Multiobjective optimization of a hybrid electricity generation system based on waste energy of internal combustion engine and solar system for sustainable environment.
In recent years, the interest in generating power through hybrid power generation systems has increased. In this study, a hybrid power generation system including an internal combustion engine (ICE) and a solar system based on flat plate collectors to generate electricity is investigated. To benefit from the thermal energy absorbed by solar collectors, an organic Rankine cycle (ORC) is considered. In addition to the solar energy absorbed by the collectors, the heat source of the ORC is the wasted heat through exhaust gases and the cooling system of the ICE. A two-pressure configuration for ORC is proposed for optimal heat absorption from the three available heat sources. The proposed system is installed to produce power with a capacity of 10 kW. A bi-objective function optimization process is carried out to design this system. The objective of the optimization process is to minimize the total cost rate and maximize the exergy efficiency of the system. The design variables of the present problem include the ICE rated power, the number of solar flat plate collectors (SFPC), the pressure of the high-pressure (HP) and low-pressure (LP) stage of the ORC, the degree of superheating of the HP and LP stage of the ORC, and its condenser pressure. Finally, it is observed among the design variables the most impact on total cost and exergy efficiency is related to the ICE rated power and the number of SFPCs.


Developmental and methylmercury effects on brain protein synthesis.
Sprague-Dawley rats (ages 1 to 21 days, alternate days) were chosen for study. Animals were injected with methylmercuric chloride (8 mg/kg IP); 12 hr later each animal was injected with uniformly labeled L-(14C)leucine, allowed 30 min for incorporation, and decapitated. Brains were analyzed for amounts of radioactivity incorporated into TCA precipitable protein. When compared to baseline curves for control animals, curves of treated animals were compressed overall and had age-dependent increases and decreases in rates of protein synthesis.


Complexes between ovalbumin nanoparticles and linoleic acid: Stoichiometric, kinetic and thermodynamic aspects.
Stoichiometric, kinetic and thermodynamic aspects of complex formation between heat-induced aggregates of ovalbumin (ovalbumin nanoparticles, OVAn) and linoleic acid (LA) were evaluated. Extrinsic fluorescence data were fitted to modified Scatchard model yielding the following results: n: 49±2 LA molecules bound per OVA monomer unit and Ka: 9.80±2.53×10(5)M. Kinetic and thermodynamic properties were analyzed by turbidity measurements at different LA/OVA monomer molar ratios (21.5-172) and temperatures (20-40°C). An adsorption approach was used and a pseudo-second-order kinetics was found for LA-OVAn complex formation. This adsorption process took place within 1h. Thermodynamic parameters indicated that LA adsorption on OVAn was a spontaneous, endothermic and entropically-driven process, highlighting the hydrophobic nature of the LA and OVAn interaction. Finally, Atomic Force Microscopy imaging revealed that both OVAn and LA-OVAn complexes have a roughly rounded form with size lower than 100nm.


Immunophenotyping of blood mononuclear cells from P. berghei (NK-65) infected and immunized BALB/c mice.
The present study demonstrates the alterations in the frequencies of helper, cytotoxic and suppressor T cells in blood of P. berghei infected and TPA immunized rodent host towards the induction of protective immune response. Statistically significant (p < 0.005) number of CD4+ T cells was recorded on D9 [Post Challenge (PC)] meanwhile CD4+ Treg cells were found to be declined in immunized mice as compared to infected. This increase in frequencies of T helper cells points towards the stimulation of strong Th2 immune response in immunized mice. Statistically significant (p < 0.005) decline was observed in the frequencies of CD8+ T cells on D9 (PC) in immunized mice. In infected controls cytotoxic T cells were also found to be increased after 24 h post infection. Due to strong Th2 immune response, evident from lower frequencies of CD4+ Treg cells in immunized mice, complete protection was obtained. T reg population was found to be higher in infected controls and all control mice died.


Cortactin contributes to the tumorigenesis of gastric cancer by activating ERK/MMP pathway.
Gastric cancer is a malignant tumor with high mortality and high incidence. This study aims to explore the function and molecular mechanism of Cortactin on gastric cancer progression in vitro and in vivo. A bioinformatics analysis from TCGA displayed that Cortactin was highly expressed in gastric cancer samples, and patients with a high Cortactin level had a worse survival rate. Subsequently, we investigated the specific mechanism of action of A in gastric cancer by collecting patient samples for immunohistochemistry, WB, qRT-PCR, cell transfection, cell invasion and metastasis, and constructing tumor xenografts in nude mice. Overexpression of Cortactin inhibited apoptosis and enhanced cellular proliferation and mobility in AGS cells, while those activities were reversed by the knockdown of MMP2 or MMP9. Conversely, the deletion of Cortactin induced apoptosis and suppressed cell growth and metastasis in SGC7901 cells, whereas those behaviors were inhibited by overexpression of MMP2 or MMP9. Additionally, the ERK pathway was activated by Cortactin upregulation. In vivo studies presented that overexpression of Cortactin promoted tumor growth, increased Ki67 expression, and reduced caspase 3 expression, which was reversed by ERK inhibitor treatment. In conclusion, Cortactin acted as an oncogene in gastric cancer and exerted its function by ERK/MMP2/MMP9 signaling pathway.


Purification and characterization of a high molecular weight ribonuclease from human milk.
We have purified a high molecular weight ribonuclease (hmRNase) from human milk by a two-step column chromatographic procedure and characterized the enzyme. The molecular mass of hmRNase is 80 kDa as determined from SDS-polyacrylamide gel electrophoresis. The pH optimum of the enzyme is in the range of 7.5-8.0, similar to other secretory RNases. hmRNase is pyrimidine-specific and cleaves the phosphodiester bond 3' to a pyrimidine residue. It selectively degrades the pyrimidine strand in poly(rA):poly(rU) and poly(dA):poly(rU) double stranded substrates. The extent of degradation for naturally occurring RNAs vary in the order tRNA < rRNA < mRNA at low enzyme concentrations. hmRNase shows allosteric behavior with positive cooperativity in its reaction on polynucleotide substrates. The activity of the enzyme is enhanced in the presence of monoribonucleotides. Antiserum obtained against purified hmRNase did not cross-react with low molecular weight RNase which is also present in milk. In addition, an immunologically cross-reacting species could not be detected in the serum, suggesting the origin of hmRNase in the mammary gland but not blood.


The functional cell surface glycoprotein CD9 is distinguished by being the major fatty acid acylated and a major iodinated cell-surface component of the human platelet.
We showed that a 22 kDa protein (which comigrated with the leukocyte differentiation antigen CD9 as determined by immunoblotting with the platelet-activating mAb 50H.19) is a major iodinated component of the platelet surface. The iodinated protein was identified as CD9 by limited proteolysis analysis. The major acylated protein in platelets incubated with [3H]palmitic acid also had a mobility of 22 kDa. The radiolabelled fatty acid in CD9 appears to be ester bonded, as it is removed by treatment with hydroxylamine. Non-enzymatic ligation of the fatty acid is not involved. Since platelets lack protein synthetic capacity, the palmitolation of a surface protein indicates the existence of a plasma-membrane located transacylase which functions independently of protein synthesis. Limited proteolysis analysis of the palmitylated protein obtained by immunoprecipitation with mAb 50H.19 confirmed its identity as CD9. An additional novel minor component of 27 kDa was detected in platelets by immunoprecipitation of 125I-surface-labelled, or [3H]palmitic acid-labelled protein, and by immunoblotting with mAb 50H.19. The analogous cleavage patterns obtained by the limited proteolysis analysis of the 22, 24 and 27 kDa glycoproteins suggest that they may be differently modified variants of a single polypeptide.


On the prevention and treatment of calcification disorders of old age.
From several investigations it is known that magnesium oxide or hydroxide therapy causes a considerable delay of kidney stone recurrence in man. Further, it is known that the mortality of populations due to cardiovascular disease in areas with hard drinking water containing more magnesium and having a higher Mg/Ca ratio than soft water, is considerably lower than in soft water areas. In the present study a physiological model for the homeostasis of calcium and phosphate is given. It is shown that and why a slight magnesium deficiency causes the pH of bone extracellular fluid to decrease at or below the pH level of the other body fluids. This decrease makes the other body fluids supersaturated with octocalcium phosphate and this is the prime reason for calcification disorders in the soft tissues. Therefore, the hypothesis is proposed that soft tissue calcifications can be stopped and even prevented by magnesium therapy. However, they are not reversible and treatment with chelate therapy is contraindicated.


Rotaglide-facilitated stent delivery: mission accomplished.
Percutaneous coronary interventions are performed with a high success rate, though failures still occur. Inability to deliver stents to the target lesion is the most common cause for failures. We present two cases using Rotaglide applied on the stents to enable delivery, showing that Rotaglide is effective in improving stent delivery.


