loss of cemented vertebrae after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures.
Percutaneous vertebroplasty (PVP) was recently performed for treating patients with osteoporotic vertebral compression fractures (OVCF). However, recompression of cemented vertebra with significant vertebral height loss occurred in the patients after PVP was observed during the follow-up period. The purpose is to explore the risk factors among several potential predictors for the height loss of treated vertebral bodies after PVP in patients with OVCF. A study of 93 patients who had undergone PVP between May 1, 2016, and March 1, 2019, at the Spine Center of Huadong Hospital Affiliated to Fudan University was conducted. The fractured vertebral height loss ratio ≥ 15% at final follow-up were defined as cemented vertebra recompression. The following variables were measured and collected: age, gender, body mass index (BMI), bone mineral density (BMD), volume of bone cement injected, bone cement leakage, fractured vertebra segment, contact between bone cement and endplates, serum of calcium and phosphorus, and six kinds of bone turnover markers. Mann-Whitney U test and Univariate Logistic regression analysis showed that the cemented vertebra recompression was correlated with BMD, contact between bone cement and endplates, parathyroid hormone (PTH), and 25-hydroxy vitamin D3 (25-OH-D3). Following multivariate modeling, multiple factors logistic regression elucidated that high BMD (P < 0.001, OR = 0.089) and high level of serum 25-OH-D3 (P = 0.012, OR = 0.877) were negatively correlated with the cemented vertebra recompression after PVP. Decreased BMD and lower level of serum 25-OH-D3 might be two critical and significant risk factors for the height loss of cemented vertebrae after PVP.


Engineering of graphene quantum dots by varying the properties of graphene oxide for fluorescence detection of picric acid.
The study examines the effect of different forms of graphene oxide (GO) on the synthesis of graphene quantum dots (GQD). GO synthesized at various temperatures i.e. 30, 50, 110 °C possessed different structural and functional properties and was used as a substrate for GQD preparation. Thorough characterization of the GQDs in terms of their structural, morphological, functional, and optical properties was performed. The GQDs exhibited variation in their size and fluorescence properties depending upon the type of GO used. Hydrothermal reduction of GO, prepared at an oxidation temperature of 50 °C (GO-50), minimized the particle size (3.6 nm) and maximized the photoluminescence (PL) intensity and quantum yield (64.8%) of the GQD (GQD-50). GQD-50 was found to detect picric acid (PA) in an aqueous solution via 'turn-off' fluorescence quenching, unlike the other GQDs where the initial precursor is synthesized at 30, 110 °C. Experimental studies summarize that interaction between the fluorophore-quencher resulted in static quenching. The limit of detection was estimated to be 1.2 μM with a detection range of 0-200 μM. The work concludes that optimization of the substrate i.e. GO can result in the development of a simple, non-toxic, cost-effective GQD based sensor for PA detection. The study eliminates the need for doping/functionalization of GQDs as reported previously, and hence finds a promising impact on the development of sensors.


Integration of distributed multi-analyzer monitoring and control in bioprocessing based on a real-time expert system.
A computer system solution for integration of a distributed bioreactor monitoring and control instrumentation on the laboratory scale is described. Bioreactors equipped with on-line analyzers for mass spectrometry, near-infrared spectroscopy, electrochemical probes and multi-array gas sensors and their respective software were networked through a real-time expert systems platform. The system allowed data transmission of more than 1800 different signals from the instrumentation, including signals from gas sensors, electrodes, spectrometer detectors, balances, flowmeters, etc., and were used for processing and carrying out a number of computational tasks such as partial least-square regression, principal component analysis, artificial neural network modelling, heuristic decision-making and adaptive control. The system was demonstrated on different cultivations/fermentations which illustrated sensor fusion control, multivariate statistical process monitoring, adaptive glucose control and adaptive multivariate control. The performance of these examples showed high operational stability and reliable function and meet typical requirements for production safety and quality.


