The influence of maternally derived antibody on the efficacy of further attenuated measles vaccine.
The natural decline of passively acquired maternal antibody titers and the influence of these antibodies on the efficacy of live, further attenuated measles vaccine were studied in 7 to 12 month old infants. Hemagglutination-inhibition (HI) antibody titers were determined in the pre- and postvaccination sera. HI antibodies at low titers were detected in 20 (46%) of the 43 infants investigated, in five of six infants at seven months and two of nine infants at 12 months of age. The serological conversion rate following vaccination of the infants exhibiting transplacental maternal antibody was as low as 38%, in contrast with 100% sero-conversion of the infants without measurable antibodies of maternal origin. HI antibody titers were low in the infants seven to nine months of age, reflecting poor antibody responses to the administered vaccine. For the 12 month old infants the geometrical mean antibody titer was 1 : 52. It is concluded that transplacental maternal antibody, even at low concentration, inhibits induction of HI antibody in the vaccinees and therefore measles vaccination must be initiated after 12 months of age in order to achieve successful immunization of the children. Infants who receive the vaccine before their first birthday have to be revaccinated at or after 15 months of age.


Visible-Light-Mediated Synthesis of AzaBenzannulated Perylenediimide-Based Light-Harvesting Dyads.
Intramolecular imine photocyclization has been explored for grafting on the bay region of perylenediimide (PDI) different electro- and photoactive chromophores to achieve new AzaBenzannulated-PDI (AzaBPDI) dyads. Triphenylamine (TPA), fluorene (Fl), perylenemonoimide (PMI), and perylenediimide (PDI) units have been successfully assembled to AzaBPDI using this straightforward one-pot synthesis starting from the easily accessible 1-aminoPDI. This original procedure was compared to the well-known Pictet-Spengler reaction and appears to be an attractive alternative in terms of versatility and efficiency with higher yields obtained. The optical and electrochemical properties of these molecular systems demonstrated large absorption capabilities in the visible range, good accepting abilities with low LUMO levels, and efficient electronic interactions between chromophoric units such as energy or electron transfers. In addition, with their large dihedral angle estimated by theoretical calculations, those dyads should present interesting applications in various organic optoelectronic devices. In particular, the PMI-AzaBPDI and PDI-AzaBPDI dyads presenting low LUMO levels, a broad absorption in the visible range, and a twisted conformation make them good candidates as non-fullerene acceptors in organic solar cells.


Polymorphism of the second component of complement (C2) in Graves' disease.
The polymorphism of C2 was studied by isoelectric focussing in 60 patients with Graves' disease and compared to 800 control sera. No difference in gene frequencies was observed.


Changes in luminal flow rate modulate basal and bradykinin-stimulated cell [Ca2+] in aortic endothelium.
Hemodynamic forces influence many endothelial cell functions. The coupling between hemodynamic forces and cell function could be mediated by mechano-sensitive ion channels present in the plasma membrane of endothelial cells. Because one of these channels is permeable to Ca2+, we tested whether hemodynamic forces influence endothelial cell Ca2+ ([Ca2+]i). Bovine aortic endothelial cells were grown inside cylindrical glass tubes, loaded with fura-2, and perfused at different pressures and flow rates on the stage of a fluorescence microscope. Decreasing flow from 110 to 2 ml.min-1 raised [Ca2+]i from 57 +/- 11 to 186 +/- 29 nM (mean +/- SEM, p less than 0.01) by increasing the entry of extracellular Ca2+ into the cytoplasm. Increasing flow from 2 to 110 ml.min-1 transiently decreased [Ca2+]i from 62 +/- 3 to 33 +/- 5 nM (p less than 0.01) apparently due to reduced Ca2+ entry and concomitant extrusion by the plasma membrane Ca(2+)-ATPase. The rise in [Ca2+]i induced by bradykinin was magnified during a decrease in flow; in control cells, 10(-7) M bradykinin increased [Ca2+]i by 162 +/- 26 nM, whereas [Ca2+]i increased 350 +/- 67 nM (p less than 0.05) in cells previously exposed to 110 ml.min-1. These observations suggest that flow-induced changes in [Ca2+]i might be a signal-transduction mechanism for endothelial functions responsive to hemodynamic forces and may also modulate the magnitude of hormonally mediated increases in [Ca2+]i.


Novel glass capillary microfluidic devices for the flexible and simple production of multi-cored double emulsions.
Double emulsions with many monodispersed internal droplets are required for the fabrication of multicompartment microcapsules and tissue-like synthetic materials. These double emulsions can also help to optically resolve different coalescence mechanisms contributing to double emulsion destabilization. Up to date microfluidic double emulsions are limited to either core-shell droplets or droplets with eight or less inner droplets. By applying a two-step jet break-up within one setup, double emulsion droplets filled with up to several hundred monodispersed inner droplets can be achieved. Modular interconnected CNC-milled Lego®-inspired blocks were used to create two separated droplet break-up points within coaxial glass capillaries. Inner droplets were formed by countercurrent flow focusing within a small inner capillary, while outer droplets were formed by co-flow in an outer capillary. The size of inner and outer droplets was independently controlled since the two droplet break-up processes were decoupled. With the developed setup W/O/W and O/W/O double emulsions were produced with different surfactants, oils, and viscosity modifiers to encapsulate 25-400 inner droplets in each outer drop with a volume percentage of inner phase between 7% and 50%. From these emulsions monodispersed multicompartment microcapsules were obtained. The report offers insights on the relationship between the coalescence of internal droplets and their release.


Quantification of motor unit action potential energy.
Motor unit action potentials (MUAPs) recorded by needle electrode reflect the functional state of the motor unit and its force-generating capacity, and are usually described morphologically (e.g. amplitude, duration). However, since the purpose of motor unit activation is force generation, MUAP energy seems a more physically meaningful measurement. MUAPs were obtained by multi-MUAP decomposition of real interference patterns taken from human patients with neurological diseases. The energy content of each MUAP was measured from a time-frequency representation (TFR), specifically the Choi-Williams distribution, and compared with the standard MUAP morphological measure, the Size Index. The sample included normal, neurogenic, and myopathic MUAPs, from 11 patients. There is an exponential distribution of energy within a sample of MUAPs and a strong exponential relationship between the Size Index and MUAP energy was observed. The energy content of a MUAP can be quantified and corresponds very well with the current quantitative standard. Energy is a possible addition to MUAP quantification. MUAPs could be classified as having normal, large (neurogenic), or low (myopathic) energy. MUAP energy has direct physical and physiological meaning that reflects the force-generating capacity of the motor unit. Time-frequency analysis could also be used to study the specific frequency content of MUAPs and the energy of MUAPs within an interference pattern, without the need for decomposition.


Treatment of CLN1 disease with a blood-brain barrier penetrating lysosomal enzyme.
Neuronal ceroid lipofuscinosis type 1(CLN1 disease) is a rare autosomal recessive lysosomal storage disease caused by genetic defects of palmitoyl protein thioesterase-1(PPT1), leading to accumulation of lipofuscin granules in brain and progressive neurodegeneration. Psychomotor regression, seizures, loss of vision, and movement disorder begin in infancy and result in early death. Currently, no disease-modifying therapy is available. We report a 68-month-old boy with CLN1 treated on a compassionate use basis weekly for 26 months with a PPT1 enzyme fused to an anti-insulin receptor antibody (AGT-194), thereby enabling penetration of the blood-brain barrier (BBB). During treatment, no side effects were observed, while seizure frequency decreased, life quality improved, and the boy's general condition remained stable. This case documents for the first time that treatment of CLN1 is principally feasible by an intravenous BBB penetrating enzyme replacement therapy using PPT1 fused with the human insulin receptor. Monitoring of side effects raised no unacceptable or unexpected safety concerns.Observed improvement of life quality related to ameliorated epilepsy control raises hope that further robust clinical trials including patients in earlier stages of disease will show positive results.


ω-6 (18:2) and ω-3 (18:3) fatty acids in reconstituted high-density lipoproteins show different functionality of anti-atherosclerotic properties and embryo toxicity.
Among unsaturated fatty acids, epidemiologic studies have demonstrated that ω-6 (linoleic acid) and ω-3 (linolenic acid) fatty acids show different associations with risk of cardiovascular disease (CVD), although its molecular mechanisms remain unclear. To determine why consumption of ω-3 fatty acid is associated with lower risk of CVD, we investigated the biological functions of ω-6 (linoleic acid) and ω-3 (linolenic acid) in reconstituted HDL (rHDL) after encapsulation using human cells and zebrafish embryo. Apolipoprotein A-I (apoA-I) is the principal protein behind the beneficial functions of HDL, which include potent anti-oxidant, anti-inflammatory, and anti-atherosclerotic activities in blood. Several rHDLs were synthesized with apoA-I and different molar ratio of ω-6 or ω-3 fatty acid. Both fatty acids showed similar solubility in rHDL up to a molar ratio of 95:5:1:10 (palmitoyloleoyl phosphatidylcholine:cholesterol:apoA-I:fatty acid). Although both rHDL showed similar structural properties and α-helical contents, ω-6-rHDL showed loss of anti-oxidant ability against LDL oxidation. Uptake of acetylated LDL into macrophages was inhibited by ω-3-rHDL but not ω-6-rHDL, suggesting that ω-6-rHDL has higher pro-atherosclerotic activity. ω-3-rHDL showed more enhanced cholesterol efflux activity with less accumulation of triglyceride in the macrophage. ω-6-rHDL caused more senescence in human dermal fibroblast cells with cytotoxicity, while ω-3-rHDL treatment inhibited the senescence. In zebrafish embryo survivability, ω-3-rHDL-injected embryos showed 86±3% survival, whereas ω-6-rHDL-injected ones showed 72±2% survival as well as an elevated inflammatory response in zebrafish embryos. In conclusion, ω-6-rHDL and ω-3-rHDL show different physiological activities in atherosclerosis, inflammation, and cellular senescence.


Prevalence and factors associated with mercury exposure in riverside communities in the Brazilian Western Amazon.
to verify mercury exposure prevalence and identify its possible associated factors in two riverside communities in the Madeira River basin of the Western Brazilian Amazon. a cross-sectional study comprising 95 children and adolescents. Age cycle, school attendance, Bolsa Família, number of siblings, meals, fish consumption, height by age were measured. Binary logistic regression was used to verify relationships between mercury exposure and its possible associated factors. the general prevalence of mercury exposure was 46.3%; children, 35.4%; and adolescents, 57.4%. Associated factors were fish consumption (aOR=1.84; 95%CI 1.56-2.16), age cycle (aOR=2.50; 95%CI 1.09-5.7), parasites (aOR=1.22; 95%CI 1.02-2.71), and short stature (aOR=1.32; 95%CI 1.05-2.02). mercury exposure prevalence in riverside children and adolescents was considered worrying, with association with fish consumption, adolescence, parasites, and short stature.