The influence of seasonal variation on cardiac surgery: a time-related clinical outcome predictor.
The effect of seasonal variation on cardiac surgery outcomes is unknown. We investigated the effect of season on risk-adjusted hospital mortality and length of stay. Prospectively collected data from cardiac operations at one center between April 1996 and March 2006 were analyzed. Seasonal variation in outcomes was studied by using multiple regression models that included EuroSCORE and year of operation to adjust for risk profile and changes over time. Analysis was performed for 2 separate surgical groups: patients having coronary artery bypass grafting only and patients having other cardiac procedures with or without coronary artery bypass grafting. There were 16,290 patients who had a first record of cardiac surgery in the study period between April 1, 1996, and March 31, 2006, with 10,263 patients having coronary artery bypass grafting only and 6027 patients having another procedure with or without coronary artery bypass grafting. There were increased odds of hospital mortality in patients having operations in winter compared with the average across all seasons for both surgical groups, although this was only significant in the coronary artery bypass grafting-only group (odds ratio, 1.29; 95% confidence interval, 1.01-1.63; P = .04). There were decreased odds of death in the coronary artery bypass grafting-only group in summer (odds ratio, 0.76; 95% confidence interval, 0.60-0.96; P = .02). Intensive care unit stay was 4% (95% confidence interval, 1%-6%) longer in the coronary artery bypass grafting-only group in winter and 3% (95% confidence interval, 1%-5%) shorter in summer than the average stay (P = .003 and .006, respectively). There were no differences in intensive care unit stay in the combined surgery group by season and no differences in total length of stay for either group (coronary artery bypass grafting only and coronary artery bypass grafting with other cardiac procedures). Cardiac surgery outcomes are influenced by the time of year. Hospital mortality and intensive care unit stay after coronary artery bypass grafting were increased during the winter season compared with the rest of the year.


Treatment of Rapid Progression of Myopia: Case Series and Literature Review.
This retrospective case series demonstrates the combination of 0.05% atropine with MiSight® 1 day (Cooper vision, Sar Ramon, CA, USA) in rapid progression of myopia of 4 children. MiSight® 1 day is a peripheral defocus, center-distance soft contact lens and is effective at controlling moderate progression of myopia during the course of 1 year. The current case series included 2 females and 2 males with an average age of 9.68 ± 0.26 years and an average axial length of 24.81 ± 0.92 mm. Their myopic progression during the previous year was -1.45 ± 0.27 D. The children had not attempted any myopia control thus far. This relatively high increase prompted a combination treatment of daily instillation of 0.05% atropine and MiSight, a daily replacement soft contact lens. Cycloplegic refraction and a slit-lamp evaluation were performed every 6 months to confirm no adverse reactions or staining was present. The 8-item contact lens dry eye questionnaire (CLDEQ-8) score of these children was 10.66 ± 1.52. The average myopia progression at the end of 1 year decreased to -0.41 ± 0.11 D, and the average axial length increase was 0.28 ± 0.08 mm. To the best of the authors' knowledge, this is the first published study showing a combination of 0.05% atropine and peripheral defocus soft contact lenses indicating efficacy at controlling moderate myopia progression.


Inhibitory effect of progesterone during early embryonic development: Suppression of myocardial differentiation and calcium-related transcriptome by progesterone in mESCs: Progesterone disturb cardiac differentiation of mESCs through lower cytosolic Ca(2.).
Progesterone (PG) and its derivates are used in prevention of spontaneous miscarriage. However, some studies have reported that exposure to PG and its derivates during pregnancy can cause malformations and affect both blood pressure and the cardiovascular system. The effect of PG on cardiomyogenesis of mouse embryonic stem cells (mESCs) is not well known. Expression of Pgr mRNA showed an opposite pattern of beating-ratio during differentiation. PG treatment resulted in reduction of the beating ratio to 60.45±1.54% from 92.17±2.98% in normal differentiation, reduced transcripts of heart morphogenesis and Ca(2+) binding-related genes in the next generation sequencing data and significantly decreased expression levels of Ca(2+)/contraction-related genes including Ryr2, Calm2, Trpv2, and Mylk3, the intracellular Ca(2+) level, and the beating frequency. These results suggest that PG exerts inhibitory effects on differentiation of mESCs into functional cardiomyocytes.


[Minimally invasive arthroscopic-assisted arthrodesis of the first metatarsophalangeal joint].
Clinical and radiographic analysis of a minimally invasive arthrodesis technique of the first metatarsophalangeal joint. Symptomatic hallux rigidus, symptomatic hallux rigido-valgus, hallux varus. Absolute contraindication (CI): osteomyelitis; relative CI: untreated diabetes mellitus, smoking. Under arthroscopic assistance, a minimally invasive arthrodesis technique of the first metatarsophalangeal joint is performed with removal of the subchondral sclerosis and remaining cartilage of the osteoarthritic joint. Immediate weight-bearing starts on day 1 using a ready-made hallux valgus shoe for 6 weeks. Physiotherapy without movement of the first metatarsophalangeal joint is allowed after surgery. A series of 5 patients with symptomatic hallux rigidus and relevant medical diseases were evaluated after minimally invasive arthroscopic arthrodesis of the first metatarsophalangeal joint. In all cases osseous union was found after 8.4 months. Follow-up was 22.6 months and the American Orthopedic Foot and Ankle Society (AOFAS) score increased significantly from 42.4 to 82.8 points. No complications requiring therapy were observed in our cohort nor was revision surgery necessary. The results of our series are in line with the published results of minimally invasive fusion techniques of the first metatarsophalangeal joint.


Association between social and family support and antenatal depression: a hospital-based study in Chengdu, China.
Antenatal depression (AD) is considered as one of the major health burdens and has adverse effects on the outcome of expectant mothers and newborns. The present study aims to investigate the prevalence of antenatal depression (AD), and to explore the potential risk factors of AD among pregnant women in Chengdu, including personal background, related social factors, family factors and cognitive factors. The prospective nested case-control study included pregnant women who were in their second pregnancy and attended prenatal care at three tertiary hospitals and one regional hospital in Chengdu, China, between March 2015 and May 2016. Self-designed questionnaires were given to participants in their second and third trimesters to collect information on clinical and demographic characteristics, and a modified edition of Edinburgh Postnatal Depression Scale (EPDS) were used to measure AD. The logistic regression was applicated in analyses. A total of 996 pregnant women were included in analysis. Ninety-three women suffered from AD symptoms only in their second trimester, 96 only in their third trimester, and 107 displayed persistent depression in both trimesters. In the univariate analyses, age and marital relationships were linked with AD occurrence in both second and third trimester. In addition, increasing age, full-time job, higher education level, and no gender preference of spouse were associated with reduced persistent depression. Multivariate analysis showed that gender preference and marital relationship were the potential risk factors of persistent depression. Age, marital relationship relationships, with parents-in-law, the negative recognition of this pregnancy and husband's gender preference were found as risk factors of AD occurrence in some specific trimester. Gender preference of husbands and marital relationships were independently associated with persistent depression. These findings suggest that stronger family support can help improve mental health of pregnant women.


Surplus Carbon Drives Allocation and Plant-Soil Interactions.
Plant growth is usually constrained by the availability of nutrients, water, or temperature, rather than photosynthetic carbon (C) fixation. Under these conditions leaf growth is curtailed more than C fixation, and the surplus photosynthates are exported from the leaf. In plants limited by nitrogen (N) or phosphorus (P), photosynthates are converted into sugars and secondary metabolites. Some surplus C is translocated to roots and released as root exudates or transferred to root-associated microorganisms. Surplus C is also produced under low moisture availability, low temperature, and high atmospheric CO2 concentrations, with similar below-ground effects. Many interactions among above- and below-ground ecosystem components can be parsimoniously explained by the production, distribution, and release of surplus C under conditions that limit plant growth.


Articular pharmacokinetics of protein-bound antirheumatic agents.
By what mechanism do nonsteroidal anti-inflammatory drugs (NSAIDs) move from plasma into synovial fluid and back, and how does binding to plasma albumin in vitro relate to articular transport in vivo? To evaluate these issues, concurrent plasma and synovial fluid data of 8 different NSAIDs from 10 single-dose trials were analysed by a simple compartmental model incorporating intra-articular volume, synovial plasma flow rates and protein transport. All pharmacological and physiological data were taken from published studies of chronic knee effusions in patients with rheumatoid arthritis. The analysis shows that these protein-bound NSAIDs readily leave the vasculature and enter synovial fluid during each transit of synovial microvessels. The mean rate of transport, 0.23 min-1, is consistent with passive diffusion at rates far in excess of those attributable to movement of albumin-bound drug or of the small, free-drug fraction found by equilibrium dialysis. These findings are explained by association and dissociation of NSAIDs and albumin that occur far more rapidly than vascular transit. Ongoing dissociation makes bound drug available for transvascular exchange and thereby diminishes the pharmacokinetic significance of binding data obtained in vitro.


Leukocyte reduction during orthotopic liver transplantation and postoperative outcome: a pilot study.
To investigate the effect of intraoperative leukocyte reduction of administered blood products on the incidence of acute cellular rejection and postoperative patient outcome. Prospective, nonrandomized, historical control study. Academic tertiary medical center. The study group (Group 1) consisted of 30 consecutive adult patients with end-stage liver disease scheduled to undergo orthotopic liver transplantation (OLT) between 1998 and 2000. The historical control group (Group 2) consisted of 30 adult patients with end-stage liver disease matched to study group patients as closely as possible for age, gender, and etiology of liver disease who underwent OLT between 1995 and 1999. Group 1 patients had all intraoperative allogeneic and cell salvaged blood products leukocyte reduced before administration. Group 2 patients underwent OLT without leukocyte filtration of any administered blood products. Demographic data were collected for both patient groups and included age, gender, etiology of liver disease, and both intraoperative and postoperative immunosuppression. Demographic allograft donor data for both patient groups were collected and included age, gender, use of vasopressors during procurement, and cold and warm donor organ ischemic times. Outcome variables measured included incidence of acute cellular rejection, length of intensive care unit (ICU) and length of hospital stay, incidence of both graft loss and retransplantation, and mortality. The incidence of acute cellular rejection was 40% in Group 1 and 66.7% in Group 2 (p = 0.037). Length of ICU stay was 3.0 (2.0, 5.0) days in Group 1 and 4.0 (3.0, 6.0) days in Group 2 (p = 0.16). Length of hospital stay was 14.0 (11.0, 18.0) days in Group 1 and 18.0 (14.0, 27.0) days in Group 2 (p = 0.035). One allograft was lost in Group 2 because of primary nonfunction requiring retransplantation (p = 0.31), and three postoperative deaths occurred in Group 1 as a result of multisystem organ failure (p = 0.08). Coincident with leukocyte reduction of all administered blood products during OLT, an improved outcome was observed in Group 1 patients as demonstrated by both a decreased incidence of acute cellular rejection and length of hospital stay.