Degenerative spondylolisthesis with an intact neural arch.
Whereas the skeletal, anatomic, and clinical aspects of this condition have been scrutinized in detail, the radiologic changes have received less attention. In this discussion the plain film changes are briefly reviewed, and emphasis is directed toward the myelographic manifestations that reflect intraspinal and intraforaminal instrusions and their clinical sequelae.


Two novel HLA-A alleles, HLA-A*03:399 and -A*24:17:01:02, detected in inhabitants from the island of Crete
Characterization of two novel HLA-A alleles in two Greek individuals of Cretan origin.


Plasma concentrations of vasoactive intestinal polypeptide in severely burned patients: influence of enteral nutrition.
Plasma vasoactive intestinal polypeptide (VIP) concentrations were measured at different days after burn injury. A significant decrease in VIP levels was observed on days 7 and 10. The influence of enteral nutrition was also investigated: a rise in plasma polypeptide levels was found at 60 min after nutrition restart on days 4 and 7 after injury. In burn patients, VIP may be involved in the multiple metabolic and hormonal responses which lead to an increase in the hypercatabolic state. The decrease in these polypeptide values should reflect enhanced utilisation or complex hormonal regulation. After enteral nutrition, the stimulation of VIP secretion disappeared after day 7 after burn injury. This phenomenon is probably mediated by a process of adaptation to continuous enteral nutrition.


Molecular cloning and characterization of a laccase gene from the basidiomycete Fome lignosus and expression in Pichia pastoris.
A cDNA encoding for a laccase was isolated from the white-rot fungus Fome lignosus by RT-PCR. It contained an open reading frame of 1,557 bp. The deduced mature protein consisted of 497 amino acids and was preceded by a signal peptide of 21 amino acids. The genomic DNA of the laccase, containing 11 introns, was cloned by PCR. The cDNA was cloned into the vectors pGAPZalphaA and pGAPZA, and expressed in the Pichia pastoris GS115. Laccase-secreting transformants were selected by their ability to oxidize the substrate 2'2-azinobis-(3-ethylbenzthiaoline-6-sufonic acid) (ABTS). The laccase activity obtained with the native signal peptide was found to be fivefold higher than that obtained with the alpha-factor secretion signal peptide. The presence of 0.4 mM copper was necessary for optimal activity of the enzyme. The highest activity value reached 9.03 U ml(-1), and the optimal secreting time was 2~3 days at 20 degrees C. The crude laccase was stable in a pH range from 6.0 to 10.0 and at temperatures lower than 30 degrees C in pH 4.5 for 24 h. The molecular mass of the enzyme was estimated to be 66.5 kDa by SDS-PAGE. The optimum pH and temperature were 2.4 and 55 degrees C. The Km and Vmax values for ABTS were 177 microM and 23.54 micromol min(-1) respectively. The extent of glycosylation of the purified enzyme was 58.6%.


Isoenzyme studies in human leukemia-lymphoma cells lines--II. Acid phosphatase.
This report describes the qualitative acid phosphatase (acP) isoenzyme profiles detected in permanent human hematopoietic cell lines. The acP activity was separated into its isoenzymes by isoelectric focusing on horizontal thin-layer polyacrylamide gels. The pattern of acP isoenzyme was investigated in a total of 86 cell lines. These cell lines were classified into five groups on the basis of their phenotypes characterized in the multiple marker analysis: 74 leukemia-lymphoma cell lines (26 T-, 34 B-, 6 myelomonocytic, 8 Non-T, Non-B cell lines) and 12 so-called 'normal' Epstein-Barr virus transformed B-lymphoblastoid cell lines. Their immunological features had been analysed in detail by use of a large panel of poly- and monoclonal antibodies which led to a further subclassification into stages of differentiation. A progressive increase in number and staining intensity of the isoenzymes which paralleled the expression of surface markers at different stages of differentiation along their developmental pathway was seen in the T- and B-leukemia-lymphoma cell lines. Some cell lines whose isoenzyme profiles did not correspond to the stage of differentiation as evidenced by surface antigen analysis might represent good examples of deranged gene expression in otherwise normally programmed malignant cells, i.e. in our study a mismatch between the isoenzymatic and immunological phenotypes. The tartrate-resistant isoenzyme was detected in 9 out of 74 leukemia-lymphoma cell lines (4 T-, 2 B-, 1 myelomonocytic, 2 Non-T, Non-B cell lines) and in 10 out of 12 normal B-lymphoblastoid cell lines; the only one studied hairy cell leukemia cell line did not express this isoenzyme. The relative specificity of the tartrate-resistant acP is discussed in detail. No leukemia-lymphoma specific isoenzyme or an additional isoenzyme which was not seen in normal hematopoietic cells could be observed. Nor did we find an isoenzyme or isoenzyme pattern characteristic for a certain cell lineage. This underlines the necessity of a combined analysis using markers from different disciplines in the 'multiple marker analysis' in order to accurately characterize normal and malignant blood cells. Furthermore, our results support the concept of maturation arrest at particular stages of differentiation together with the theory of normal gene expression in leukemic cells equivalent to that in their normal counterparts.