A new technique for closure of the uterus at caesarean section.
A new method of closure of the uterus at Caesarean section is described. The technique which comprised suturing the uterine incision in a single layer was employed in 100 patients, in all of whom there was also a valid indication for sterilization. Apart from being simple, safe and effective the main advantage of the technique appeared to be saving operating time. A noteworthy feature was that the incidence of postoperative complications was no higher compared with the standard 3-layer suture of the uterus.


Monitoring of ovulation induction.
The plasma hormonal patterns of the normal menstrual cycle have been reviewed. A consistent cyclic pattern of plasma hormone levels is observed in LH, FSH, estrogens, and progestins in the menstrual cycle. Other plasma hormones, such as ACTH, growth hormone, TSH, and PRL, as well as androgens and corticosteroids, fluctuate throughout the menstrual cycle without any consistent pattern during the ovulatory cycle. FSH, LH, E2, E1, P, T, and A levels during the induced ovulatory cycle are presneted for comparison. In the gonadotropin-induced ovulatory cycle most hormones behave in a manner similar to that in the normal ovulatory cycle, except for FSH levels, which rise continuously throughout the follicular phase of the cycle. Following ovulation in the gonadotropin-induced cycle, T rises above normal levels. Early in the clomiphene-induced ovulatory cycle, unlike the normal cycle, LH is distinctly elevated. Levels of both LH and FSH in the rest of the cycle simulate those in the normal cycle. However, T and A levels rise from the very beginning of clomiphene therapy and continue to rise throughout the clomiphene-induced ovulatory cycle. Levels of E and P are higher than in the normal ovulatory cycle, but a similar pattern is preserved. Because of the potential dangers of gonadotropin therapy, monitoring by frequent examination and laboratory tests is required. E monitoring is mandatory to evaluate follicular maturation, to time hCG administration, and to minimize hyperstimulation. Cervical mucus is an unreliable parameter for monitoring gonadotropin therapy alone. In addition to cervical mucus, plasma or urinary E should be monitored regularly. Clomiphene therapy is less dangerous than gonadotropin therapy. Because of its lesser risk, monitoring is rarely performed during clomiphene use. An active monitoring approach has been described. While this approach may not necessarily improve the outcome of clomiphene therapy, it may hasten the process of selecting the appropriate dose. Although other ovulation-inducing agents are available, their use is rarely associated with serious medical complications, and monitoring would seem unnecessary.


Emergency of fungemia cases caused by fluconazole-resistant Candida auris in Beijing, China.
We describe the microbiological characterization and clinical presentation of two fungemia cases caused by fluconazole-resistant Candida auris in neonatal intensive care unit of a hospital in Beijing, China. We advocate for the need of guidelines or recommendations to improve identification, surveillance, and implementation of infection control measures in Chinese hospitals.


Design and Validation of Site-Specifically Labeled Single-Domain Antibody-Based Tracers for in Vivo Fluorescence Imaging and Image-Guided Surgery.
Near-infrared fluorescence molecular imaging has become an established preclinical technique to investigate molecular processes in vivo and to study novel therapies. Furthermore, fluorescence molecular imaging is gaining significant interest from clinicians as an intra-operative guidance tool. This technique makes use of targeted fluorescent tracers as contrast agents that recognize specific biomarkers expressed at the site of disease. Single-domain antibodies have shown to possess excellent properties for in vivo imaging in comparison to conventional antibodies. In this chapter, we describe a method for site-specific conjugation of a near-infrared fluorophore to single-domain antibodies by exploiting cysteine-maleimide chemistry. As opposed to random conjugation, site-specific conjugation results in a homogenously labeled fluorescent tracer and avoids inference with antigen binding.


Optimization of treatment with interferon beta in multiple sclerosis. Usefulness of automatic system application criteria.
A software based tool has been developed (Optem) to allow automatize the recommendations of the Canadian Multiple Sclerosis Working Group for optimizing MS treatment in order to avoid subjective interpretation. Treatment Optimization Recommendations (TORs) were applied to our database of patients treated with IFN beta1a IM. Patient data were assessed during year 1 for disease activity, and patients were assigned to 2 groups according to TOR: "change treatment" (CH) and "no change treatment" (NCH). These assessments were then compared to observed clinical outcomes for disease activity over the following years. We have data on 55 patients. The "change treatment" status was assigned to 22 patients, and "no change treatment" to 33 patients. The estimated sensitivity and specificity according to last visit status were 73.9% and 84.4%. During the following years, the Relapse Rate was always higher in the "change treatment" group than in the "no change treatment" group (5 y; CH: 0.7, NCH: 0.07; p < 0.001, 12 m - last visit; CH: 0.536, NCH: 0.34). We obtained the same results with the EDSS (4 y; CH: 3.53, NCH: 2.55, annual progression rate in 12 m - last visit; CH: 0.29, NCH: 0.13). Applying TOR at the first year of therapy allowed accurate prediction of continued disease activity in relapses and disability progression.


Potential identification of the O2-sensitive K+ current in a human neuroepithelial body-derived cell line.
Whole cell recording of H-146 cells revealed that the outward K+ current was completely inhibited by quinidine (IC50 approximately 17 microM). In contrast, maximal concentrations of 4-aminopyridine (4-AP; >/=10 mM) reversibly blocked only approximately 60% (IC50 approximately 1.52 mM). Ten millimolar 4-AP had no effect on the inhibition by hypoxia, which reduced current density from approximately 27 to approximately 13 pA/pF, whereas 1 mM quinidine abolished the hypoxic effect. In current clamp, 10 mM 4-AP depolarized the cell by approximately 18 mV and hypoxia caused further reversible depolarization of approximately 4 mV. One millimolar quinidine collapsed the membrane potential and abrogated any further hypoxic depolarization. RT-PCR revealed expression of the acid-sensitive, twin P domain K+ channel TASK but not of TWIK, TREK, or the known hypoxia-sensitive Kv2.1, which was confirmed by sequencing and further PCR with primers to the coding region of TASK. However, a reduction in extracellular pH had no effect on K+ current. Thus, although the current more closely resembles TWIK than TASK pharmacologically, structurally the reverse appears to be true. This suggests that a novel acid-insensitive channel related to TASK may be responsible for the hypoxia-sensitive K+ current of these cells.


Emerging Trends: Primary Care Networks Addressing the Workforce Crisis.
To build a resilient, high-performing primary care infrastructure for North Carolina, primary care networks and policymakers should align efforts to create pathways for students, trainees, and new physicians to thrive in primary care. We describe the shifting primary care landscape, current workforce initiatives, and policy options for achieving this goal.


Green synthesis of bacterial cellulose via acetic acid pre-hydrolysis liquor of agricultural corn stalk used as carbon source.
Herein, bacterial cellulose (BC) was synthesized by acetobacter xylinum via organic acid pre-hydrolysis liquor of agricultural corn stalk used as carbon source. Acetic acid was applied to pretreat the corn stalk, then, the prehydrolysate was detoxified by sequential steps of activated carbon and ion exchange resin treatment prior to use as carbon source to cultivate acetobacter xylinum. Moreover, the recovery of acetic acid was achieved for facilitating the reduction of cost. The results revealed that the combination method of detoxification treatment was very effective for synthesis of BC, yield could be up to 2.86g/L. SEM analysis showed that the diameter size of BC between 20 and 70mm. In summary, the process that bacterial cellulose was biosynthesized via prehydrolysate from agricultural corn stalk used as carbon source is feasible, and the ability to recover organic acid make it economical, sustainable and green, which fits well into the biorefinery concept.


Partners in School: Optimizing Communication between Parents and Teachers of Children with Autism Spectrum Disorder.
Partners in School is a consultation model with the goal of enhancing communication between two of the most important stakeholders in children's lives - parents and teachers. Using a single-group pre-post design, this preliminary study examined the effect of Partners in School on parent-teacher communication outcomes and the factors associated with these outcomes. Participants were 26 teachers and 49 parents of children with autism spectrum disorder (ASD). Parents and teachers completed surveys before and after participating in Partners in School. Teachers reported an increase in their communication to parents. However, parents did not report an increase in their communication to teachers. Teachers' self-efficacy, expectations, and intervention fidelity were associated with increased communication to parents. Parental self-efficacy and teacher experience were associated with parents' reports of communication to teachers. Our findings suggest that family-school consultation services may be used to enhance teachers' communication with parents.


An eight week school-based intervention with circuit training improves physical fitness and reduces body fat in male adolescents.
School-based intervention programs have been found to effectively improve various fitness and health parameters. However, only few studies so far examined the effect of circuit training in school environment during physical education (PE) classes. The aim of the current study was to examine the effects of an eight-week circuit training on physical fitness and body fat in male adolescents. Thirty nine, 16-year old male high-school students participated in the current study. The students were randomly assigned to intervention and control groups. The intervention period lasted eight weeks and consisted of two circuit training sessions per week performed during regular PE classes. Total body fat was calculated by using bioelectrical impedance analysis. Physical fitness parameters such as cardiorespiratory fitness, flexibility, jumping ability and isometric arm strength were assessed through a battery of field tests. Finally, resting heart rate and blood pressure levels were assessed with an automatic monitor. By the end of the intervention period, total body fat and resting systolic blood pressure were significantly lower while cardiorespiratory fitness was significantly improved in the circuit training group only (P<0.05). In the control group Body Mass Index and total body fat percentage were significantly increased when compared pre- and post-intervention period (P<0.05). Eight weeks of circuit training during PE classes appeared to be effective in improving various physical fitness parameters and reducing fatness in male adolescents.