HIV-1 tracing method of systemic viremia in vivo using an artificially mutated virus pool.
The appearance of human immunodeficiency virus type 1 (HIV-1) plasma viremia is associated with progression to symptomatic disease and CD4+ T cell depletion. To locate the source of systemic viremia, this study employed a novel method to trace HIV-1 infection in vivo. We created JRCSFξnef, a pool of infectious HIV-1 (strain JR-CSF) with highly mutated nef gene regions by random mutagenesis PCR and infected this mutated virus pool into both Jurkat-CCR5 cells and hematopoietic stem cell-transplanted humanized mice. Infection resulted in systemic plasma viremia in humanized mice and viral RNA sequencing helped us to identify multiple lymphoid organs such as spleen, lymph nodes, and bone marrow but not peripheral blood cells as the source of systemic viremia. Our data suggest that this method could be useful for the tracing of viral trafficking in vivo.


[The outcomes of coronary artery bypass and aortic valve replacement in elderly patients].
To study the outcome of open heart surgery in an increasing population of elderly patients in Iceland. A retrospective study of patients (n=876) that underwent coronary artery bypass (CABG) or aortic valve replacement (AVR) for aortic stenosis in Iceland 2002-2006. Complication rates, operative mortality and long-term survival were compared between patients older (n=221, 25%) and younger (n=655, 75%) than 75 years. Long-term survival of the older group was compared to an age and sex matched reference population. Older patients had a higher incidence of atrial fibrillation (57% vs. 37%, p<0.001), stroke (5% vs. 1%, p=0.009) and operative mortality (9% vs. 2%, p<0.001) following CABG. Length of ICU stay was similar but total length of stay was one day longer in the older cohort. Following AVR, older patients had a higher incidence of atrial fibrillation (90% vs. 71%, p=0.006), ARDS (19% vs. 7%, p=0.04), myocardial infarction (21% vs. 8%, p=0.05) and operative mortality (11% vs. 2%, p=0.04). The ICU stay was a day longer and the total length of stay was about four days longer in the older cohort. A total of 75% of the older patients were alive five years after CABG, compared to 74% of the reference population (p=0.87). Similar numbers for AVR were 65% for the patients compared to 74% in the reference population (p=0.06). The rate of complications, operative mortality and length of hospital stay is higher in patients older than 75 years compared to younger patients. Survival of the older group of patients indicates good long-term results after open heart surgery for this patient cohort.


The DedA superfamily member PetA is required for the transbilayer distribution of phosphatidylethanolamine in bacterial membranes.
The sorting of phospholipids between the inner and outer leaflets of the membrane bilayer is a fundamental problem in all organisms. Despite years of investigation, most of the enzymes that catalyze phospholipid reorientation in bacteria remain unknown. Studies from almost half a century ago in Bacillus subtilis and Bacillus megaterium revealed that newly synthesized phosphatidylethanolamine (PE) is rapidly translocated to the outer leaflet of the bilayer [Rothman & Kennedy, Proc. Natl. Acad. Sci. U.S.A. 74, 1821-1825 (1977)] but the identity of the putative PE flippase has eluded discovery. Recently, members of the DedA superfamily have been implicated in flipping the bacterial lipid carrier undecaprenyl phosphate and in scrambling eukaryotic phospholipids in vitro. Here, using the antimicrobial peptide duramycin that targets outward-facing PE, we show that Bacillus subtilis cells lacking the DedA paralog PetA (formerly YbfM) have increased resistance to duramycin. Sensitivity to duramycin is restored by expression of B. subtilis PetA or homologs from other bacteria. Analysis of duramycin-mediated killing upon induction of PE synthesis indicates that PetA is required for efficient PE transport. Finally, using fluorescently labeled duramycin we demonstrate that cells lacking PetA have reduced PE in their outer leaflet compared to wildtype. We conclude that PetA is the long-sought PE transporter. These data combined with bioinformatic analysis of other DedA paralogs argue that the primary role of DedA superfamily members is transporting distinct lipids across the membrane bilayer.


Spontaneous bilateral patellar tendon rupture: a case report and review of the literature.
Bilateral rupture of the patellar tendon is a very rare injury. It occurs in association with chronic systemic diseases or corticosteroid medications. We report a case of a 13-year-old child with Ehlers-Danlos syndrome presenting a bilateral patellar tendon disruption of proximal insertion that occurred with a trivial trauma. Surgical management consisting in tendon repair with a suture anchor technique protected temporarily with a cerclage wiring gives a good outcome.


Heterogeneity of gestational diabetes (GDM) and challenges in developing a GDM risk score.
Gestational diabetes (GDM) affects a growing number of women and identification of individuals at risk, e.g., with risk prediction models, would be important. However, the performance of GDM risk scores has not been optimal. Here, we assess the impact of GDM heterogeneity on the performance of two top-rated GDM risk scores. This is a substudy of the RADIEL trial-a lifestyle intervention study including women at high GDM risk. We assessed the GDM risk score by Teede and that developed by Van Leeuwen in our high-risk cohort of 510 women. To investigate the heterogeneity of GDM, we further divided the women according to GDM history, BMI, and parity. With the goal of identifying novel predictors of GDM, we further analyzed 319 women with normal glucose tolerance in the first trimester. Both risk scores underestimated GDM incidence in our high-risk cohort. Among women with a BMI ≥ 30 kg/m2 and/or previous GDM, 49.4% developed GDM and 37.4% received the diagnosis already in the first trimester. Van Leeuwen score estimated a 19% probability of GDM and Teede succeeded in risk identification in 61%. The lowest performance of the risk scores was seen among the non-obese women. Fasting plasma glucose, HbA1c, and family history of diabetes were predictors of GDM in the total study population. Analysis of subgroups did not provide any further information. Our findings suggest that the marked heterogeneity of GDM challenges the development of risk scores for detection of GDM.


A Comparison of Three Rubber Dam Systems In Vivo--A Preliminary Study.
The aim of this study was to compare the isolation systems OptraDam® Plus and OptiDam™ with the conventional rubber dam in terms of objective and subjective parameters. The isolation systems were applied during the dental treatment of the patients. The time of preparation, placement, presence and removal were measured and the quality of isolation was evaluated. The median time of rubber dam placement was 76 s (Q1=62 s; Q3=111.25 s). The application time of OptraDam® Plus was significantly longer compared to the other systems (P ® plus. The results presented in this study could guide clinicians for choosing the most appropriate isolation system.


Full configuration interaction calculations of the second hyperpolarizabilities of the H4 model compound: summation-over-states analysis and interplay with diradical characters.
The second hyperpolarizability (γ) of the one-dimensional H(4) model compound has been calculated at the full configuration interaction level to describe its relationships with the diradical characters y(i) [the occupation numbers of the lowest unoccupied natural orbital (LUNO) + i] and the geometry. It is found that the system with intermediate y(0) ( = 0.527) and small y(1) ( = 0.178) exhibits the largest γ value [enhanced by a factor of 9 compared to that of a nearly closed-shell H(4) analog (y(0) = 0.099, y(1) = 0.029)], where both the outer H-H distances are slightly larger than the inner one. These results provide a molecular design guideline for enhancing and controlling the third-order nonlinear optical properties of singlet multiradical linear molecular systems such as multiradical organic aggregates, supermolecular systems, and extended metal atom chains.


A Technique Using a Low-Cost, Accessible Cannula to Aid Scaffold Passage in Dry Arthroscopic Cartilage Repair in the Knee.
Although autologous matrix-induced chondrogenesis has grown increasingly popular, it can be technically challenging to place the scaffold within the knee efficiently without extending the arthroscopic incisions. To facilitate arthroscopic placement of the matrix into the knee, we developed a technique that involves fashioning a cannula from a standard 5-mL syringe. This technique enables surgeons to conveniently and efficiently place the matrix through the standard arthroscopic ports at minimal cost.


Activity-dependent potentiation of calcium signals in spinal sensory networks in inflammatory pain states.
The second messenger calcium is a key mediator of activity-dependent neural plasticity. How persistent nociceptive activity alters calcium influx and release in the spinal cord is not well-understood. We performed calcium-imaging on individual cell bodies and the whole area within laminae I and II in spinal cord slices from mice in the naïve state or 24h following unilateral hindpaw plantar injection of complete Freund's adjuvant. Calcium signals evoked by dorsal root stimulation at varying strengths displayed a steep rise and slow decay over 15-20s and increased progressively with both increasing intensity and frequency of stimulation in naïve mice. Experiments with pharmacological inhibitors revealed that both ionotropic glutamate receptors and intracellular calcium stores contributed to maximal calcium signals in laminae I and II evoked by stimulating dorsal roots at 100Hz frequency. Importantly, as compared to naïve mice, we observed that in mice with unilateral hindpaw inflammation, calcium signals were potentiated to 159+/-10% in the ipsilateral dorsal horn and 179+/-8% in the contralateral dorsal horn. In addition to the contribution from NMDA receptors, GluR-A-containing AMPA receptors were found to be critically required for the above changes in spinal calcium signals, as revealed by analysis of genetically modified mouse mutants, whereas intracellular calcium release was not required. Thus, these results suggest that there is an important functional link between calcium signaling in superficial spinal laminae and the development of inflammatory pain. Furthermore, they highlight the importance of GluR-A-containing calcium-permeable AMPA receptors in activity-dependent plasticity in the spinal cord.