A one-step co-condensation method for the synthesis of well-defined functionalized mesoporous SBA-15 using trimethallylsilanes as organosilane sources.
A new method for the preparation of well-defined functionalized mesoporous SBA-15 has been developed by a one-step co-condensation method using trimethallylsilanes as organosilane sources. This new method enables the incorporation of various bulky organic functional groups with long alkyl chain tethers into the mesoporous silica network.


Scene saliencies in egocentric vision and their creation by parents and infants.
Across the lifespan, humans are biased to look first at what is easy to see, with a handful of well-documented visual saliences shaping our attention (e.g., Itti & Koch, 2001). These attentional biases may emerge from the contexts in which moment-tomoment attention occurs, where perceivers and their social partners actively shape bottom-up saliences, moving their bodies and objects to make targets of interest more salient. The goal of the present study was to determine the bottom-up saliences present in infant egocentric images and to provide evidence on the role that infants and their mature social partners play in highlighting targets of interest via these saliences. We examined 968 unique scenes in which an object had purposefully been placed in the infant's egocentric view, drawn from videos created by one-year-old infants wearing a head camera during toy-play with a parent. To understand which saliences mattered in these scenes, we conducted a visual search task, asking participants (n = 156) to find objects in the egocentric images. To connect this to the behaviors of perceivers, we then characterized the saliences of objects placed by infants or parents compared to objects that were otherwise present in the scenes. Our results show that body-centric properties, such as increases in the centering and visual size of the object, as well as decreases in the number of competing objects immediately surrounding it, both predicted faster search time and distinguished placed and unplaced objects. The present results suggest that the bottom-up saliences that can be readily controlled by perceivers and their social partners may most strongly impact our attention. This finding has implications for the functional role of saliences in human vision, their origin, the social structure of perceptual environments, and how the relation between bottom-up and top-down control of attention in these environments may support infant learning.


Quantitative determination of tiflorex in human fluids using electron-capture detection.
A procedure is described for the determination of tiflorex and its metabolite nortiflorex in biological specimens. The compounds are converted into their trichoroacetyl derivatives, which are separated on a glass column packed with 3% OV-17 on Gas-Chrom Q, and measured with an electron-capture detector. The mechanism was investigated by gas chromatography-mass spectrometry. The method is rapid, sensitive for concentrations of 1 ng/ml and has been used to measure tiflorex and its metabolite in rat plasma after intravenous administration and in human volunteers after administration by the oral route.