Impact of an invasive weed, Parthenium hysterophorus, on a pasture community in south east Queensland, Australia.
Parthenium weed is a highly invasive alien species in more than 40 countries around the world. Along with severe negative effects on human and animal health and crop production, it also causes harm to ecosystem functioning by reducing the native plant species biodiversity. However, its impacts on native plant species, especially in pasture communities, are less known. Given parthenium weed causes substantial losses to Australian pastures' productivity, it is crucial to estimate its impact on pasture communities. This study evaluates the impact of parthenium weed upon species diversity in a pasture community at Kilcoy, south east Queensland, Australia. Sub-sites containing three levels of parthenium weed density (i.e. high, low and zero) were chosen to quantify the above- and below-ground plant community structure. Species richness, diversity and evenness were all found to be significantly reduced as the density of parthenium weed increased; an effect was evident even when parthenium weed was present at relatively low densities (i.e. two plants m-2). This trend was observed in the summer season as well as in winter season when this annual weed was absent from the above-ground plant community. This demonstrates the strong impact that parthenium weed has upon the community composition and functioning throughout the year. It also shows the long-term impact of parthenium weed on the soil seed bank where it had displaced several native species. So, management options used for parthenium weed should also consider the reduction of parthenium weed seed bank along with controlling its above-ground populations.


Average treatment effect of facility hepatopancreatobiliary malignancy case volume on survival of patients with nonoperatively managed hepatobiliary malignancies.
Surgical volume-outcome relationships have been described for a variety of procedures. There is scant literature on total institutional volume and outcomes in patients who are nonoperatively managed. We examined the average treatment effect of total hepatopancreatobiliary malignancy case volume on survival outcomes of patients with nonresected hepatobiliary malignancies. We identified patients with hepatopancreatobiliary malignancies [pancreatic adenocarcinoma, pancreatic neuroendocrine neoplasms, hepatocellular carcinoma, biliary tract cancers] within the National Cancer Database (2004-2018). We determined percentile thresholds based on the total annual hepatopancreatobiliary malignancy case volume. We then identified nonoperatively managed patients with hepatocellular carcinoma or biliary tract cancers. We used inverse probability-weighted Cox regression to estimate the effect of facility volume on overall survival. We identified 710,988 patients with hepatopancreatobiliary malignancies. Total annual hepatopancreatobiliary malignancy case volume of 32, 71, and 177 cases/year corresponded to the 25th, 50th, and 75th percentiles. A total of 96,420 with hepatocellular carcinoma and 52,627 patients with biliary tract cancers were managed nonoperatively. In patients with hepatocellular carcinoma or biliary tract cancer, treatment at ≥25th, ≥50th, and ≥75th percentile facilities was associated with improved median, 1-, 2-, and 3-year overall survival compared with treatment at lower-percentile facilities. On inverse probability-weighted Cox analysis, treatment at higher-percentile facilities resulted in a lower hazard of death. Consistent findings were observed in patients with early or intermediate/advanced hepatocellular carcinoma or metastatic biliary tract cancers. Patients with nonoperatively managed hepatocellular carcinoma or biliary tract cancer who receive treatment at higher-volume facilities have improved survival outcomes. These data suggest regionalization of care for patients with hepatocellular carcinoma or biliary tract cancer to high-volume centers may improve survival.


The fundamental theorem of natural selection in optimization and games.
The Fisher's fundamental theorem of natural selection (FTNS) is a matter of longstanding debate in the community of mathematical biologists. Many researchers proposed different clarifications and mathematical reconstructions of the Fisher's original statement. The present study is motivated by our opinion that the controversy can be resolved by examining the Fisher's statement within the framework of two mathematical theories that are inspired by the Darwinian formalism: evolutionary game theory (EGT) and evolutionary optimization (EO). We present four rigorous formulations (some of them previously reported) of FTNS in four different setups that come from EGT and EO. Our study demonstrates that FTNS in its original form is correct only in certain setups. In order to be recognized as a universal law, the Fisher's statement should be: (a) clarified and completed and (b) relaxed by replacing the words "is equal to" with "does not exceed". Moreover, the real meaning of FTNS can be best understood from the information-geometric point of view. Such an approach shows that FTNS imposes an upper geometric bound on information flows in evolutionary systems. In this light, FTNS appears to be a statement about the intrinsic time scale of an evolutionary system. This leads to a novel insight: FTNS is an analogue of the time-energy uncertainty relation in physics. This further emphasizes a close relation with results on speed limits in stochastic thermodynamics.


Effect of ticagrelor versus prasugrel on platelet reactivity: a meta-analysis.
Whether ticagrelor is superior to prasugrel in inhibiting platelet reactivity (PR) has remained unclear, possibly because different test methods have been used to determine this. Therefore, using a different test method, we performed a meta-analysis comparing the effects of ticagrelor and prasugrel on PR. PubMed, Embase, Web of Science, and Google Scholar were searched - without language restrictions (last updated on 26 February 2017) - for randomized trials comparing the effects of prasugrel with those of ticagrelor in patients with coronary artery disease. Selected studies were chosen for pooled analysis according to the inclusion and exclusion criteria. Data are presented as mean difference (MD) and 95% confidence interval. For the loading dose, using the VerifyNow-P2Y12 (VN) test, the PR was similar for both the prasugrel and ticagrelor groups [MD=10.80 (-9.81-31.40), P=0.30]. Using the vasodilatorstimulated phosphoprotein test, the PR was also similar for both the ticagrelor and prasugrel groups [MD=-2.87 (-6.35-0.60), P=0.10]. For the maintenance dose, using the VN test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-43.37 (-60.53 to -26.21), P<0.01]. Finally, using the vasodilator-stimulated phosphoprotein test, the PR was lower in the ticagrelor group than in the prasugrel group [MD=-9.23 (-15.82 to -2.64), P<0.01]. There was no difference between ticagrelor and prasugrel in terms of PR under the loading dose, but ticagrelor had a lower degree of PR under the maintenance dose. The results were not affected by the different PR test methods.


Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats.
In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.


Editor's Choice - Two Year Results of the Randomised DISCOVER Trial Comparing Covered Versus Bare Metal Stents in the Common Iliac Artery.
It has been suggested that covered stents (CS) may lower restenosis rates compared with bare metal stents (BMS) after endovascular treatment of the common iliac artery. This trial aimed to provide additional evidence on the efficacy of CS vs. BMS in the common iliac artery. This multicentre, randomised, single blind controlled superiority trial compared balloon expandable CS and balloon expandable BMS for advanced atherosclerotic lesions in the common iliac artery; this was defined as a stenosis > 3 cm in length or occlusion. The primary end point was freedom from binary restenosis after two years of follow up. The study was conducted according to the principles of the Declaration of Helsinki (version: October 2008) and registered with the Dutch Trial register (NTR3381). One hundred and seventy-four limbs were included between 2012 and 2019 with 87 limbs in each group. Six patients crossed over from the BMS group to the CS group but were analysed according to an intention to treat principle. Freedom from binary restenosis after two years of follow up was 84.7% (95% CI 76.7 - 92.7%) in the BMS group and 89.1% (95% CI 82.4 - 95.8%) in the CS group (p = .40). Freedom from occlusion was 95.0% (95% CI 90.3 - 95.7%) in the BMS group and 96.4% (95% CI 92.5 - 100%) in the CS group (p = .66). Freedom from target lesion revascularisation was 91.1% (95% CI 84.8 - 97.3%) and 95.2% (95% CI 90.7 -99.7%), respectively (p = .31). Technical success, complications, haemodynamic success, and clinical success were also comparable between both groups. Per-protocol analysis did not affect the outcomes of the study. No difference was found between balloon expandable CS and BMS for treating advanced atherosclerotic lesions of the common iliac artery.


[Development and application of the facial soft tissue 3D measuring system].
To combine measurement and image technology as an objective means to help prosthodontists provide better service. The system was developed by consisting of two CCD cameras, real time hardware for the recognition of markers and software for the 3D reconstruction. It allowed efficient, direct and noninvasive calculation of the 3D liner and angular measurements of the human face. This system is a useful way to get 3D information of the human face. It will be a good supplement to the classic cephalometric analyses.


The acquired immunodeficiency syndrome: an ultrastructural study.
Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers.


Psychosocial, health and demographic characteristics of quality of life among patients with acute myeloid leukemia and malignant lymphoma who underwent autologous hematopoietic stem cell transplantation.
This study evaluated the effect of selected psychosocial, health and demographic characteristics of quality of life (QOL) among patients treated with autologous hematopoietic stem cell transplantation (HSCT). This was a retrospective study at Charles University Hospital, Hradec Kralove. The Czech version of the international generic European Quality-of-Life questionnaire (EQ-5D) was applied to evaluate QOL among patients with acute myeloid leukemia (AML) and malignant Hodgkins and non-Hodgkins lymphoma (ML). The total number of respondents was 36: 12 with AML (seven males and five females) and 24 with ML (11 males and 13 females). The mean age of AML respondents was 46 years and the mean age of ML respondents was 44.5 years. Age, smoking status and education level had statistically significant effects on QOL among AML respondents (p < 0.05), and age had a statistically significant effect on QOL among ML respondents (p < 0.05). The overall QOL among AML and ML respondents was generally good: the mean EQ-5D score among AML respondents was 71.5% and among ML respondents it was 82.7%. The QOL among AML and ML respondents treated with autologous HSCT was good. However, patients more than 50 years old, smokers and patients with lower education levels presented worse QOL. These findings need to be better evaluated in longitudinal studies, using large samples.


Autoantibodies against alternative complement pathway proteins in renal pathologies.
Complement system activation plays an important role in several renal pathologies, including antibody-mediated glomerulonephritis, ischaemia-reperfusion injury of trasplanted kidneys or renal allograft rejection. Besides these conditions, alternative pathway abnormalities are directly involved in the pathogenesis of C3 glomerulopathies and atypical haemolytic uraemic syndrome. These abnormalities may be inherited or acquired, the latter as autoantibodies directed against the various components and regulators of the alternative complement pathway. The functional consequences of some of these antibodies and their association with these conditions are well known, whereas for other antibodies only isolated cases have been reported. This article describes the autoantibodies that target the alternative complement pathway proteins, their characteristics and their clinical relevance in renal pathologies.