Cross-frequency coupling of frontal theta and posterior alpha is unrelated to the fidelity of visual long-term memory encoding.
Given that the encoding of information into visual long-term memory relies on multiple spatially distinct areas in the human brain, encoding into visual memory is a cognitive process likely to rely on networks formed via large-scale coupled neuronal oscillations. Previous research suggests that decreases in occipital alpha power and increases in mid-frontal theta power individually contribute to the encoding of retrievable representations in visual long-term memory. The present study asks whether these oscillations form a coupled network that operates during long-term memory encoding. Here we show that neither amplitude-amplitude coupling nor phase-amplitude coupling between frontal theta and posterior alpha are correlated with observers' subsequent memory when storing pictures in visual long-term memory. Correlations between alpha and theta power were stronger during eyes-open, resting-state periods when no task was performed than immediately following the presentation of a to-be-remembered picture. Finally, we also found that the strength of theta-alpha coupling was not modified by temporal lobe anodal transcranial direct current stimulation, despite observers showing enhanced memory for pictures behaviorally. Collectively, these findings indicate that posterior alpha and frontal theta activity are not simply component parts of a larger scale coupled network underlying visual memory.


Diabetes risk, low fitness, and energy insufficiency levels among children from poor families.
Low-income populations have higher rates of type 2 diabetes and it is the hope of the investigators to increase support for the dissemination of evidence-based prevention programs aimed at children from poor families. To determine the prevalence of high blood glucose, obesity, low fitness, and energy insufficiency levels among children from poor families. The cross-sectional study conducted in fall 2001 used fasting capillary glucose, body mass index, body fat, step test, and three 24-hour dietary recalls to assess diabetes risk factor levels. Participants were 1,402 fourth-grade students aged 8 to 10 years. The racial/ethnic backgrounds were 80% Mexican American, 10% African American, 5% Asian American, and 5% non-Hispanic white. All data were analyzed for descriptive statistics and frequencies of distribution. Means were computed by sex for all diabetes risk factors and t test conducted to determine differences between sexes. Nearly 75% of participants lived in households with <USD 20,400 annual income. Although 44% of students were energy insufficient, 33% were obese, and 7% had high blood glucose levels. Most of these students had marginal to unacceptable fitness levels and consumed high energy-dense and low nutrient-dense foods. Children living in poverty have high levels of diabetes risk factors and need early detection and intervention programs. Prudent advice might be to increase physical activity and intake of nutrient-dense foods rather than to restrict energy intake.


Adaptation to Antimicrobials and Pathogenicity in Mycoplasmas: Development of Ciprofloxacin-Resistance and Evolution of Virulence in Acholeplasma laidlawii.
For the first time it was shown that the development of resistance to ciprofloxacin in vitro in Acholeplasma laidlawii, a mycoplasma which is widely spread in nature and which is the main contaminant of cell cultures and vaccines, is associated with diverse pathways of virulence evolution: virulome and virulence differ significantly between ciprofloxacin-resistant strains, including those with the same level of antimicrobial resistance.


The defects in development and apoptosis of cardiomyocytes in mice lacking the transcriptional factor Pax-8.
Cardiac-specific deletion of ALK3 is lethal in mid-gestation with ventricular septum malformations (VSM). This study was designed to define the Pax-8's role in heart development and cardiomyocyte apoptosis. Pathologic changes in the hearts of Pax-8 or ALK3 knockout and wild type control mice were determined by light and electron microscopy. Analysis of cardiomyocyte apoptosis was performed by TUNEL. The effect of Pax-8 gene deficiency on caspase-3 activity was examined after transfecting Pax-8 siRNA into cultured myoblast cell line. Mice with ALK3 or Pax-8 gene knockout but not wild type control animals showed the development of VSM. Increased cardiomyocyte apoptosis was found in homozygotes. Echocardiography showed that Pax-8 homozygote mice developed malfunction of the heart. Furthermore, the caspase-3 activity was significantly higher in the cells treated with Pax-8 siRNA as compared to those treated with negative control siRNA in H9C2 (2-1) cell line. The Pax-8 gene may play a crucial role in heart development and regulating cardiocyte apoptosis. Knockout of Pax-8 may exert a similar effect on myocardial morphology and apoptosis as those seen in ALK3 knockouts. Furthermore, the ventricular septum malformations could be partially attributed to accelerated cardiomyocyte apoptosis.


An evaluation of illness, treatment perceptions, and depression in hospital- vs. home-based dialysis modalities.
Depressive symptoms are common among patients with end-stage renal disease (ESRD). In order to better understand what factors influence these symptoms, we examined the impact of illness and treatment cognitions on emotional adjustment and the influence of dialysis modality (hospital- vs. home-based dialysis) on this relationship. A cross-sectional sample of 145 ESRD patients on four different dialysis modalities [hospital hemodialysis (HD), n=52; home HD, n=25; continuous ambulatory peritoneal dialysis (CAPD), n=45; automated PD (APD), n=23] completed the Illness Perceptions Questionnaire, the Illness Effects Questionnaire, the Treatment Effects Questionnaire, and the Beck Depression Inventory. Measures of ESRD severity/comorbidity and biochemistry were also collected. Perceptions of treatment disruptiveness and attributions to poor medical care were significantly greater in CAPD. Home-based treatments were not found to confer an emotional adjustment advantage compared to hospital HD. There were marked differences across home-based modalities, with n=22 (44.4%) CAPD meeting the clinical cutoff of depression (≧16) vs. n=6 (26.1%) in APD and n=2 (8%) in home HD. After adjusting for case-mix differences, the mean levels of depressed mood remained significantly higher in CAPD patients compared to APD and home HD (P<.01). On multiple regression analysis, 42.5% of the variance in depression was explained by the End-Stage Renal Severity Index, dialysis modality, perceived treatment disruptiveness, and beliefs about illness consequences and the extent to which the illness could be controlled. The findings suggest that the benefits of self-care are not uniformly manifested across dialysis modalities and that patients' cognitions are important determinants of depressed mood with implications for future research and clinical practice.


Long-term survival of Escherichia coli O157 on pasture following an outbreak associated with sheep at a scout camp.
To monitor the decay of E. coli O157 in soil (loamy sand) on a scout campsite following an outbreak in humans. Samples of soil and sheep faeces were collected from the campsite and tested for the presence of E. coli O157 by immunomagnetic separation (IMS) after enrichment in buffered peptone water + vancomycin at 42 degrees C for 6 h. Enumeration of target was carried out by direct plating onto sorbitol MacConkey agar plates supplemented with cefixime and tellurite (CTSMAC) incubated at 37 degrees C for 24 h. Low numbers (< 100 g(-1)) were estimated by the most probable number (3-tube MPN) technique. Survival was observed for 15 weeks. A number of laboratory studies have followed the decay of E. coli O157 in soil, animal faeces and water. This study follows (for the first time) the decay of the organism in soil after an outbreak associated with sheep. It demonstrates the long-term persistence of the organism in the environment and the results will be potentially important in performing risk assessments for both human and animal infection.


Establishment of a human induced pluripotent stem cell line, JUCTCi012-A, from multiple symmetric lipomatosis (MSL) patient carrying a homozygous Arg707Trp (c.2119C > T) mutation in the MFN2 gene.
Induced pluripotent stem cells (iPSCs) were generated from skin fibroblasts collected from a 39-year-old multiple symmetric lipomatosis (MLS) female patient carrying a point mutation in MFN2 gene (c.2119C > T). The resulting iPSCs showed typical embryonic-like morphology, expressed pluripotency stem cell markers, retained the normal karyotype after reprogramming and showed the potential to differentiate into three germ layers. This iPSC line can be used for studying MSL disease mechanisms.


Investigation on the plasmon Talbot effect of finite-sized periodic arrays of metallic nanoapertures.
We present an in-depth and systematical investigation on the plasmon Talbot effect of finite-sized two-dimensional (2D) periodic metallic nanoaperture arrays. The nanoaperture shapes, fill factor, lattice distribution, array size, film thickness, material property and polarization state of the incident light are considered, and the inherent influencing rules are summarized via the three-dimensional (3D) finite-difference time-domain (FDTD) numerical simulations. The nanoaperture shapes, fill factor or array size seems to express a tiny influence on Talbot effect, which shows a good agreement with our previously reported experimental results. Besides, square lattice brings out a much more uniform Talbot pattern than the triangular distribution, and the smaller array period should be taken to estimate the Talbot distance when it comes to a rectangular distribution. Furthermore, the thickness of Au film is suggested to within the range of 50~100 nm, which gives a broadest Talbot contour. It is also found out that the elliptical shape of hotspots is closely related to the linearly polarization state of the light source, showing an asymmetric electromagnetic field. The research contributes to a better understanding of the optical transmission features through periodic metallic nanoaperture arrays, which provides opportunities for the potential applications such as nanofabrication, optoelectronics, and imaging.


Theta and alpha oscillations reflect differences in memory strategy and visual discrimination performance in patients with Parkinson's disease.
The aim of the present study was to investigate alterations in brain oscillatory activity during transient intentional encoding of abstract novel shapes in patients with Parkinson's disease (PD). Combined time-frequency analyses of alpha and theta power revealed a clear dissociation between PD patients (N=10) and age-matched healthy controls (N=10). PD patients used sub-optimal stimulus encoding strategies for subsequent maintenance and recall, whereas the controls mainly used categorization processes. In contrast to controls, PD patients showed significantly less theta increase and upper alpha suppression at frontal locations and significant laterality of early posterior theta and lower-2 alpha oscillations at right posterior locations. These findings suggest that the fronto-striatal circuits participate in visual categorization processes. Furthermore, theta and alpha oscillations appear to be involved in mediating the integration processes in mnemonic networks underlying visual categorization.