Impacts of agricultural management and climate change on future soil organic carbon dynamics in North China Plain.
Dynamics of cropland soil organic carbon (SOC) in response to different management practices and environmental conditions across North China Plain (NCP) were studied using a modeling approach. We identified the key variables driving SOC changes at a high spatial resolution (10 km × 10 km) and long time scale (90 years). The model used future climatic data from the FGOALS model based on four future greenhouse gas (GHG) concentration scenarios. Agricultural practices included different rates of nitrogen (N) fertilization, manure application, and stubble retention. We found that SOC change was significantly influenced by the management practices of stubble retention (linearly positive), manure application (linearly positive) and nitrogen fertilization (nonlinearly positive) - and the edaphic variable of initial SOC content (linearly negative). Temperature had weakly positive effects, while precipitation had negligible impacts on SOC dynamics under current irrigation management. The effects of increased N fertilization on SOC changes were most significant between the rates of 0 and 300 kg ha-1 yr-1. With a moderate rate of manure application (i.e., 2000 kg ha-1 yr-1), stubble retention (i.e., 50%), and an optimal rate of nitrogen fertilization (i.e., 300 kg ha-1 yr-1), more than 60% of the study area showed an increase in SOC, and the average SOC density across NCP was relatively steady during the study period. If the rates of manure application and stubble retention doubled (i.e., manure application rate of 4000 kg ha-1 yr-1 and stubble retention rate of 100%), soils across more than 90% of the study area would act as a net C sink, and the average SOC density kept increasing from 40 Mg ha-1 during 2010s to the current worldwide average of ∼ 55 Mg ha-1 during 2060s. The results can help target agricultural management practices for effectively mitigating climate change through soil C sequestration.


miR-491-5p regulates the susceptibility of glioblastoma to ferroptosis through TP53.
Ferroptosis has excellent potential in glioblastoma (GBM) therapy. In this study, we attempted to explore the effect of miR 491-5p on ferroptosis in GBM. In this study, publicly available ferroptosis-related genome maps were used to screen genes upregulated in GBM and their target genes. The Spearman correlation coefficient was applied to analyze the correlation between the tumor protein p53 gene (TP53) and miR-491-5p. The expressions of miR-491-5p and TP53 were determined. The protein abundances of the TP53-encoded factors p53 and p21 were measured. Cell proliferation, migration and invasion were assessed. We pretreated U251MG cells and GBM mice with a ferroptosis inducer (erastin). The mitochondrial state was observed. The contents of reactive oxygen species (ROS), total Fe and Fe2+ were calculated. The level of TP53 was significantly increased in GBM and negatively correlated with miR-491-5p. miR-491-5p overexpression promoted U251MG cell proliferation, migration and invasion and interfered with the p53/p21 pathway. TP53 supplement reversed the effects of miR-491-5p. U251MG cells and GBM mice exhibited significant accumulations of ROS and iron. Erastin promoted the expression of TP53. Inhibition of TP53 reversed erastin-induced physiological phenotypes. Moreover, miR-491-5p overexpression caused a decrease in the number of damaged mitochondria and the contents of ROS, total Fe and Fe2+. TP53 supplement disrupted miR-491-5p-repressed ferroptosis. Erastin could inhibit GBM growth, and miR-491-5p overexpression impeded the therapeutic effect of erastin. Our findings reveal the functional diversity of miR-491-5p in GBM and suggest that miR-491-5p/TP53 signaling hinders the sensitivity of GBM to ferroptosis through the p53/p21 pathway.


Shoot regeneration and somatic embryogenesis from needles of redwood (Sequoia sempervirens (D.Don.) Endl.).
A rapid and effective system of somatic embryogenesis and organogenesis from the in vitro needles of redwood (Sequoia sempervirens (D.Don.) Endl.) had been established. The influences of plant growth regulators (PGRs) and days of seedlings in vitro on adventitious bud regeneration and somatic embryogenesis were studied. The process of somatic embryo formation was also observed. The results showed that embryogenic callus was induced and proliferated on Schenk and Hildebrandt (SH) medium with BA (0.5 mg/l), KT (0.5 mg/l) and IBA (1.0 mg/l). SH medium containing BA (0.5 mg/l), KT (0.2 mg/l) and IBA (0.2 mg/l) effectively promoted adventitious bud regeneration. The highest frequency (66.3%) of direct somatic embryogenesis was obtained in the combination of BA (0.5 mg/l) and IBA (0.5 mg/l). The optimal days of seedling in vitro for adventitious bud and somatic embryogenesis were 30 days and 30-40 days, respectively. The developments of somatic embryos were similar to that of zygotic embryogenesis. The result of histocytological studies indicated that proteins were gradually accumulated in the process of somatic embryo formation and there were two peaks of starch grains accumulation that one was in the embryogenic callus and the other was in the globular embryos. These results indicated that starch and protein were closely related with the energy supply and the molecular base of somatic embryogenesis, respectively.


SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction.
Development of structure-activity relationship of cyclic guanines I lead us to discovery of a potent and selective series of phosphodiesterase 5 inhibitors 52-59 (IC50=1.3-11.0 nM, PDE6/5=116-600).


Optimization of the separation lactic acid enantiomers in body fluids by capillary electrophoresis.
The optimization of the separation conditions of the two optical isomers of lactic acid by a factorial design is reported. Initially, different chiral selectors were systematically investigated and then a experimental design with three quantitative factors (cyclodextrin concentration and background buffer pH and concentration) were evaluated. Optimal conditions for obtaining a resolution higher than 1.5 were: phosphate buffer 200 mM at pH=6.0 with 413 mM 2-hydroxypropyl-beta-cyclodextrin added (HP-beta-CD), 20 degrees C, -20 kV of applied potential and polyacrylamide-coated capillary. The method was validated for the measurement in plasma and it was applied to the identification of both isomers in body fluids such as urine, amniotic fluid and cerebrospinal fluid. Samples were centrifuged and diluted (1:4) prior to the analysis.


Modeling Instantaneous Firing Rate of Deep Brain Stimulation Target Neuronal Ensembles in the Basal Ganglia and Thalamus.
Deep brain stimulation (DBS) is an effective treatment for movement disorders, including Parkinson disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei-including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr), and ventral intermediate nucleus (Vim)-across different DBS frequencies. Both synthetic and experimental data were used in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work, and the experimental data were provided using single-unit microelectrode recordings (MERs) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr, and Vim-across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies. Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies. The result of our model fitting was in agreement with experimental single-unit MER data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS and to potentially optimize stimulation parameters based on their actual effects on neuronal activity.


Microbial fed-batch production of 1,3-propanediol by Klebsiella pneumoniae under micro-aerobic conditions.
The microbial production of 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae under micro-aerobic conditions was investigated in this study. The experimental results of batch fermentation showed that the final concentration and yield of 1,3-PD on glycerol under micro-aerobic conditions approached values achieved under anaerobic conditions. However, less ethanol was produced under microaerobic than anaerobic conditions at the end of fermentation. The batch micro-aerobic fermentation time was markedly shorter than that of anaerobic fermentation. This led to an increment of productivity of 1,3-PD. For instance, the concentration, molar yield, and productivity of 1,3-PD of batch micro-aerobic fermentation by K. pneumoniae DSM 2026 were 17.65 g/l, 56.13%, and 2.94 g l(-1) h(-1), respectively, with a fermentation time of 6 h and an initial glycerol concentration of 40 g/l. Compared with DSM 2026, the microbial growth of K. pneumoniae AS 1.1736 was slow and the concentration of 1,3-PD was low under the same conditions. Furthermore, the microbial growth in fed-batch fermentation by K. pneumoniae DSM 2026 was faster under micro-aerobic than anaerobic conditions. The concentration, molar yield, and productivity of 1,3-PD in fed-batch fermentation under micro-aerobic conditions were 59.50 g/l, 51.75%, and 1.57 g l(-1) h(-1), respectively. The volumetric productivity of 1,3-PD under microaerobic conditions was almost twice that of anaerobic fed-batch fermentation, at 1.57 and 0.80 g l(-1) h(-1), respectively.


Effect of hyaluronic acid/chondroitin sulfate on healing of full-thickness tendon lacerations in rabbits.
Viscoat, a high-molecular-weight, highly purified hyaluronic acid (HA) and chondroitin sulfate (CS) compound, was instilled around rabbit plantaris tendon following full-thickness laceration and surgical repair. After 3 weeks of immobilization, no significant difference in adhesion strength or tensile strength of the healing tendons existed between Viscoat-treated tendons and controls. This contradicts previous studies which suggest that hyaluronic acid reduces postoperative tendon adhesions. Further studies examining tendon adhesions after less severe degrees of tendon injury and using direct, quantitative measurement techniques are warranted to demonstrate whether HA has a beneficial effect on tendon healing.