Ovalbumin sensitization and challenge increases the number of lung cells possessing a mesenchymal stromal cell phenotype.
Recent studies have indicated the presence of multipotent mesenchymal stromal cells (MSCs) in human lung diseases. Excess airway smooth muscle, myofibroblasts and activated fibroblasts have each been noted in asthma, suggesting that mesenchymal progenitor cells play a role in asthma pathogenesis. We therefore sought to determine whether MSCs are present in the lungs of ovalbumin (OVA)-sensitized and challenged mice, a model of allergic airways disease. Balb/c mice were sensitized and challenged with PBS or OVA over a 25 day period. Flow cytometry as well as colony forming and differentiation potential were used to analyze the emergence of MSCs along with gene expression studies using immunochemical analyses, quantitative polymerase chain reaction (qPCR), and gene expression beadchips. A CD45-negative subset of cells expressed Stro-1, Sca-1, CD73 and CD105. Selection for these markers and negative selection against CD45 yielded a population of cells capable of adipogenic, osteogenic and chondrogenic differentiation. Lungs from OVA-treated mice demonstrated a greater average colony forming unit-fibroblast (CFU-F) than control mice. Sorted cells differed from unsorted lung adherent cells, exhibiting a pattern of gene expression nearly identical to bone marrow-derived sorted cells. Finally, cells isolated from the bronchoalveolar lavage of a human asthma patient showed identical patterns of cell surface markers and differentiation potential. In summary, allergen sensitization and challenge is accompanied by an increase of MSCs resident in the lungs that may regulate inflammatory and fibrotic responses.


Inline electron holography and VEELS for the measurement of strain in ternary and quaternary (In,Al,Ga)N alloyed thin films and its effect on bandgap energy.
We present the use of (1) dark-field inline electron holography for measuring the structural strain, and indirectly obtaining the composition, in a wurtzite, 4-nm-thick InAlGaN epilayer on a AlN/GaN/AlN/GaN multinano-layer heterosystem, and (2) valence electron energy-loss spectroscopy to study the bandgap value of five different, also hexagonal, 20-50-nm-thick InAlGaN layers. The measured strain values were almost identical to the ones obtained by other techniques for similarly grown materials. We found that the biaxial strain in the III-N alloys lowers the bandgap energy as compared to the value calculated with different known expressions and bowing parameters for unstrained layers. By contrast, calculated and experimental values agreed in the case of lattice-matched (almost unstrained) heterostructures.


Some considerations in the measurement of change.
When conducting a study to assess the "gains in ability" or the "shifts in attitudes" of a group of subjects, the researcher must be aware of the presence of measurement error and regression toward the mean and must attempt to minimize and allow for these phenomena. Also of concern are whether the study can be generalized to a larger population and what statistical techniques are appropriate for the conditions of the study and the type of data collected. Educational and psychologic measurement is subject to particular types of error and must be analyzed and interpreted accordingly. The authors discuss and make recommendations regarding these most important considerations.


Redox-Neutral Photocatalytic Radical Cascade Cyclization for the Synthesis of CH2CN/CF2COOEt/CF3-Containing Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-One Derivatives.
A novel method for the synthesis of benzo[4,5]imidazo[2,1-a]isoquinolin derivatives via visible-light-induced radical cascade cyclization is described. By using N-methacryloyl-2-phenylbenzoimidazoles and diverse radical precursors, various benzo[4,5]imidazo[2,1-a]isoquinolin derivatives containing CH2CN/CF2COOEt/CF3 can be formed in good to excellent yields under mild reaction conditions. This method exhibits good functional group tolerance and a wide range of substrate scope.


Two-stage anaerobic membrane bioreactor for the treatment of sugarcane vinasse: assessment on biological activity and filtration performance.
A two-stage submerged anaerobic membrane bioreactor (2-SAnMBR) was designed for the treatment of sugarcane vinasse. For start-up, the flow rate was reduced whenever VFA levels reached critical levels in the methanogenic reactor. After acclimation, the system was operated under a continuous flow. Separation of the stages was observed during the entire period of operation. VFA, COD and DOC levels of raw effluent, acidified effluent and permeate averaged 2141, 3525 and 61 mg VFA L(-1) (as acetic acid), 15727, 11512 and 488 mg COD L(-1), and, 3544, 3533 and 178 mg DOC L(-1), respectively. Overall COD and DOC removal efficiencies of 96.9±0.7% and 95.0±1.1%, respectively, were reached. Methane content of the biogas from the acidogenic and methanogenic reactors ranged 0.1-4.6% and 60.1-70.1%, respectively. Removable fouling strongly affected filtration performance and cake layer formation accounted for most of filtration resistance. Membrane resistance was related to presence of protein-like substances and carbohydrates.


Combined analysis of CSF betaA42 peptide and tau protein and serum antibodies to glycosaminoglycans in Alzheimer's disease: preliminary data.
Neuropathological hallmarks of Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles, containing betaA(42) peptide and tau protein, respectively. Amyloid plaques contain also glycosaminoglycans (GAGs). Whereas cerebrospinal fluid (CSF) levels of betaA(42) peptide and tau protein have been demonstrated as potential markers of Alzheimer's disease (AD), no data are available for GAGs. We determined (Elisa) tau and betaA(42) CSF levels, as well as serum antibodies to GAGs in 9 AD patients, and the values were analyzed in relation to age and severity of the disease. Beta-A42 and tau CSF levels were significantly reduced and increased, respectively, in AD patients when compared to controls, but they did not correlate with the severity of the disease. Despite their role in amyloidogenesis, we did not find evidence for the use of GAGs as diagnostic marker of AD.


Functional consequences of motor unit recruitment order reversals following spinal cord transection in cat.
Motoneuron recruitment order determinations were made for acute, 2-week chronic, and 3-month chronic spinal cats by comparing cutaneous nerve stimulation thresholds for evoking single unit tibialis anterior (TA) electromyogram (EMG) spikes of different sizes. Recruitment order was largely ( approximately 80%) orderly (small spikes recruited at lower stimulus intensities than large spikes) in acute and 3-month chronic spinal animals. However, in 2-week chronic spinal animals recruitment order was reversed, with large units more often recruited at lower stimulus intensities than small units ( approximately 65%). Morphological analyses of TA muscle fibers suggested that fiber size changes were unlikely to account for the dramatic alterations in recruitment order results of the 2-week chronic spinal animals. Additional studies suggested that the recruitment order reversal in the 2-week chronic animals coincided with an enhanced reflex neural output (increased recruitment or reflex gain) for the flexion reflex which compensated for disuse atrophy related decreases in flexor muscle force generation capability in these animals. The data from 2-week chronic spinal animals represent a functionally significant example of deviation from the normal size principle of motoneuron recruitment order as the corresponding reflex gain increases can enhance the rapidity of motor function recovery (standing, locomotion) following spinal injury.


Seas the day: Co-designing immersive virtual reality exergames with exercise professionals and people living with dementia.
Physical activity (PA) is associated with physical and cognitive benefits among people living with dementia or mild cognitive impairment (PLWD/MCI) and is a meaningful activity that can improve their confidence in everyday life. Exercising in virtual reality environments (VR Exergame) is becoming an increasingly feasible and enjoyable way to promote PA and well-being in PLWD/MCI. Although co-design can significantly improve the design of technology, it is rarely done with PLWD/MCI. This study uses participatory design methods and collaborative approaches to involve key stakeholders to develop and test a VR Exergame "Seas the Day", a novel solution targeting PLWD/MCI well-being. A multi-stage, user-centered co-design approach was used to custom-build VR Exergames tailored to the unique needs and abilities of PLWD/MCI based on a first generation of the prototype that was previously developed and tested with PLWD/MCI. This paper describes the next iteration of the prototype. Processes included concept ideation and brainstorming activities, iterative prototyping, and playtesting/input/feedback sessions with key stakeholders (PLWD/MCI, exercise professionals, engineers, VR game designers, content developers). The multidisciplinary and collaborative design process occurred over 15 months (overlapping with COVID-19 pandemic) with 7 PLWD/MCI (6 females; M=81.3 years) and 9 exercise professionals (7 females; M=38.1 years) to date. The game was designed to target movements identified by exercise professionals and researchers (aerobic exercises, range of motion, seated-balance, quick response to stimuli) and is structured in three exercise stages (warm-up, conditioning, cool-down). To ensure safety of participants while using VR headsets, only seated upper-limb exercises were targeted. Stakeholder feedback regarding game mechanics, aesthetics, and visual/auditory cues were gathered during brainstorming and playtesting sessions and implemented into specific game-related scenarios (tai-chi, rowing, fishing). We presented the process, outcomes, and challenges of adopting a participatory/collaborative approach with multiple stakeholder groups to co-design VR Exergames tailored to PLWD/MCI. Next steps will include a mixed-method evaluation of the VR Exergames among community-dwelling older adults and PLWD/MCI in retirement communities and long-term care to evaluate: i) feasibility and acceptability of use, ii) game user experience, iii) barriers/facilitators to uptake of VR Exergames; and iv) inform/validate VR Exergames gameplay metrics reflective of cognitive and motor performance.


IgA pemphigus following COVID-19 vaccination: A case report.
A patient presented with pruritic lesions on their back and leg after COVID-19 vaccination. Biopsy and direct immunofluorescence were consistent with IgA pemphigus-likely caused by the COVID-19 vaccine.


A progressive ratio schedule of self-stimulation testing in rats reveals profound augmentation of d-amphetamine reward by food restriction but no effect of a "sensitizing" regimen of d-amphetamine.
Prior research indicates that psychostimulant-induced sensitization is not expressed in lateral hypothalamic electrical self-stimulation (LHSS)-based measures of drug reward, although the augmenting effect of chronic food restriction is. Neuroadaptations within the brain dopamine system have been identified in both psychostimulant-sensitized and food-restricted animals. Consequently, a variant of the LHSS paradigm in which responding is particularly sensitive to changes in dopaminergic tone may be best suited to detect and compare effects of chronic d-amphetamine and food restriction. Instrumental responding on a progressive ratio (PR) schedule is more sensitive to dopaminergic manipulations than is responding on a continuous reinforcement (CRF) schedule, but has not previously been used to examine chronic psychostimulant and food restriction effects on LHSS-based measures of drug reward. The first aim of this study was to determine whether a regimen of d-amphetamine treatment, that produces locomotor sensitization (5 mg/kg per day x5 days), increases the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The second aim, was to determine whether chronic food restriction produces a marked increase in the reward-potentiating effect of d-amphetamine in the PR LHSS protocol and, if so, whether it is reversible in parallel with body weight recovery when free feeding is restored. Reward-potentiating effects of a challenge dose of d-amphetamine (0.25 mg/kg, IP) were measured in terms of the break point of LHSS responding on a PR schedule of reinforcement, in ad libitum fed and food-restricted rats. A regimen of d-amphetamine treatment that produced locomotor sensitization did not increase the break point for LHSS in the presence or absence of d-amphetamine. Chronic food restriction produced a marked increase in the break point-increasing effect of d-amphetamine (3-fold), which returned to baseline in parallel with body weight recovery over a 4-week period of restored free-feeding. A locomotor-sensitizing regimen of d-amphetamine treatment does not increase the rewarding effect of LH electrical stimulation or the reward-potentiating effect of d-amphetamine in a PR LHSS protocol. The augmenting effect of chronic food restriction on drug reward is mechanistically and functionally different from psychostimulant sensitization and may be controlled by signals associated with adipose depletion and repletion.