Dose volume histogram analysis of focal liver reaction in follow-up multiphasic CT following stereotactic body radiotherapy for small hepatocellular carcinoma.
To investigate threshold dose (TD) of focal liver reaction (FLR) following stereotactic body radiotherapy (SBRT) for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. In consecutive 50 patients receiving SBRT for small HCC, 38 patients receiving SBRT and follow up >6 months, FLR on follow-up CT had been previously studied. Patients with good concordance between FLR and highly irradiated area were eligible. Dose volume histogram (DVH) was used to identify TDs for FLR. Clinical factors were analyzed for correlation with TDs. Of 24 eligible patients, 23 had Child-Pugh score A and 1 scored B. Presence of FLR peaked at a median of 6 (range; 3-12) months. The median and 95% confidential intervals of TDs of pre-contrast and portal-venous phase CT were 32.4 Gy (30.3-35.4) and 34.4 Gy (31.9-36.0), respectively. Each median coefficient representing the concordance was 74.9% (range; 55.8-98.0%) and 80.5% (range; 70.8-92.4%), respectively. No clinical factors significantly correlated with the TDs. We proposed 30 Gy/5 fractions as TD of FLRs following SBRT for patients with HCC and liver cirrhosis. This TD will enable us to predict injured liver volume and to avoid complication beforehand from toxicity. Further pathological and clinical studies, in addition to more practical and precise data of DVH, are needed to clarify the significance of FLRs.


SIRT3 inhibition suppresses hypoxia-inducible factor 1α signaling and alleviates hypoxia-induced apoptosis of type B spermatogonia GC-2 cells.
Hypoxia has been reported to be an important factor leading to male infertility, and it has been reported that hypoxia can induce the apoptosis of mouse spermatogenic cells. Sirtuin 3 (SIRT3) has been reported to promote the degradation of hypoxia-inducible factor 1α (HIF-1α), and thus, we hypothesized that SIRT3 may influence hypoxia-induced apoptosis of spermatogonia. In this study, we overexpressed or inhibited SIRT3 in mouse type B spermatogonia GC-2 cells and then subjected the cells to hypoxia or normoxia, before examining hypoxia-responsive gene expression and cell viability. We report that SIRT3 stabilizes hypoxia-inducible factor 1α (HIF-1α) and activates its downstream target gene expression in GC-2 cells. We also show that the SIRT3 inhibitor 3-TYP suppresses HIF-1α target gene expression and alleviates hypoxia-induced apoptosis of GC-2 cells. Our study reveals the critical role and underlying mechanisms of SIRT3 in hypoxia-induced apoptosis of mouse type B spermatogonia GC-2 cells.


A review of the unique features of HDL apoproteins.
The human plasma high density lipoproteins (HDL) are a heterogeneous ensemble of five proteins associated with both neutral and polar lipids. The sequence of all five proteins are known. ApoA-I and apoA-II are the major protein components; apoC-I, apoC-II and apoC-III are the minor protein components. All these apoproteins spontaneously recombine with phospholipids to give stable lipid-protein complexes and freely exchange between the two major HDL subclasses, HDL2 and HDL3. In addition, ApoC-I, apoC-II, and apoC-III exchange between HDL and very low density lipoproteins. Furthermore, certain HDL apoproteins are activators for plasma enzymes that are important in lipid metabolism. ApoA-I and apoC-I activate lecithin/cholesterol acyltransferase; apoC-II is an activator of lipoprotein lipase. The regions of apoC-I and apoC-II that are involved in the activation of these enzymes have been localized with synthetic peptides. Studies of synthetic and native fragments of apoA-II, apoC-I, apoC-II, and apoC-III as well as model lipid-binding peptides have identified specific regions with structural features common to lipid-binding proteins. These special properties, which include helical potential, sequences with a critical amphipathic length, and high hydrophobicity of the nonpolar side of the amphipathic helix, are the determinants of HDL structure and metabolism.


Viral oncoproteins and ubiquitination: accessing a cellular toolbox for modifying protein function.
Human Papillomavirus oncoproteins directly target components of the Ubiquitin Proteasome System (UPS) and allow perturbation of multiple cellular processes linked to the control of apoptosis, transcription and innate immunity. This activity primarily creates an environment favourable for viral replication, but can contribute towards malignancy, thus highlighting the roles that manipulation of the UPS can play in the development of human cancers.


Innate lymphoid cells in intestinal immunity and inflammation.
Innate lymphoid cells (ILCs) are a new and distinct family of innate immune cells that play an important role in immunity and inflammation. In this review, we focus on the role of ILCs in mucosal tissues, especially in the gut, in health and disease. ILCs support intestinal homeostasis by protecting the intestine from pathogens, contributing to the development of gut lymphoid tissue, and helping to repair injuries. By cooperating with epithelial cells and other innate and adaptive immune cells, ILCs participate in the control of pathogens and tolerance of commensal bacteria. The development and maintenance of ILCs are influenced by nutrients and metabolites sourced from diet and/or gut bacteria. ILCs have been shown to be involved in host metabolism and to participate in various diseases of the intestine including infectious and chronic inflammatory diseases, and cancer. Thus, the elucidation of ILC biology provides an exciting potential for development of novel therapeutic means to modulate immune responses in various disease settings.


Assessment of the alveolar bone loss in fresh socket implant procedures with immediate implant loading via temporary preformed anatomical healing caps: Comparison of two different lengths of the implant collar.
The aim of the present clinical and radiologic retrospective study was to evaluate alveolar bone remodeling, in terms of alveolar width and peri‑implant bone level, two years after immediate implant positioning (with two different collar lengths, 0.8 mm and 2.0 mm) and loading of preformed healing cap. The Null hypothesis, H0 is: there was no difference between the two groups of implants. Patients suffering from single-tooth edentulous areas in premolar, cuspid, and incisive areas were treated with fresh-socket implants and immediate preformed anatomical healing caps. Each final crown restoration was fabricated 3 months later. Primary outcomes (related to loss of the alveolar width and peri‑implant bone level) and secondary outcomes (testing adverse events, and measuring implant/prosthesis survival) were acquired and analyzed. A two-year retrospective analysis was conducted on 31 patients (19 female and 12 male), who underwent dental implant placement with implants having two different lengths of the collar: group A, 0.8 mm, and group B, 2.0 mm. As for the width of the alveolar crest, there was a negligible loss (less than half a millimeter) reported for both the groups, anyway reaching a statistical significance. Preoperative alveolar widths (9.50±0.67 mm and 9.45±0.90 mm, respectively for groups A and B) were different from the two-year alveolar widths (9.20±0.74 mm and 8.93±0.99 mm, respectively for groups A and B) with p-values ≤ 0.0049. When the marginal bone loss was assessed, significant differences were registered between the two procedure groups (-1.42±0.34 mm for group A and -0.11±0.15 mm for group B with a p-value < 0.0001). The proper design of a healing abutment was very important to preserve the emergence profile immediately after extraction and implant placement. The length of the implant collar used with an immediate healing abutment appeared to affect the preservation of the alveolar crest with predictable final results.


Intraocular melanoma in the rat.
8 cases are reported of intraocular melanoma encountered in treated and untreated rats from 6 chronic toxicity studies.


The nicotine dependence phenotype, time to first cigarette, and larynx cancer risk.
Cigarette smoking is the major cause of laryngeal cancer. The time to first cigarette after waking in the morning is a behavior associated with several dimensions of nicotine dependence including the dose of smoke uptake. We hypothesized that a short TTFC increases the risk of laryngeal cancer. The analysis was based on data from a hospital-based case-control study of laryngeal cancer. The current analysis included only subjects who were ever cigarette smokers, including 570 cases and 343 controls (832 whites and 81 blacks). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression adjusting for smoking history and other potential confounders. Incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 1975 to 2006 were analyzed for trends in laryngeal cancer. There was a dose-response relationship between TTFC and supraglottic cancer. Compared to subjects who smoked more than 60 min after waking, the adjusted odds ratio was 1.51 (95% CI, 0.63-3.61) for 30-60 min and 3.13 (95% CI, 1.56-6.30) for 0-30 min. No association was observed between TTFC and cancer of the glottis. In blacks, the TTFC was not associated with the risk of laryngeal cancer. Trends in SEER rates were similar for cancer of the glottis and supraglottis, indicating that the site-specific differences were not affected by unknown confounders. A nicotine dependence behavior that is associated with cigarette smoke uptake increases the risk of cancer of the supraglottis larynx, but not glottis larynx.


Proposal for a new class within the phylum Proteobacteria, Acidithiobacillia classis nov., with the type order Acidithiobacillales, and emended description of the class Gammaproteobacteria.
The order Acidithiobacillales was previously assigned to the class Gammaproteobacteria. Recent analyses have indicated that this order actually lies outside all the proteobacterial classes, as a sister group to the combined classes Betaproteobacteria and Gammaproteobacteria. We now confirm this result with multiprotein phylogenetic analysis of all the available genomes of members of the order Acidithiobacillales and representatives of all available bacterial orders, and propose the new proteobacterial class, Acidithiobacillia, with the type order Acidithiobacillales, comprising the families Acidithiobacillaceae and Thermithiobacillaceae with the type genus Acidithiobacillus.


Oxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia.
Preeclampsia is a pregnancy-specific syndrome with multisystem involvement which leads to foetal, neonatal, and maternal morbidity and mortality. This syndrome is characterized by the onset of clinical signs and symptoms and delivery before (early-onset preeclampsia, eoPE), or after (late-onset preeclampsia, loPE), the 34 weeks of gestation. Preeclampsia is a mitochondrial disorder where its differential involvement in eoPE and loPE is unclear. Mitochondria regulate cell metabolism and are a significant source of reactive oxygen species (ROS). The syncytiotrophoblast in eoPE and loPE show altered mitochondrial structure and function resulting in ROS overproduction, oxidative stress, and cell damage and death. Mitochondrial dysfunction in eoPE may result from altered expression of several molecules, including dynamin-related protein 1 and mitofusins, compared with loPE where these factors are either reduced or unaltered. Equally, mitochondrial fusion/fission dynamics seem differentially modulated in eoPE and loPE. It is unclear whether the electron transport chain and oxidative phosphorylation are differentially altered in these two subgroups of preeclampsia. However, the activity of complex IV (cytochrome c oxidase) and the expression of essential proteins involved in the electron transport chain are reduced, leading to lower oxidative phosphorylation and mitochondrial respiration in the preeclamptic placenta. Interventional studies in patients with preeclampsia using the coenzyme Q10, a key molecule in the electron transport chain, suggest that agents that increase the antioxidative capacity of the placenta may be protective against preeclampsia development. In this review, the mitochondrial dysfunction in both eoPE and loPE is summarized. Therapeutic approaches are discussed in the context of contributing to the understanding of mitochondrial dysfunction in eoPE and loPE.


A 1H/19F minicoil NMR probe for solid-state NMR: application to 5-fluoroindoles.
We show that it is feasible to use a minicoil for solid-state 19F 1H NMR experiments that has short pulse widths, good RF homogeneity, and excellent signal-to-noise for small samples while using low power amplifiers typical to liquid-state NMR. The closely spaced resonant frequencies of 1H and 19F and the ubiquitous use of fluorine in modern plastics and electronic components present two major challenges in the design of a high-sensitivity, high-field 1H/19F probe. Through the selection of specific components, circuit design, and pulse sequence, we were able to build a probe that has low 19F background and excellent separation of 1H and 19F signals. We determine the principle components of the chemical shift anisotropy tensor of 5-fluoroindole-3-acetic acid (5FIAA) and 5-fluorotryptophan. We also solve the crystal structure of 5FIAA, determine the orientation dependence of the chemical shift of a single crystal of 5FIAA, and predict the 19F chemical shift based on the orientation of the fluorine in the crystal. The results show that this 1H/19F probe is suitable for solid-state NMR experiments with low amounts of biological molecules that have been labeled with 19F.


Induction of neurogenic tumors by nitrosotrialkylureas in rats.
Four nitrosotrialkylureas were each fed to groups of 15 male and 15 female Sprague-Dawley rats for 50 weeks in drinking water at the same molar concentration. Tumors of nervous origin arose after treatment with nitrosotrimethylurea (3/30), notrosotriethylurea (7/30), nitrosomethyldiethylurea (23/30), and nitrosoethyldimethylurea (8/30). A comparison of the relative stabilities of the four nitrosoureas in aqueous solution at various pH's showed no correlation with the tumorigenicities of the compounds.


Time trend in height, weight, and obesity prevalence in school children from Northern France, 1992-2000.
The aim of this study was to evaluate the changes in height, weight and in the prevalence of overweight and obesity between 1992 and 2000 in children living in two towns of northern France. Two cross-sectional studies were performed in every pre-school (last section) and primary schools of the two towns in 1992 (383 girls and 421 boys enrolled) and 2000 (296 girls and 305 boys). Children were 5 to 12 year old in both studies. Body height and weight were measured, and BMI was calculated (weight/height(2)). Prevalence of overweight and obesity was determined according to the gender- and age- specific cut-offs of the new international reference (IOTF). We also used the 90(th) and the 97(th) percentiles of the French reference gender- and age-specific BMI curves to define two grades of overweight. After adjustment for age, boys were on average 1.5 cm taller in 2000 than in 1992 (p<0.001), and the same trend was observed in girls (+ 0.9 cm, p<0.075). Height-adjusted or age-adjusted weight and BMI were significantly higher in 2000 than in 1992. In girls, obesity defined by IOTF criteria increased from 1.6 to 4.4% (p<0.03) and overweight from 14.1 to 18.6% (p<0.11). In boys, the change in prevalences was significant only when the less stringent criteria (i.e. the 90(th) percentile of French references) was used (13.8% in 1992 vs 20% in 2000, p=0.03). Over an 8 years period, there was an increase in height and BMI in both boys and girls. These results show that the increase in the prevalence of obesity is accompanied by a global trend of accelerated growth.


Tannins from Terminalia chebula fruits attenuates GABA antagonist-induced anxiety-like behaviour via modulation of neurotransmitters.
This article investigates the anxiolytic activity of Terminalia chebula tannin-rich extract against picrotoxin (PTX; GABA antagonist)-induced anxiety in mice model. Anxiolytic activity was studied by elevated plus maze (EPM), open field test (OFT), light/dark box test (LDT) and Vogel's conflict test (VCT). Electroencephalogram (EEG) was performed to know the changes in brain activity instigated by GABA antagonist. 5-hydroxytryptamine (5-HT), dopamine and norepinephrine levels in brain tissues were estimated by HPLC. The mRNA (CREB, BDNF, GABA, and 5-HT1A ) and protein expression (CREB, p-CREB, BDNF, ERK ½, p-ERK ½, GABAA Rα1, 5-HT1A and GAPDH) levels in brain tissue were determined by RT-PCR and Western blot analysis, respectively. Terminalia chebula tannin-rich extract (TCHE) supplementation increased locomotion in mice towards open arm (EPM), time spent in illuminated area (LDT), rearing frequency (OFT) and number of shocks (VCT) compared to PTX (P < 0.05). Furthermore, TCHE down-regulated serum cortisol levels and showed increased levels of 5-HT, DA and NE. Gene expressions such as BDNF, CREB, GABAA and 5-HT1A were up-regulated by TCHE treatment compared to PTX. Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.


Differences in Baseline Characteristics and Outcome Among Responders, Late Responders, and Never-Responders After Anterior Cruciate Ligament Reconstruction.
Loss to follow-up in registry studies might affect generalizability and interpretation of results. To evaluate the effect of nonresponder bias in our anterior cruciate ligament (ACL) registry. Case-control study; Level of evidence, 3. A total of 2042 patients with ACL reconstruction in the Hospital for Special Surgery ACL Registry between 2009 and 2013 were included in the study. Patients who completed the patient-reported outcome measures at 2 or 5 years were considered responders (n = 808). Baseline data and patient characteristics were compared between responders and nonresponders (n = 1234). Both responders and nonresponders were contacted and invited to complete the International Knee Documentation Committee (IKDC) and Marx scores electronically and respond to questions regarding return to sports and subsequent surgeries. Nonresponders who completed the questionnaires after reminders were considered late responders. The remaining nonresponders were considered never-responders. The late responders (n = 367) completed the questionnaires after a mean follow-up of 7.8 years (range, 6.7-9.6 years), while follow-up for the responders was 6.8 years (range, 5.0-9.7 years). Responders and late responders were then compared in terms of differences in IKDC and Marx scores from baseline to final follow-up. Nonresponders were younger (28.5 vs 31.5 years; P < .001) and more often male (60% vs 53%; P = .003) compared with responders. Responders had a higher level of education and were more likely to be White (79% vs 74%; P = .04). There were no substantial differences in patient characteristics or baseline IKDC and Marx scores between the late responders and never-responders. There were no statistically significant differences in patient-reported outcomes, return to sports, or subsequent surgeries between responders and late responders at a mean follow-up time of 8.8 years (range, 6.7-9.7 years). Repeat email reminders and telephone calls increased response rate by 18% (from 40% to 58%). There was no difference in clinical outcome as evaluated using IKDC and Marx scores between responders and late responders.


Multifactorial modeling, drug interactions, liver damage and aging.
A well designed physiological flow model can be used not only to describe and analyze the basic elimination of a drug but also it can form the basis for multifactorial analysis in situations of multiple organ dysfunction and drug therapy. Physiological flow models use existent knowledge of anatomical structure and physiological processes along with the biochemical basis of drug elimination to calculate concentration-vs-time profiles of drugs in various organs and tissue regions. A tissue region or organ must be included in the model if it is an important site of storage, toxicity, elimination, or other significant pharmacological action. Such models can be a powerful tool in medicine providing a rational basis for multiple drug therapy in high risk patients with altered organ function--especially for drugs with a narrow margin of safety. For some specific types of drug systems, physiological flow model models exist which can accurately describe drug concentration profiles in tissues for a variety of situations. A definitive general model is theoretically possible; but, in practice, has not yet been developed. Future research could provide the necessary information to make multifactorial analysis a clinically useful tool in rational drug therapy.