Intervention with a humanoid robot avatar for individuals with social anxiety disorders comorbid with autism spectrum disorders.
For some individuals with social anxiety disorders (SAD) comorbid with autism spectrum disorders (ASD), it is difficult to speak in front of others. Herein, we report the case of a patient with SAD comorbid with ASD who could not speak in front of others until she used a humanoid robot as her avatar. During the intervention, her personality changed from shy to outgoing, which is explained by the Proteus effect. These case findings suggest that interventions with a robot avatar might improve the motivation for individuals with SAD comorbid with ASD who cannot speak in front of others to communicate.


Divergent effects of zinc depletion in brain vs non-brain endothelial cells.
Dietary zinc deficiency is common in developing as well as developed countries. Endothelial cells (EC) lining the inner surface of peripheral blood vessels are sensitive to zinc deficiency and lose structural integrity when exposed to culture media low in zinc or to zinc chelators. In contrast, we demonstrate here that human brain microvascular EC (HBMEC), which constitute the blood-brain barrier (BBB), resist zinc depletion and respond by enhancing their barrier function. This response was specific for HBMEC and did not occur in non-brain EC, such as human umbilical vein endothelial cells, human aortic endothelial cells, and human iliac vein endothelial cells. Our results suggest the presence of specific mechanisms to counteract zinc deficiency at the BBB, likely involving HBMEC junctional complexes. Understanding the mechanisms involved in this unique response might provide means to modulate the BBB dysfunction associated with neurological disorders such as stroke, multiple sclerosis, and Alzheimer's disease.


DNA microarray analysis of white adipose tissue from obese (fa/fa) Zucker rats treated with a beta3-adrenoceptor agonist, KTO-7924.
We aimed to examine the effects of KTO-7924 (beta3-adrenoceptor agonist) on lipid metabolism and mRNA expressions in retroperitoneal white adipose tissue (RP WAT) in obese (fa/fa) Zucker rats using DNA microarray. Oral KTO-7924 for 28 days significantly decreased RP WAT weight, plasma triglyceride, free fatty acid, and insulin, and improved insulin resistance in oral glucose tolerance tests. In RP WAT of KTO-7924-treated rats, DNA microarray analysis revealed specifically enhanced mRNA expressions of uncoupling protein 1 (UCP1) and cytochrome c oxidase subunit VIII-H (COX8H), which are reportedly highly expressed in brown adipose tissue (BAT). Since these mRNA expression levels in RP WAT were significantly lower in obese (fa/fa) Zucker rats than in lean Zucker rats, these genes may be important in lipid metabolism. Our results imply that in obese (fa/fa) Zucker rats, continuous stimulation of beta3-adrenoceptors by KTO-7924 causes BAT-like adipocytes to appear in RP WAT, and improves lipid metabolism.


Lower eyelid swelling as a late complication of Bio-Alcamid filler into the malar area.
To report the late complications associated with permanent filler injections into the malar area for rejuvenation. A retrospective case series of three patients who presented with lower eyelid swelling several years following injection of polyalkylimide (Bio-Alcamid) into the malar area. All patients presented with lower eyelid swelling which developed as a result of spontaneous migration of filler to the lower eyelid. Iatrogenic migration of the filler from the lower eyelid following a trial to remove resulted in an abscess formation which further complicated the removal. Lower eyelid swelling may be one of the late complications associated with the permanent fillers into the malar area. An attempt at removal of filler by aspiration or bimanual expression may result in late migration of the product and the development of eyelid swelling.