Intracerebral gadolinium deposition following blood-brain barrier disturbance in two different mouse models.
To evaluate the influence of the blood-brain barrier on neuronal gadolinium deposition in a mouse model after multiple intravenous applications of the linear contrast agent gadodiamide. The prospective study held 54 mice divided into three groups: healthy mice (A), mice with iatrogenic induced disturbance of the blood-brain barrier by glioblastoma (B) or cerebral infarction (C). In each group 9 animals received 10 iv-injections of gadodiamide (1.2 mmol/kg) every 48 h followed by plain T1-weighted brain MRI. A final MRI was performed 5 days after the last contrast injection. Remaining mice underwent MRI in the same time intervals without contrast application (control group). Signal intensities of thalamus, pallidum, pons, dentate nucleus, and globus pallidus-to-thalamus and dentate nucleus-to-pons ratios, were determined. Gadodiamide complex and total gadolinium amount were quantified after the last MR examination via LC-MS/MS and ICP-MS. Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios showed no significant increase over time within all mice groups receiving gadodiamide, as well as compared to the control groups at last MR examination. Comparing healthy mice with group B and C after repetitive contrast administration, a significant SI increase could only be detected for glioblastoma mice in globus pallidus-to-thalamus ratio (p = 0.033), infarction mice showed no significant SI alteration. Tissue analysis revealed significantly higher gadolinium levels in glioblastoma group compared to healthy (p = 0.013) and infarction mice (p = 0.029). Multiple application of the linear contrast agent gadodiamide leads to cerebral gadolinium deposition without imaging correlate in MRI.


In situ fate and partitioning of waterborne perfluoroalkyl acids (PFAAs) in the Youngsan and Nakdong River Estuaries of South Korea.
Concentrations, distributions, fate, and partitioning of perfluoroalkyl acids (PFAAs) were investigated in surface water (n=34) collected from the Youngsan and Nakdong River Estuaries of South Korea. Thirteen individual PFAAs in water and suspended solids (SS) were quantified by use of HPLC-MS/MS. PFAAs were detected in all samples, which indicated that they were widely distributed in the study area. Greater concentrations of PFAAs were found at some inland sites which seemed to be affected by direct input from point sources, such as wastewater treatment plants, and/or indirect diffusive sources, such as surface runoff. Spatial distributions of PFAAs in estuaries along transects toward the open sea demonstrated that these chemicals were transported to the outer region primarily by water discharged during the rainy season. Field-based partition coefficients (K(d)) for long-chain PFAAs (C≥8) were significantly correlated with salinity (r(2)=0.48 to 0.73, p<0.01); K(d) values increased exponentially as a function of salinity. Due to the 'salting-out' effect, PFAAs were largely scavenged by adsorption onto SS and/or sediments in estuarine environments. In addition, values for K(d) of those PFAAs were directly proportional to the number of carbon atoms in the PFAAs. Salting constants of selected PFAAs were notably greater than those of other environmental organic contaminants, which indicated that adsorption of PFAAs is largely associated with salinity. Overall, the results of the present study will provide better understanding of the fate and transport of PFAAs in the zone of salinity boundary that can be used for developing fate models of PFAAs in the coastal marine environment.


The association between SBP and mortality risk differs with level of cognitive function in very old individuals.
Cognitive impairment and dementia are highly prevalent in very old populations. Cardiovascular disease is a common cause of death in people with dementia.This study investigated whether the association of blood pressure (BP) with mortality differed with respect to mini-mental state examination (MMSE) score in a representative sample of very old individuals. The sample consisted of 1115 participants aged 85, 90, and at least 95 years from the Umeå85+/GErontological Regional DAtabase cohort study. The main outcome was all-cause mortality within 2 years according to BP and MMSE score, using Cox proportional-hazard regression models adjusted for sociodemographic and clinical characteristics associated with death. Mean age, MMSE score, and SBP and DBP were 89.4 ± 4.6 years, 21.1 ± 7.6, 146.1 ± 23.4 mmHg, and 74.1 ± 11.7 mmHg, respectively. Within 2 years, 293 (26%) participants died. BP was not associated independently with mortality risk, except among participants with MMSE scores of 0-10 among whom mortality risk was increased in association with SBP at least 165 mmHg and 125 mmHg or less, compared with 126-139 mmHg (adjusted hazard ratio 4.54, 95% confidence interval = 1.52-13.60 and hazard ratio 2.23, 95% confidence interval = 1.12-4.45, respectively). In age and sex-adjusted analyses, SBP 125 mmHg or less was associated with increased mortality risk in participants with MMSE scores at least 18. In people aged at least 85 years, the association of SBP with mortality appears to differ with respect to MMSE score. Very old individuals with very severe cognitive impairment and low or high BP may have increased mortality risk.


The limping child.
A child who limps or complains of limb pain presents a diagnostic challenge for the emergency physician. Fortunately, only a few causes require emergency treatment. This article provides the physician with a systematic approach for evaluating these patients. Detailed discussion is provided for some of the more prevalent, urgent, and age-specific diagnoses of limb pain and limping.


Decreased tissue inhibitor of metalloproteinase-2/matrix metalloproteinase ratio in the acute phase of aortic dissection.
Aortic dissection is characterized by fragility of the tunica media, and matrix metalloproteinases (MMPs) are enzymes that degrade the extracellular matrix of the aorta. This study examines MMPs in patients with acute aortic dissection (AAD) in an attempt to elucidate the mechanisms of their actions. Enzyme-linked immunosorbent assays were used to measure the quantification of MMP-2, MMP-9, and the tissue inhibitor of metalloproteinase (TIMP)-2 in 30 patients with AAD, 12 patients with abdominal aortic aneurysm (AAA), and 16 control (CON) patients who underwent coronary artery bypass grafting. MMP-2 and TIMP-2 were significantly lower in the AAD group than in the CON group, at 36 +/- 19 vs 58 +/- 30 (P < 0.01) and at 21 +/- 25 vs 216 +/- 130 (P < 0.001), respectively. The TIMP-2/MMP-2 ratio was 3.7 +/- 1.7 in the CON group and 0.9 +/- 0.8 in the AAD group (P < 0.001 vs CON), and the TIMP-2/MMP-9 ratio was 200 +/- 170 in the CON group and 37 +/- 80 in the AAD group (P < 0.001 vs CON). Low TIMP-2/MMP-2 and TIMP-2/MMP-9 ratios might play an important role in the onset of aortic dissection, when the tunica media becomes fragile with chronic breakage and degradation of the extracellular matrix.


Calcium-dependent translocation of calbindin-D28k from intestine to blood.
Calbindin-D (vitamin D-induced calcium-binding protein; CaBP) is known to be present in blood at concentrations which vary directly with levels in the intestinal mucosa. Employing a sensitive radioimmunoassay and sampling mesentery venous blood, the present experiments demonstrated a direct relationship between intestinal calcium absorption and serum CaBP. Solutions containing 150 mM NaCl and 45Ca-labeled calcium chloride (5 or 20 mM) were placed in the lumen of ligated duodenal preparations in situ and mesentery venous blood sampled with time. The concentration of absorbed 45Ca in serum was maximal at 5 min, followed by a significant increase in mesentery CaBP maximizing at 15-20 min. Elevation of serum CaBP was not observed when calcium in the dosing solution was omitted or replaced by either glucose or glycine. The possible transfer of absorbed calcium from the enterocyte to the circulation as a CaBP complex was ruled out by calculations revealing that considerably more calcium was transferred than could be accounted for by the low and high affinity binding sites on the protein. It is proposed that vitamin D-dependent enhanced transcellular calcium transport constitutes a stimulus for the increased release of intestinal CaBP into the circulation.


Association of substance-P-immunoreactive nerves with the murine olfactory mucosa.
Location and distribution of nerve fibers immunoreactive to substance P were studied in the mouse olfactory mucosa. A moderately dense plexus of fibers is present at the interface of the olfactory epithelium and the connective tissue of the lamina propria. In addition, many immunoreactive nerve fibers are noted in close association with Bowman's glands and blood vessels in the lamina propria. However, such fibers were not observed in olfactory epithelium proper nor in the fila olfactoria. Substance-P-immunoreactivity is almost totally abolished by treatment of animals with capsaicin, an agent known to deplete substance P from primary sensory neurons. It is suggested that the substance-P-immunoreactive fibers are of sensory origin, with their perikarya most likely located in the trigeminal ganglia. Functionally, they might influence local blood flow and/or the secretion of Bowman's glands.


The effect of the molecular structure of hydroxypropyl methylcellulose on the states of water, wettability, and swelling properties of cryogels prepared with and without CaO2.
Hydroxypropyl methylcellulose (HPMC) belongs to the cellulose ether family that has hydroxyl groups substituted by hydrophobic methyl groups (DS) and hydrophilic hydroxypropyl groups (MS). Herein, the interactions between water molecules and cryogels prepared with HPMC in the presence and absence of a linear nonionic surfactant, as well as CaO2 microparticles, which react with water producing O2, were systematically investigated by sorption experiments and Time-Domain Nuclear Magnetic Resonance. Regardless of the DS and MS, most water molecules presented transverse relaxation time t2 typical of intermediate water and a small population of more tightly bound water. HPMC cryogels with the highest DS of 1.9 presented the slowest swelling rate of 0.519 ± 0.053 gwater/(g.s) and the highest contact angle values 85.250o ± 0.004o, providing the best conditions for a slow reaction between CaO2 and water. The presence of surfactant favored hydrophobic interactions that allowed the polar head of the surfactant to be exposed to the medium, resulting in a higher swelling rate and lower contact angle values. The HPMC with the highest MS presented the fastest swelling rate and the lowest contact angle. These findings are relevant for the formulations and reactions, where tuning the swelling kinetics is crucial for the final application.


A Never-Ending Journey in Search for Novel Cell Biology Techniques.
Cell techniques undergo rapid advancement across different areas of biomedical research [...].