Alterations in heart rate following radiofrequency ablation in the treatment of reentrant supraventricular arrhythmias: relation to alterations in autonomic tone.
To determine the relation between the creation of endocardial lesions and alterations in autonomic tone, we analyzed heart rate variability in patients undergoing radiofrequency catheter ablation for symptomatic supraventricular tachycardia. Elevated heart rates are frequently noted after radiofrequency catheter ablation for supraventricular arrhythmias. It has been postulated that this elevation may be secondary to alterations in cardiac autonomic tone. Since heart rate variability is a measure of autonomic nervous system activity, we used this technique to examine the heart rate elevation and to characterize postablation autonomic changes. Thirty-eight patients undergoing 44 radiofrequency catheter ablation procedures were included in the study. Total arrhythmic substrates treated included 34 accessory pathways and 13 AV nodes with dual physiology. Twenty-four hour ambulatory electrocardiographic recordings were obtained in a drug-free state prior to, ablation early postablation, and late postablation. Spectral and nonspectral analyses of heart rate variability were performed. Subgroup analyses were also done on specific cohorts. Subgroups included patients undergoing accessory pathway ablations, AV node modifications, and ablation of septal and nonseptal targets. To determine whether the amount of tissue damage was related to changes in heart rate variability, we analyzed the relation between the total energy delivered to the endocardium and the peak change in creatine kinase and heart rate variability. In this population, a significant transient increase in heart rate was noted following radiofrequency ablation. All time and frequency domain parameters of heart rate variability showed significant reversible decreases. These changes were independent of target site and arrhythmia substrate. There was no correlation noted between the changes in heart rate variability and either the total amount of energy applied to the endocardium or the change in creatine kinase. Increased heart rates and decreased heart rate variability occur following radiofrequency catheter ablation for supraventricular tachycardia. Clinically, the predominant effect is that of decreased parasympathetic tone. Since these transient changes are independent of arrhythmic substrate or ablation site in the atria, a rich parasympathetic innervation of the heart is proposed.


Prognostic implication of downregulated exosomal miRNAs in patients with sepsis: a cross-sectional study with bioinformatics analysis.
Despite the understanding of sepsis-induced extracellular vesicles (EVs), such as exosomes, and their role in intercellular communication during sepsis, little is known about EV contents such as microRNA (miRNA), which modulate important cellular processes contributing to sepsis in body fluids. This study aimed to analyze the differential expression of exosomal miRNAs in plasma samples collected from sepsis patients and healthy controls, and to identify potential miRNA regulatory pathways contributing to sepsis pathogenesis. Quantitative real-time PCR-based microarrays were used to profile plasma exosomal miRNA expression levels in 135 patients with sepsis and 11 healthy controls from an ongoing prospective registry of critically ill adult patients admitted to the intensive care unit. The identified exosomal miRNAs were tested in an external validation cohort (35 sepsis patients and 10 healthy controls). And then, functional enrichment analyses of gene ontology, KEGG pathway analysis, and protein-protein interaction network and cluster analyses were performed based on the potential target genes of the grouped miRNAs. Finally, to evaluate the performance of the identified exosomal miRNAs in predicting in-hospital and 90-day mortalities of sepsis patients, receiver operating characteristic curve (ROC) and Kaplan-Meier analyses were performed. Compared with healthy controls, plasma exosomes from sepsis patients showed significant changes in 25 miRNAs; eight miRNAs were upregulated and 17 downregulated. Additionally, the levels of hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p were significantly lower in sepsis patients than in healthy controls (p < 0.0001). These four miRNAs were confirmed in an external validation cohort. In addition, the most common pathway for these four miRNAs were PI3K-Akt and mitogen-activated protein kinase (MAPK) signaling pathways based on the KEGG analysis. The area under the ROC of hsa-let-7f-5p, miR-331-3p, miR-301a-3p, and miR-335-5p level for in-hospital mortality was 0.913, 0.931, 0.929, and 0.957, respectively (p < 0.001), as confirmed in an external validation cohort. Also, the Kaplan-Meier analysis showed a significant difference in 90-day mortality between sepsis patients with high and low miR-335-5p, miR-301a-3p, hsa-let-7f-5p, and miR-331-3p levels (p < 0.001, log-rank test). Among the differentially-expressed miRNAs detected in microarrays, the top four downregulated exosomal miRNAs (hsa-let-7f-5p, miR-331-3p miR-301a-3p, and miR-335-5p) were identified as independent prognostic factors for in-hospital and 90-day mortalities among sepsis patients. Bioinformatics analysis demonstrated that these four microRNAs might provide a significant contribution to sepsis pathogenesis through PI3K-Akt and MAPK signaling pathway.


An online tumor board with international neurosurgical collaboration guides surgical decision-making in Western Kenya.
Telecollaboration via web-based platforms has emerged as a tool to relieve constraints on the establishment of tumor boards for neurosurgical oncology. Challenging tumor cases arising in low- and middle-income countries may benefit from the use of such models. The case of a 5-year-old boy presenting in Western Kenya with a challenging tumor and symptomatic hydrocephalus was presented on a novel web platform to a multi-national audience of neurosurgeons. The treating neurosurgeon invited a physician network to review the case vignette and radiographic images. Respondents independently offered input during a prescribed response period. Three respondents provided surgical opinions during a 24-h response period. The treating neurosurgeon utilized the pooled input to determine a course of action for the patient. When a web-based platform is available, lone neurosurgeons in low-resource settings may nevertheless apply multi-national, multi-institutional perspectives to challenging oncology cases.


Proximal dendritic localization of NALCN channels underlies tonic and burst firing in nigral dopaminergic neurons.
In multipolar nigral dopamine (DA) neurons, the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. However, the causal link between them is unknown. Here we report that the proximal dendritic localization of NALCN underlies pacemaking and burst firing in DA neurons. Our morphological analysis of nigral DA neurons reveals that TRPC3 is ubiquitously expressed in the whole somatodendritic compartment, but NALCN is localized within the PDCs. Blocking either TRPC3 or NALCN channels abolished pacemaking. However, only blocking NALCN, not TRPC3, degraded burst discharges. Furthermore, local glutamate uncaging readily induced burst discharges within the PDCs, compared with other parts of the neuron, and NALCN channel inhibition dissipated burst generation, indicating the importance of NALCN to the high excitability of PDCs. Therefore, we conclude that PDCs serve as a common base for tonic and burst firing in nigral DA neurons. KEY POINTS: Midbrain dopamine (DA) neurons are slow pacemakers that can generate tonic and burst firings, and the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. We find that slow tonic firing depends on the basal activity of both the NALCN and TRPC3 channels, but that burst firing does not require TRPC3 channels but relies only on NALCN channels. We find that TRPC3 is ubiquitously expressed in the entire somatodendritic compartment, but that NALCN exists only within the PDCs in nigral DA neurons. We show that NALCN channel localization confers high excitability on PDCs and is essential for burst generation in nigral DA neurons. These results suggest that PDCs serve as a common base for tonic and burst firing in nigral DA neurons.


The strategy of treatment of Hodgkin's disease.
The treatment of Hodgkin's disease necessitates, in most cases, an association of radiotherapy for the macroscopic tumoral masses and chemotherapy for the cells generalized in the organism. Whenever a systematic chemotherapy is associated with radiotherapy, a precise staging topography with laparotomy is useless. The current therapeutic trials should seek methods to lighten these treatments by determining the best equilibrium between the two principal methods and by specifying the ventual place of immunotherapy. The present possibility of curing more than three-fourths of Hodgkin's patients incites us to look for means of reducing the treatment and its inconveniences for the curable forms, and search for more active or tolerable treatments for the uncurable forms.


Tuberculosis of the hand.
Eleven cases of tuberculous infection affecting the hand are presented. The age incidence, clinical presentations and investigations are discussed. Treatment includes chemotherapy, radical synovectomy and early mobilisation. Hand function after surgery in the follow-up period of three to twenty-one months was very satisfactory with the exception of three cases which presented at a very late stage with secondary involvement of the wrists. The confusion that exists while using such terms as "Tuberculous Dactylitis" and "Tuberculous Tenosynovitis" is discussed. An alternative suggestion is made that "Tuberculosis of the Hand" be used.


The relationship between reported daily nicotine dose from NRT and daily cigarette consumption in pregnant women who smoke in an observational cohort study.
For non-pregnant people unable to quit smoking, the NHS recommends nicotine replacement therapy (NRT) for smoking reduction. This is not recommended during pregnancy due to concerns about higher nicotine intake than smoking alone. We investigated the relationship between daily nicotine dose from NRT and cigarette consumption reported by pregnant women receiving smoking cessation support. We conducted secondary analysis of data from currently smoking pregnant women, recruited from antenatal clinics (Nottingham University Hospitals, UK) or online between June 2019-September 2020. Participants set a quit date, received a prototype NRT adherence intervention, and reported cigarettes per day (CPD) and daily NRT dose (mg) via smartphone app for 28 days. 388 women were screened, 32 (8%) were eligible and joined the study. 24 (75%) submitted 510 app reports in total. 17 (71%) reported smoking and using NRT concurrently on at least one day, with concurrent use reported on 109 (21%) of app reports.The relationship between daily NRT dose and CPD followed an exponential decay curve of approximately 7%. In multilevel repeated measures modelling using 4 linear splines (knots 17, 40 and 85 mg/NRT), significant fixed effects of daily NRT dose on CPD were observed for splines 1, 3 and 4. The strongest association was spline 1 (0-17 mg/NRT), where each 10mg NRT increase was associated with a 0.6 CPD reduction (24% on average). Among women in a cessation study, many smoked and used NRT concurrently; within these women, daily nicotine dose and heaviness of smoking were inversely related. Findings have implications for the design of future interventions intended to reduce harm associated with smoking in pregnancy. They suggest using NRT alongside smoking in pregnancy could help some women reduce the number of cigarettes they smoke per day.