Functional materials for microscale genomic and proteomic analyses.
The design of functional materials for genomic and proteomic analyses in microscale systems has begun to mature, from materials designed for capillary-based electrophoresis systems to those tailored for microfluidic-based or 'chip-based' platforms. In particular, recent research has focused on evaluating different polymer chemistries for microchannel surface passivation and improved DNA separation matrix performance. Additionally, novel bioconjugate materials designed specifically for electrophoretic separations in microscale channels are facilitating new separation modalities.


Effects of extraneous stimuli on social cue perception in schizophrenia.
Competing hypotheses that explain the effects of emotionally arousing, extraneous auditory stimuli on the social cue perception of schizophrenic patients were examined in this study: (1) extraneous arousing stimuli enhance patients' cue perception; (2) extraneous stimuli distract patients, and cue perception is diminished. Twenty-five patients with DSM-III-R diagnoses of schizophrenia completed a cue-perception task in which half of the videotaped vignettes included in the task were presented with simultaneous extraneous stimuli and half were not. Item difficulty and consistency across extraneous stimuli conditions were matched on standardization and cross-validation samples. Results showed that schizophrenic subjects were significantly more sensitive to cues when exposed to extraneous stimuli, thereby supporting the first hypothesis. This effect was also observed in a subgroup of schizophrenic subjects who demonstrated a distraction decrement on another test of short-term recall. The presence of extraneous stimuli interacted with perception of abstract cues; that is, schizophrenic subjects were particularly better at perceiving abstract cues when extraneous stimuli were presented simultaneously. Future research needs to determine characteristics of extraneous stimuli that enhance cue perception.


Tibialis anterior response to sudden ankle displacements in normal and Parkinsonian subjects.
It is well known that in Parkinsonian subjects with akinesia, reaction times are increased but reflex latencies remain normal. We have attempted to use this knowledge to distinguish between 'reflex' and 'voluntary' components of the electromyographic (EMG) response to ankle displacement. The EMG and torque responses of tibialis anterior (TA) to randomly applied servo-controlled plantar-flexing displacements of the ankle with and without the subject's intentional opposition were examined in 9 Parkinsonian and 9 age-matched normal humans. To obtain a measure of akinesia, the response latency to a visual stimulus was subsequently measured in the same subjects. Three principal findings emerged. (1) The intermediate latency EMG component (PSR) of the response evoked by ankle displacement with the subject instructed to relax was more regularly evoked and of lower threshold in Parkinsonians than in normals. This finding corresponds to the enlarged M2 component in upper limb muscles. However, the facilitation of PSR was not found to be associated with an increase in torque. In fact, the patients did not exhibit more stiffness than normals under our experimental conditions. (2) Mean latency estimate of the PSR was indistinguishable between Parkinsonians and normals. This finding puts the PSR in the nature of a reflex. Indeed, in accordance with reflex behaviour which is proportional to input characteristics, its area increased linearly with increase in the magnitude of displacement velocity. (3) In contrast, the 'late' EMG response (FSR) evoked by opposing sudden ankle displacement exhibited a significantly longer latency in 6 out of 8 Parkinsonians than normals. In the same patients, the EMG response latency to a visual signal was similarly increased. The delay of FSR in akinesia patients thus argued against its being a stereotyped reflex. The result is discussed with reference to the recent finding that preprogrammed responses are delayed in Parkinsonians.


Abolishment of bradykinin-induced calcium oscillations in ras-transformed fibroblasts by the expression of 80 kDa diacylglycerol kinase.
Our previous study showed bradykinin-induced periodic Ca2+ changes (Ca2+ oscillations) in v-Ki-ras-transformed NIH/3T3 (DT) cells in which protein kinase C (PKC) activity is partially down-regulated by a sustained high level of 1,2-diacylglycerol (DAG) [FEBS Lett. (1991) 281, 263-266]. In the present study, DAG kinase with 80 kDa mass (80K DGK) has been successfully transfected in DT cells, which exhibited enhanced cellular DAG kinase activities, decreased cellular DAG contents, and increased PKC activities compared to the control vector-transfected cells. Furthermore, these DGK-transfectants showed strong inhibition in bradykinin-induced Ca2+ oscillations. The results suggest that the sustained DAG increase down-regulates the PKC activity, thereby leading to the induction of Ca2+ oscillations in DT cells.