On oscillation reduction in feedback control for processes with an uncertain dead time and internal-external disturbances.
This paper aims to find a practical solution to reduce oscillation on the Smith Predictor (SP) based design with the dead time (DT) uncertainty, making it less sensitive to DT change and more effective in disturbance rejection. First, a conditional feedback mechanism is introduced in SP to reduce the amount of oscillation caused by the model inaccuracies in the DT parameter. Then, to address the oscillation caused by the phase lag in traditional PI controller and uncertain dynamics, this conditional SP is combined with active disturbance rejection control (ADRC), assisted by the knowledge of process dynamics. A practical tuning method is provided for the practicing engineers. The proposed approach is validated in extensive simulation studies with different types of plants and in frequency domain analysis. The simulation results show significant improvements in performance robustness and transient response.


Scaphotrapezial arthritis after a carpometacarpal fusion in a patient with Marfan's Syndrome: case report.
We report a case of scaphotrapezial arthritis that developed in a patient with Marfan's syndrome many years after a carpometacarpal fusion, which placed the thumb metacarpal in adduction. This problem was effectively treated with an abduction/opposition osteotomy, which both increased the patient's first web space and improved her arthritic symptoms.


Comprehensive evaluation of candidate reference genes for gene expression studies in Lysiphlebia japonica (Hymenoptera: Aphidiidae) using RT-qPCR.
Lysiphlebia japonica (Ashmead) is a predominant parasitoid of cotton-melon aphids in the fields of northern China with a proven ability to effectively control cotton aphid populations in early summer. For accurate normalization of gene expression in L. japonica using quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR), reference genes with stable gene expression patterns are essential. However, no appropriate reference genes is L. japonica have been investigated to date. In the present study, 12 selected housekeeping genes from L. japonica were cloned. We evaluated the stability of these genes under various experimental treatments by RT-qPCR using four independent (geNorm, NormFinder, BestKeeper and Delta Ct) and one comparative (RefFinder) algorithm. We identified genes showing the most stable levels of expression: DIMT, 18S rRNA, and RPL13 during different stages; AK, RPL13, and TBP among sexes; EF1A, PPI, and RPL27 in different tissues, and EF1A, RPL13, and PPI in adults fed on different diets. Moreover, the expression profile of a target gene (odorant receptor 1, OR1) studied during the developmental stages confirms the reliability of the chosen selected reference genes. This study provides for the first time a comprehensive list of suitable reference genes for gene expression studies in L. japonica and will benefit subsequent genomics and functional genomics research on this natural enemy.


Longitudinal multiparametric MRI study of hydrogen-enriched water with minocycline combination therapy in experimental ischemic stroke in rats.
Free radicals are downstream mediators of several cytotoxic cascades contributing to ischemic brain injury. Molecular hydrogen (H2) is an antioxidant potentially useful in the treatment of stroke. Hydrogen is easy to deliver, biologically non-toxic and diffuses freely through all biological structures including the blood-brain barrier and cellular membranes. This study evaluated the efficacy of hydrogen treatments in a rat stroke model compared to vehicle-treated controls using multiparametric MRI and neurological tests. Additionally, comparison of H2 treatment alone was made with H2 combined with minocycline (H2M) treatment (12 rats per group). The primary findings were: i) H2 therapy reduced infarct volume in both H2 and H2M groups compared to controls at 1 and 7 days after stroke, and ii) both H2 and H2M improved neurologic functional recovery on day 7. The secondary outcomes were: iii) H2M treatment attenuated post-stroke hyperperfusion in the hyperacute phase, and iv) H2M markedly minimized white matter injury. In conclusion, this is the first study to use MRI to longitudinally study H2 and H2M treatment on ischemic stroke and the first study to compare H2 treatment combined with another potential stroke therapeutic (H2M).


Antigenic polymorphism of the T4 differentiation antigen expressed on human T helper/inducer lymphocytes.
The human TH lymphocyte population has been established to express a differentiation antigen (T4) which appears to function in cellular collaboration and T cell recognition of Class II MHC alloantigens. Because we observed altered immunofluorescence staining of the TH cells of some individuals using the OKT4 mAb, a systematic investigation on both the epitopic structure of the T4 glycoprotein molecule and possible polymorphism of these epitopes was undertaken. From competitive blocking assays using eight murine anti-T4 mAbs coupled with quantitative flow cytometry, at least five and possibly seven different epitopes can be recognized on the T4 molecule. Population studies showed some individuals had a reduced phenotypic expression of the OKT4 reactive determinant to one-half that of normal and others completely lacked this epitope. The OKT4 reactive epitope variations are common but have so far been racially restricted to American Blacks and do not appear related to the stage of TH cell differentiation, any identifiable immune abnormality in vitro, or a definable disease process. The OKT4 epitope cannot be unmasked by neuraminidase treatment or T cell stimulation with lectins, soluble antigens, or allogeneic lymphocytes. Coupled with a family study, the alterations in OKT4 phenotype are best explained by autosomal, codominant expression of the T4 gene product. The significance of this polymorphism on TH cell function remains unclear.


Arachnoiditis ossificans in a patient with ankylosing spondylitis, syringomyelia, and a history of spinal surgery.
In this article, we describe a patient unusual presenting with both arachnoiditis ossificans and syringomyelia. We have reviewed the patient's evaluation, surgery, and treatment. This patient developed paraparesis following thoracolumbar spinal surgery to treat kyphosis secondary to ankylosing spondylitis. We performed a T9-T11 total laminectomy, drained the cyst, dissected and removed the calcified plaques posterior to the cord, and decompressed the neural structures. Symptomatic arachnoiditis ossificans (AO) a rare clinical manifestation is characterized by the calcification or ossification of the spinal arachnoid. The occurrence of AO with syringomyelia is rare. To date, a few cases with both AO and ankylosing spondylitis have been reported.


SiHSFA2e regulated expression of SisHSP21.9 maintains chloroplast proteome integrity under high temperature stress.
High temperature-induced crop failures are prominent nowadays in major staples, including rice, wheat, and maize; however, crops such as foxtail millet (Setaria italica) are resilient to temperature stress. In this study, a novel small heat shock protein of foxtail millet, SisHSP21.9, is identified and characterized for its role in conferring tolerance to high-temperature stress. SisHSP21.9 is a panicoid-specific gene, which is highly upregulated during high-temperature in leaves, and the protein is localized in the chloroplast. Its expression is directly regulated by heat shock factor, SiHSFA2e, during temperature stress. Further, overexpression of SiHSP21.9 in rice enhanced the survival of transgenics during high-temperature stress (> 80% survival frequency), and the transgenic lines showed improved plant architecture and overall grain yield. Compared to WT plants, transgenic lines maintained optimal photosynthesis rates with higher photosystem efficiencies at high temperatures, and this is conferred through protecting the components of photosystems, chlorophyll-binding proteins, and chloroplast-localized functional proteins by SisHSP21.9. Prolonged high-temperature stress showed minimal damage to chloroplast proteins resulting in comparatively lower yield loss (35-37%) in transgenic lines. Altogether, the study suggests that SisHSP21.9 is a potential candidate for designing thermotolerant crops for climate-resilient agriculture; however, further research is needed because tolerance to abiotic stresses is polygenic.


Adolescent idiopathic scoliosis patients report increased pain at five years compared with two years after surgical treatment.
A multicenter study of changes in Scoliosis Research Society (SRS) outcome measures after surgical treatment of adolescent idiopathic scoliosis (AIS). To evaluate changes in patient determined outcome measures between 2 and 5 years after AIS surgery. Current surgical procedures have been shown to improve subjective measures in patients with AIS. At 2-year follow-up, AIS patients reported significant improvement in all 4 preoperative domains of the SRS questionnaire. In addition, the major Cobb angle was shown to be negatively correlated with preoperative scores in the pain, general self-image, and general function domains. Five-year SRS scores have not been evaluated previously. A multicenter, prospectively generated database was used to obtain perioperative, radiographic, and SRS-24 outcomes data. The inclusion criteria were: a diagnosis of AIS, surgical treatment (anterior, posterior, or combined), a comprehensive set of radiographic measures, and completed preoperative, 2-year, and 5-year SRS questionnaires. Repeated measures analysis of variance was used to compare changes in patient responses for each of the 7 outcome domains. Univariate analysis of variance was used to compare the change in pain score at 5 years to the level of the lowest instrumented vertebrae and surgical approach. A correlation analysis was used to determine the association between changes in any of the radiographic variables and changes in SRS scores. The data were checked for normality and equal variances, and the level of significance was set at P < 0.01. Forty-nine patients (42 women, 7 men; 14.2 +/- 2.1 year old; 5.4 +/- 0.6 years follow-up) met the inclusion criteria for this study. Thirty-seven of 49 (76%) of these patients underwent an open or thoracoscopic anterior procedure. SRS-24 scores improved significantly in 3 of the 4 preoperative domains at the 2-year visit. At 5 years postop, a statistically significant decrease in the pain score (4.2 +/- 0.6 to 3.9 +/- 0.9, P = 0.003) and a trend toward worsening scores in 4 other domains was observed; however, Patient Satisfaction scores remained unchanged. Lowest instrumented vertebrae and surgical approach could not be correlated to changes in the pain score. In addition, no correlation was found between changes in any of the 21 radiographic measures evaluated and changes in SRS scores. There was a statistically significant increase in reported pain from 2 to 5 years after surgical treatment; however, the etiology of worsening pain scores could not be elucidated. Given continued patient satisfaction, the clinical relevance of this small reduction remains unknown. Nevertheless, this observation deserves further evaluation and must be considered in relation to the natural history of this disease.


Editorial Commentary: Anteromedial Portal Drilling of the ACL Femoral Socket Avoids Transtibial Constraint Results in Anatomic Reconstruction and Superior Outcomes.
Femoral and tibial tunnel locations for ACL grafts should be predicated on anatomy. Regarding femoral ACL socket or tunnel creation, multiple techniques have been debated. Network meta-analysis shows that the anteromedial portal (AMP) technique results in better anteroposterior and rotational stability than does the "standard" constrained, transtibial technique based on side-to-side differences in laxity and pivot-shift tests, as well as IKDC objective scores. The AMP provides a direct shot at the anatomic ACL origin on the femur. It avoids the osseous constraint of the reamer that hampers transtibial approaches. It avoids the extra incision required by the outside-in technique and the accompanying graft obliquity. Despite the need for knee hyperflexion and the potential for shorter femoral sockets, the AMP technique should be easily reproducible for an accomplished ACL surgeon to reproduce the patient's anatomy.


[Clinical and therapeutic considerations on a case of hemangiopericytoma of the cheek].
The paper reports on a case of recurrent hemangiopericytoma of the cheek, discusses the results of hyperthermia combined with intra-arterial chemotherapy after the postoperative recurrence and draws significant conclusions about the therapeutic approach to this type of tumour.


You don't need a weatherman: famines, evolution, and intervention into aging.
Calorie restriction (CR) is the most robust available intervention into biological aging. Efforts are underway to develop pharmaceuticals that would replicate CR's anti-aging effects in humans ("CR mimetics"), on the assumption that the life- and healthspan-extending effects of CR in lower organisms will be proportionally extrapolable to humans (the "proportionality principle" (PP)). A recent argument from evolutionary theory (the "weather hypothesis" (WH)) suggests that CR (or its mimetics) will only provide 2-3 years of extended healthy lifespan in humans. The extension of healthy human lifespan that would be afforded by intervention into aging makes it crucial that resources for therapeutic development be optimally allocated; CR mimetics being the main direction being pursued for interventive biogerontology, this paper evaluates the challenge to the potential efficacy of CR mimetics posed by the WH, on a theoretical level and by reference to the available interspecies data on CR. Rodent data suggest that the anti-aging effects of CR continue to increase in inverse proportion to the degree of energy restriction imposed, well below the level that would be expected to be survivable under the conditions under which the mechanisms of CR evolved and are maintained in the wild. Moreover, the same increase in anti-aging effects continues well below the point at which it interferes with reproductive function. Both of these facts are in accordance with the predictions of evolutionary theory. Granted these facts, the interspecies data-including data available in humans-are consistent with the predictions of PP rather than those of the WH. This suggests that humans will respond to a high degree of CR (or its pharmaceutical simulation) with a proportional deceleration of aging, so that CR mimetics should be as effective in humans as CR itself is in the rodent model. Despite this fact, CR mimetics should not be the focus of biomedical gerontology, as strategies based on the direct targeting of the molecular lesions of aging are likely to lead to more rapidly developable and far more effective anti-aging biomedicines.


Energy evaluation of forest residues originated from Eucalyptus globulus Labill in Galicia.
The possibility of retrieving the energy contained in forest residues originating from wood exploitation in Galicia (Spain) is evaluated. This study was made on Eucalyptus globulus Labill occupying a forest surface of 240000 ha. This species plays an important role in the economical development of Galicia, as it is the main forest species for production of pulp. Sampling was made over 1999 in seven different zones, three main stations plus four selected for comparison, situated in Galicia. The residues originating from cutting were sorted into three different groups and their calorific values were measured by static bomb calorimetry. These calorific values, close to 7200 kJ kg(-1), make possible the use of this residual biomass as an energy source. Calorific values were measured by static bomb calorimeter in an oxygen atmosphere. Flammability was determined using a standard epiradiator. Simultaneously, some other parameters, elementary chemical composition, heavy metal contents, moisture, density, ash percentage after combustion in the bomb, and main bioclimatic characteristics, were also determined.


Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity.
We previously identified Nob1 as a quantitative trait locus for high-fat diet-induced obesity and diabetes in genome-wide scans of outcross populations of obese and lean mouse strains. Additional crossbreeding experiments indicated that Nob1 represents an obesity suppressor from the lean Swiss Jim Lambert (SJL) strain. Here we identify a SJL-specific mutation in the Tbc1d1 gene that results in a truncated protein lacking the TBC Rab-GTPase-activating protein domain. TBC1D1, which has been recently linked to human obesity, is related to the insulin signaling protein AS160 and is predominantly expressed in skeletal muscle. Knockdown of TBC1D1 in skeletal muscle cells increased fatty acid uptake and oxidation, whereas overexpression of TBC1D1 had the opposite effect. Recombinant congenic mice lacking TBC1D1 showed reduced body weight, decreased respiratory quotient, increased fatty acid oxidation and reduced glucose uptake in isolated skeletal muscle. Our data strongly suggest that mutation of Tbc1d1 suppresses high-fat diet-induced obesity by increasing lipid use in skeletal muscle.


Toxicity of plant essential oils to acaricide-susceptible and -resistant Tetranychus urticae (Acari: Tetranychidae) and Neoseiulus californicus (Acari: Phytoseiidae).
The toxicity of 10 plant essential oils to adults of acaricide-susceptible, chlorfenapyr-resistant (CRT-53), fenpropathrin-resistant (FRT-53), pyridaben-resistant (PRT-53), and abamectin-resistant (ART-53) strains of Tetranychus urticae Koch (Acari: Tetranychidae) and to female Neoseiulus californicus McGregor (Acari: Phytoseiidae) was examined using spray or vapor-phase mortality bioassays. In bioassay with the susceptible adults, lemon eucalyptus (19.3 microg/cm3) was the most toxic oil, followed by peppermint, citronella Java, thyme red, caraway seed, clove leaf, and pennyroyal oils (LC50, 20.6-23.7 microg/cm3). The toxicity of these oils was almost identical against adults from either of the susceptible and resistant strains, even though CRT-53, FRT-53, PRT-53, and ART-53 adults exhibited high levels of resistance to chlorfenapyr (resistance ratio [RR], > 9,140), fenpropathrin (RR, 94), pyridaben (RR, > 390), and abamectin (RR, 85), respectively. Against female N. californicus, lemon eucalyptus (LC50, 21.4 microg/cm3) was the most toxic oil, whereas the LC50 values of the other nine oils ranged from 23.2 to 72.6 microg/cm3. N. californicus was 1-2 times more tolerant than T. urticae to the test essential oils. Thus, these essential oils merit further study as potential acaricides for the control of acaricide-resistant T. urticae populations as fumigants.


Crusted scabies in a patient with the acquired immunodeficiency syndrome.
A case of crusted (Norwegian) scabies in a patient with the acquired immunodeficiency syndrome (AIDS) is described and seven previous reports of this association are reviewed. Injury to epidermal Langerhans' cells by the human immunodeficiency virus or cytotoxic cells may explain the appearance of this unusual form of scabies in patients with AIDS.


Interaction of amorphous calcium phosphate with fibrin in vitro causes decreased fibrinolysis and altered protease profiles: implications for atherosclerotic disease.
Previously, we demonstrated that amorphous calcium phosphate (ACP), chemical precursor to apatite, strongly interacted with fibrin and facilitated binding of matrix metalloproteinase (MMP)-9, a type IV collagenase. Plasmin-dependent fibrinolysis resulted in coordinate MMP-9 activation. Here we report on the effect(s) of ACP on fibrin degradation and binding of endogenous plasma proteases. Electrophoresis (8.5% SDS-PAGE) revealed that fibrin formed in the presence of ACP demonstrated characteristic gamma-gamma dimers (90-kDa) and beta-monomers (55-kDa), but resisted spontaneous fibrinolysis (72 h, 37 degrees C) or degradation by plasminogen activators (uPA, tPA). Casein zymography revealed an ACP-dependent decrease in fibrin binding of a low molecular weight (Mw) protease triplet (47-, 43-, 42-kDa) and increased fibrin binding of two high Mw proteases (94- and 84-kDa). The low Mw triplet also possessed gelatinolytic activity, but was not an MMP since 1,10-phenanthroline was ineffective as an inhibitor. Fibrin-binding proteases were inhibited to some degree by the serine protease inhibitor aprotinin. Competition/dissociation experiments with epsilon-aminocaproic acid revealed that the low Mw triplet lacked kringle regions whereas the 94- and 84-kDa proteases were tentatively identified and glu-/lys-plasmin(ogen)s. The triplet may, however, represent one or more kringle deficient mini-plasminogen(s), since electrophoretic mobility and substrate specificity was similar to elastase-generated mini-plasminogen. To explore these findings in a clinically relevant setting, a series of plasma samples was collected from a patient with unstable angina prior to, during, and post coronary artery bypass graft (CABG) surgery. Fibrin formed from plasma collected during and immediately post CABG was associated with increased fibrinolytic capacity and enhanced binding of a) MMP-9, b) the low Mw protease triplet (described above), and c) PA (as putative 110-kDa tPA:PAI-1 complex). The relevance of these findings to pathologic calcification of atherosclerotic plaques is discussed.


Targeting the molecular & cellular pillars of human aging with exercise.
Biological aging is the main driver of age-associated chronic diseases. In 2014, the United States National Institute of Aging (NIA) sponsored a meeting between several investigators in the field of aging biology, who identified seven biological pillars of aging and a consensus review, "Geroscience: Linking Aging to Chronic Disease," was published. The pillars of aging demonstrated the conservation of aging pathways in diverse model organisms and thus represent a useful framework with which to study human aging. In this present review, we revisit the seven pillars of aging from the perspective of exercise and discuss how regular physical exercise can modulate these pillars to stave off age-related chronic diseases and maintain functional capacity.


Differential actions of diacylglycerol acyltransferase (DGAT) 1 and 2 in regulating lipid metabolism and progesterone secretion of goose granulosa cells.
Accumulating evidence shows that granulosa cells within both mammalian and avian ovaries have the ability to synthesize fatty acids through de novo lipogenesis and to accumulate triglycerides essential for oocyte and ovarian development. However, very little is known about the exact roles of key genes involved in the lipid metabolic pathway in granulosa cells. The goal of this study was to investigate the differential actions of diacylglycerol acyltransferase (DGAT) 1 and 2, which are recognized as the rate-limiting enzymes catalyzing the last step of triglyceride biosynthesis, in regulating lipid metabolism and steroidogenesis in granulosa cells of goose follicles at different developmental stages. It was observed that the mRNAs encoding DGAT1 and DGAT2 were ubiquitous in all examined granulosa cell layers but exhibited distinct expression profiles during follicle development. Notably, the mRNA levels of DGAT1, DGAT2, FSHR, LHR, STAR, CYP11A1, and 3βHSD remained almost constant in all except for 1-2 follicles within the 8-10 mm cohort, followed by an acute increase/decrease in the F5 follicles. At the cellular level, siRNA-mediated downregulation of DGAT1 or DGAT2 did not change the amount of lipids accumulated in both undifferentiated- and differentiated granulosa cells, while overexpression of DGAT2 promoted lipid accumulation and expression of lipogenic-related genes in these cells. Meanwhile, we found that interfering DGAT2 had no effect but interfering DGAT1 or overexpressing DGAT2 stimulated progesterone secretion in undifferentiated granulosa cells; in contrast, interference or overexpression of DGAT1/2 failed to change progesterone levels in differentiated granulosa cells but differently modulated expression of steroidogenic-related genes. Therefore, it could be concluded that DGAT1 is less efficient than DGAT2 in promoting lipid accumulation in both undifferentiated- and differentiated granulosa cells and that DGAT1 negatively while DGAT2 positively regulates progesterone production in undifferentiated granulosa cells.