Retracted: Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells.
[This retracts the article DOI: 10.1155/2013/210604.].


[Recurrent nonparasitic chyluria].
To describe a case of recurrent chyluria and review the diagnostic and therapeutic methods. A case of non parasitic recurrent chyluria is presented. Retrograde pyelography demonstrated pyelolymphatic reflux. The patient presented chemical pyelitis secondary to the contrast medium which caused remission of the condition. Chyluria is uncommon in our setting. Postprandial cystoscopy permits identification of the compromised renoureteral unit and perform pyelic instillation of sclerosing agents. Surgery should be reserved for those cases in whom conservative management has failed.


Highly polymorphic repeat marker within the beta-amyloid precursor protein gene.
We have identified a polymorphic compound dinucleotide repeat sequence in intron 1 of the beta-amyloid precursor protein (APP) gene on chromosome 21. Using polymerase chain reaction (PCR) amplification of the locus, designated APPivs1, we detected 13 alleles in the CEPH family members (heterozygosity = 0.69). Lod score analysis showed complete linkage of the marker to the loci D21S210 and D21221.


Large-scale analysis of MicroRNA expression in motor neuron-like cells derived from human umbilical cord blood mesenchymal stem cells.
Motor neuron diseases such as spinal cord injuries and amyotrophic lateral sclerosis are known as the most common disorders worldwide. Using stem cells (e.g., human umbilical cord blood mesenchymal stem cells) is currently a potent medical approach for modulating the impact of neural damages and regeneration of spinal cord injuries. MicroRNAs (miRNA) are taken into account as principal regulators during differentiation. The miRNAs play a significant role in stem cell self-renewal and fate determination. There are few studies on how miRNAs regulate neural differentiation in stem cells. The purpose of this study is to explore miRNA profiles of CB-MSCs during differentiation into motor neuron-like cells. Human CB-MSCs were isolated and characterized using flow cytometry. Cell differentiation has been induced by combining retinoic acid (RA) and sonic hedgehog (Shh) in a two-step protocol for 14 days. Then, cell differentiation was confirmed by immunocytochemistry and flow cytometry. The miRNA was analyzed using Illumina/Solexa sequencing platform. In this regard, three libraries were prepared to investigate the effect of these two biological morphogens on the miRNA profile of the differentiating cells. These libraries were Control (non-treated CB-MSCs), Test 1 (RA + /Shh +), and Test 2 (RA-/Shh-). Quantitative RT-PCR was employed to verify miRNA expression. CB-MSCs were spindle-shaped in morphology, and they did not express hematopoietic markers. After differentiation, the cells expressed motor neuron markers (i.e., Islet-1, SMI-32, and ChAT) at the protein level after 14 days. The analysis of miRNA sequencing demonstrated a significant up-regulation of miR-9-5p and miR-324-5p in Test 1 (RA + /Shh +). Also, there is a considerable down-regulation of mir-137 and let-7b in Test 2 (RA-/Shh-). These results have been obtained by comparing them with the Control library. Indeed, they were responsible for neuron and motor neuron differentiation and suppression of proliferation in neural progenitor cells. Furthermore, significant up-regulation was detected in some novel microRNAs involved in cholinergic, JAK-STAT, and Hedgehog and MAPK signaling pathways. CB-MSCs are potent to express motor neuron markers. This procedure has been performed by developing a two-week protocol and employing Shh and RA. The miRNA profile analysis showed a significant up-regulation in the expression of some miRs involved in neuron differentiation and motor neuron maturation. MiR-9-5p and miR-324-5p were up-regulated at the early stage of differentiation. Also, miR-137 and miR-let-7b were downregulated in the absence of RA and Shh. Furthermore, several novel miRNAs involved in cholinergic, Hedgehog, MAPK, and JAK-STAT signaling pathways have been detected. However, further studies are still necessary to validate their functions during motor neuron generation and maturation.