Optimization of a Technique to Standardize the Rodent Roux-En-Y Gastric Bypass Model and Troubleshooting of Postoperative Failures.
Rodent models are required in studies on the mechanism of Roux-en-Y gastric bypass (RYGB). However, the construction of the model is hard, and there are various causes of death after surgery in rats. RYGB models with procedures containing a series of anatomic landmark were established in rats. Optimized procedures during surgery, possible complications after surgery, and corresponding solutions were studied. With the introduction of perioperative nursing and optimized surgery procedures, less time-consuming surgeries were performed and higher survival rates were achieved. Trouble-shooting data based on death time points are listed and discussed for various causes of failure. This study provides practical suggestions for investigators to perform RYGB surgery on rats. The troubleshooting suggestions will help operators to efficiently identify problems in their procedures.


Chemodenervation of strabismic children. A 2- to 5-year follow-up study compared with shorter follow-up.
To determine longer-term efficacy of botulinum treatment, the author examined 85 children younger than 14 years of age who had been treated from November 1982 to February 1984, comparing shorter follow-up (range, 6-24 months) with longer follow-up (range, 2-5.5 years) as of last examination before March 1988. Fifty esotropes meeting the 2-year criteria for follow-up had an average of 35 prism diopters (PD) before and 5 PD after treatment. Twelve exotropes averaged 30 and 5 PD. No long-term complications were discovered. The results are similar to the shorter follow-up and suggest that botulinum is effective in creating a 2- to 5-year stable improvement for strabismic children.


[Peutz-Jeghers syndrome: report of 4 cases].
Four patients with Peutz-Jeghers syndrome were consecutively observed according to their clinical manifestation, pathologic characteristic, family history. Four cases were analyzed according to their clinical observation, X-ray detection, pathological diagnosis and family history. Peutz-Jeghers syndrome had characteristic of family inhereditary. Intestinal lesion was correlative to canceration of polypus. Family inhereditary detection should be performed in Peutz-Jeghers syndrome patients. The patients whose intestinal lesion was located in colon were considered high risk patients. They should be intensively cared regularly in long-term.


Risk stratification assessed by combined lung and heart iodine-123 metaiodobenzylguanidine uptake in patients with idiopathic dilated cardiomyopathy.
Iodine-123 metaiodobenzylguanidine (123I-MIBG) has been used to assess myocardial sympathetic nervous activity and severity of heart failure. (123)I-MIBG is also used as a potential marker of pulmonary endothelial cell function and may be related to pulmonary hypertension. Thus, we hypothesized that combined assessment of lung and heart 123I-MIBG kinetics predicts future clinical outcome more accurately than myocardial evaluation alone in patients with chronic heart failure. To test this hypothesis, we examined 123I-MIBG scintigrams in 62 consecutive patients with idiopathic dilated cardiomyopathy. Anterior planar images were obtained 15 minutes and 3 hours after 123I-MIBG injection. Cardiac and pulmonary 123I-MIBG activities were quantified as heart-to-mediastinum activity ratio and lung-to-mediastinum activity ratio. We introduced lung-to-heart activity ratio as the new 123I-MIBG parameter including myocardial sympathetic nerve activity and pulmonary endothelial cell function. Delayed lung-to-heart ratio was correlated with pulmonary vascular resistance (r = 0.48, p <0.0001), disease duration (r = 0.49, p <0.0001), and number of heart failure episodes (r = 0.55, p <0.0001). During a mean follow-up of 25 months, 15 patients had a cardiac event. Area under receiver operating characteristic curves for prediction of the event was greatest in delayed lung-to-heart ratio (lung to heart 0.92, heart to mediastinum 0.83, lung to mediastinum 0.80). In multivariate analysis, the lung-to-heart ratio (hazard ratio 2.76/0.1 increase, p = 0.002) was selected as an independent predictor for a future cardiac event. In conclusion, the combined assessment of lung and heart 123I-MIBG uptake may help to predict future clinical outcome for patients with idiopathic dilated cardiomyopathy more accurately than myocardial evaluation alone.


A dual-mode nanoprobe for the determination of parathion methyl based on graphene quantum dots modified silver nanoparticles.
We developed a highly sensitive and selective method for double-signal analysis (fluorescence and ultraviolet-visible spectrophotometry) of organophosphorus pesticides (OPs), based on reversible quenching of graphene quantum dots (GQDs; fluorophores) with silver nanoparticles (AgNPs; absorbers). We used acetylcholinesterase to catalytically convert acetylthiocholine into thiocholine. In turn, by competitive binding to the AgNPs, the produced thiocholine displaces AgNPs from the GQDs and thus induces fluorescence recovery. However, OP analytes inhibit the activity of acetylcholinesterase and, in so doing, retain the silver-graphene nanoparticle complex and fluorescence quenching. The degree of quenching is proportional to the concentration of OPs; the detection limit is as low as 0.017 μg/L. The ultraviolet-visible absorption of GQDs/AgNPs at 390 nm decreases-because of AgNP aggregation that occurs after desorption from the GQDs-and the absorbance is linearly proportional to the OP concentration. Our system has good selectivity to substances that are commonly present in water and vegetables. We successfully applied our method to OP analysis in water, apple, and carrot samples.


Studies on the mechanism of the cardiotonic activity of MDL 19205: effects on several biochemical systems.
MDL 19205, 4-ethyl-1,3-dihydro-5-(4-pyridinyl-carbonyl)-2H-imidazol-2-one, is a new drug with cardiotonic properties. Its effects on several biochemical systems considered to be important in myocardial contraction were investigated. Cyclic nucleotide phosphodiesterases (PDEs) from dog hearts were separated into three isoenzymes, F I, F II, and F III, and effect of the drug on these enzymes was tested. MDL 19205 inhibited F III PDE specifically and produced little or no inhibition of F I and F II PDEs. The IC50 for inhibition of F III PDE was 8.6 microM when 0.5 microM cyclic AMP (cAMP) was used, whereas no more than 10% inhibition of F I and 18% of F II PDEs occurred at drug concentrations up to 200 microM when 1 microM cAMP was used. Concentrations of MDL 19205 up to 100 microM had no effect on Ca2+-adenosine triphosphatase (ATPase) or Ca2+ uptake by dog cardiac sarcoplasmic reticulum. At 100 microM, the drug produced a weak (18%) inhibition of Na+,K+-ATPase. It is suggested that inhibition of F III PDE may be the primary mechanism by which MDL 19205 produces its cardiotonic effect. Inhibition of Na+,K+-ATPase may also be involved at very high concentrations of this drug.


Heterogeneity of chlorinated hydrocarbon sorption properties in a sandy aquifer.
Hydraulic conductivity and sorption coefficients for chlorinated hydrocarbons (chloroform, carbon tetrachloride and tetrachloroethylene) were evaluated for 216 sediment samples collected across a 15 m transect and a 21 m depth interval in a contaminated aquifer near Schoolcraft, Michigan. Relationships between hydraulic conductivity, linear sorption partition coefficients, grain size classes, and spatial location were investigated using linear regression analysis and geostatistical techniques. Clear evidence of layering was found in sorption properties, hydraulic conductivity and grain sizes. Conductivity correlated well with grain size, as expected, but sorption varied inversely with grain size, contrary to some previous reports. No significant correlation was found between sorption properties and hydraulic conductivity. This is likely due to the unexpected presence of small amounts of highly sorptive coal-like solids, which dominate the sorption behavior but have little effect on conductivity. The results demonstrate that recent findings regarding the high sorption capacity of coal materials found in soils can exert a controlling influence on contaminant transport. Designers of in situ remediation systems should be cautioned that 1) it is not reasonable to assume that sorption capacity and hydraulic conductivity are related, 2) sorption capacity and hydraulic conductivity are critical measurements for contaminant site characterization and subsequent transport modeling, 3) estimating sorption capacity from organic carbon measurement may lead to greater errors than performing sorption isotherms, and 4) it is more important to characterize vertical heterogeneity rather than horizontal heterogeneity because both sorption and hydraulic conductivity are correlated across longer distances in the horizontal plane.


Nonlinear dynamical structure of sway path during standing in patients with multiple sclerosis and in healthy controls is affected by changes in sensory input and cognitive load.
Although several studies have applied traditional linear measures to evaluate postural control of patients with multiple sclerosis (MS), little is known about the nonlinear dynamics of this patient group. In this study, recurrence quantification analysis (RQA), a well documented nonlinear method, was used to compare the nonlinear dynamical structure of postural sway in two groups consisting of MS patients (n=23) and healthy matched controls (n=23). The study focuses on three levels of postural difficulty consisting of (1) standing on a rigid surface (force platform) with eyes open, (2) standing on a rigid surface with eyes closed, and (3) standing on a foam surface with eyes closed. The two levels of cognitive difficulty measured, consisted of a single postural task and a dual postural-cognitive task. It was observed that as the postural conditions became more difficult, the center of pressure (COP) time series of both groups became less regular as recorded in lower recurrence rate, less complex in deterministic structure as reflected in lower RQA entropy, and less nonstationary as reflected in the recording of lower Trend. Moreover, as cognitive conditions became more difficult, COP time series became less regular (lower %Rec in the anteroposterior direction and lower %Det in both directions), less complex in deterministic structure (lower RQA Ent in the anteroposterior direction), and less nonstationary (lower trend in the anteroposterior direction). The analytical results of the research show that there is a similar dynamical structure for both the MS patients and the control group; however, the nonlinear behavior of both groups was different under various experimental conditions.


[Radiological study of the hand of patients undergoing periodic hemodialysis. Possibilities and limitations of the method as an index of the evolution of the uremic disease].
The periodic X-ray examination of the hand in 50 patients in hemodialysis shows a good correlation between the radiologic findings and bone bioptic patterns. The method had instead a lesser interest in following the evolution of vascular and metastatic calcification.