Broad-spectrum cytotoxicity to cancer cells of Brevilaterin C from Brevibacillus laterosporus and its specific mechanism on human epidermal cancer cells.
Antimicrobial peptides (AMP) from Brevibacillus laterosporus have good prospects as clinical treatments for cancer. Nevertheless, details about their anticancer spectrum and mode of cytotoxicity remain poorly understood. A newly found AMP (named Brevilaterin C) secreted by B. laterosporus S62-9 exhibited strong inhibition on almost cancer cell lines examined at a concentration of 8 µg/ml but was relatively safe for normal cells. We further systematically examined its cytotoxicity and mechanism toward human epidermal cancer cell A431. A dosage of 3 µg/ml of Brevilaterin C could significantly increase lactate dehydrogenase release of tumor cells. Moreover, it could remarkably increase the ratio of apoptosis and reactive oxygen species generation of A431, indicating effective induction of apoptosis. Moreover, the formation of JC-1 aggregates was effectively prevented by a low concentration of Brevilaterin C, indicating its effective induction of A431's apoptosis. Brevilaterin C exhibited broad-spectrum cytotoxicity to cancer cells, indicating a good potential prospect in the medical field.


Morphine enhances hedonic taste palatability in rats.
The question of whether opiates stimulate feeding by enhancing taste pleasure was investigated by examining the effect of morphine upon hedonic and aversive reactions to taste (tongue protrusions, gapes, etc.). Rats (n = 12) were given SC injections of morphine (4 mg/kg) or equal volumes of isotonic saline 2 h after the start of their daily light cycle. Food intake was measured in a 2-h test. On days when they were given morphine, rats ate significantly more food than when given saline. Hedonic and aversive taste reactions were elicited by an infusion of sucrose-quinine solution into the mouth and were measured subsequently in a slow-motion video analysis. The same rats that showed an increase in food intake after treatment with morphine showed a significant increase in their positive hedonic responses. Aversive reactions were unchanged by morphine. The results support the hypothesis that morphine enhances feeding by increasing the hedonic palatability of food.


Hormonal assessment of participants in a long distance walk.
Exercise can disrupt homeostasis and trigger many adaptive responses in different hormonal axes. The study of hormonal interactions with physical activity is highly complex due to the number of variables, such as exercise duration, exercise intensity, individual level of training, circadian rhythm, nutritional status, and environmental conditions. This study was performed to assess daily variations of thyroid hormones, cortisol, testosterone, insulin and glucose during moderate to high intensity aerobic physical activity for 5 consecutive days. Sample collection was performed at baseline in the morning and in the evening, immediately after finishing the activity, on the 4 initial days of the activity. Statistical analysis was performed using software STATA V14. Continuous variables are presented as means and standard deviations, while categorical variables are presented as absolute and percentage values. We used Shapiro-Wilk, Wilcoxon Sign, Mann-Whitney and Student's T test, according the needs. The adrenocorticotropic axis showed an initial increase in the evening cortisol level compared to the baseline level in the morning (17.46 μg/dL and 15.97 μg/dL, respectively) and then exhibited a significant reduction between the 1st and 4th day of activity (17.46 μg/dL and 8.39 μg/dL, respectively; P = 0.001). The same pattern was observed for free thyroxine (T4) between the 1st and 4th day (1.31 and 1.14, respectively; P < 0.001). Moderate to intense long duration physical activity resulted in little variation in the hormones assessed, with a trend toward reduced levels of cortisol and free T4. These findings highlight an adaptive hormonal mechanism in response to stress that is repeated daily, as shown by cortisol and thyroid function in our study.


Aortic dissection with extension to a patent ductus arteriosus.
An 81-year-old woman presented with shortness of breath and fever of 3 days duration. An enhanced CT of the chest revealed a patent ductus arteriosus (PDA) communicating with the true lumen of an aortic arch dissection. Neither the aortic dissection nor the PDA was suspected. The patient had no history of a connective tissue abnormality or other condition which would predispose to dissection other than systemic hypertension. It is likely that propagation of the aortic dissection partially re-opened the ductus arteriosus.


CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA.
Triple-negative breast cancer (TNBC) is a molecular subtype with an unfavorable prognosis, and metastasis is the main reason for the failure of clinical treatment. However, the expression profile and regulatory function of circRNAs in TNBC progression are not fully understood. Herein, we performed high-throughput RNA-seq in paired breast cancer tissues and adjacent normal tissues and discovered a novel circRNA, circEIF3H, which was upregulated in breast cancer tissues. Large cohort survival analysis confirmed the association between high circEIF3H expression and poor prognosis of TNBC, indicating the vital function of circEIF3H in TNBC progression. Then we conducted both in vitro and in vivo experiments which illustrated that circEIF3H was essential for TNBC proliferation and metastasis. Further experiments showed that circEIF3H did not function as a microRNA sponge as in the most well-established pathway, but as a scaffold for IGF2BP2 and HuR to regulate the mRNA stability of HSPD1, RBM8A, and G3BP1. Our findings provide insight into a novel circRNA, circEIF3H, with significant cancer-promoting function via serving as a scaffold for IGF2BP2/HuR. These results identified circEIF3H as a potential target for developing individualized therapy of TNBC in the approaching future.


In vitro sensitivity of environmental isolates of pathogenic dematiaceous fungi to azole compounds and a phenylpropyl-morpholine derivative.
The in vitro sensitivity (minimum inhibitory concentrations; MICs) of 42 environmental isolates of pathogenic dematiaceous fungi to 7 azole compounds, viz. thiabendazole, ketoconazole, miconazole, econazole bifonazole, Bay n 7133, Bay 1 9139 and phenylpropyl-morpholine derivative, Ro14-4767/002 was studied by an agar dilution method using Emmon's Sabouraud dextrose agar (ESDA) as the culture medium. The isolates of Fonsecaea pedrosoi, Cladosporium carrionii, Exophiala jeanselmei and Ramichloridium subulatum were most sensitive to bifonazole with mean MICs of 0.06 microgram/ml or less; Phialophora verrucosa had an MIC of 0.05 microgram/ml to ketoconazole and Ro14-4767/002, respectively. Ochroconis sp had an MIC of 0.025 microgram/ml to Ro14-4767/002 and Cladosporium tennuisimum 0.39 microgram/ml to ketoconazole. Econazole and thiabendazole also showed good antifungal activity. The fungi were relatively resistant to the more recently developed azoles, viz. Bay n 7133 and Bay 1 9139, the later failing to inhibit C. tennuisimum at a concentration of 100 micrograms/ml. The minimum fungicidal concentrations (MFC) of the drugs were mostly within 2 to 8 fold of the MICs.


Analysis of Endogenous Spectral Power of EEG Alpha-Range Biopotentials during Mnestic Activity under Conditions of Rhythmically Organized Optical Stimulation.
We studied the effect of optical stimulation (10 Hz) on the effectiveness of mnestic activity in the n-back task in healthy subjects (n=32). EEG was recorded at all stages of the examination. The absolute values of the spectral power of the 10 Hz frequency (μV2) of the alpha range were calculated. According to the results of the test without optical stimulation, the examinees were divided into groups with high (group 1) and low (group 2) task performance. In the initial state, the spectral power of 10 Hz was significantly higher in group 1 subjects. Under conditions of screen flickering, the results became poorer in group 1 and better in group 2 in comparison with the results under normal conditions. These changes were accompanied by an increase in the spectral power of 10 Hz only in group 2 subjects. These findings can provide the basis for the development of practical recommendations for improving the mnestic functions in patients with consideration for the individual characteristics of their initial EEG.


Age of diagnosis clinically differentiates atypical teratoid/rhabdoid tumors diagnosed below age of 3 years: a database study.
Atypical teratoid/rhabdoid tumor (ATRT) is a rare and largely pediatric diagnosis, with poor survival. Diagnosis below the age of 3 years is characteristically seen as a poor prognostic sign. However, elucidating if clinical differences exist within this niche age group has never been attempted before. Correspondingly, we sought to characterize clinical profile of ATRT diagnoses before the age of 3 years based on separate ages of diagnosis. All pediatric ATRT patients aged < 3 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Age groups were divided based on diagnoses at ages 0-1 years in group 1, 1-2 years in group 2, and 2-3 years in group 3. Data were summarized, and overall survival (OS) was modeled using Kaplan-Meier and Cox regression analyses. A total of 354 ATRT diagnoses were made before the age of 3 years, with surgery used in 316 (89%) cases, chemotherapy in 242 (68%) cases, and radiation therapy in 118 (33%) cases. In terms of diagnosis age, there were 153 (43%) in group 1, 137 (39%) in group 2, and 64 (18%) in group 3. With respect to OS, median value was 9.9 months in group 1, 28.4 months in group 2, and 15.9 months in group 3. Upon multivariate analysis, receiving radiation therapy was the only parameter shared amongst all three groups as independently prognostic of longer OS (HR 0.53, P = 0.01 in group 1; HR 0.34, P < 0.01 in group 2; HR 0.31, P < 0.01 in group 3). In group 1, surgery (HR 0.47, P < 0.01) and chemotherapy (HR 0.44, P < 0.01) were also independently prognostic of longer OS. In group 3, multiple socioeconomic parameters were identified to independently predict longer OS. There were no additional predictive parameters identified in group 2. Although ATRT diagnosed before the age of 3 is typically viewed a poor prognostic age category, our findings demonstrate that the clinical profile of this pediatric niche is highly heterogeneous based on age of diagnosis. Survival of only those diagnosed between 0 and 1 years is independently prognosticated by all three treatment modalities; patients diagnosed between 1 and 2 years trend towards longest survival, and socioeconomic parameters are most influential in those diagnosed between 2 and 3 years.


Sensitive detection of CD147/EMMPRIN and its expression on cancer cells with electrochemical technique.
Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), plays an essential role in tumor progression and metastasis, the expression of which on cell surface is a critical clinical testing index for cancer therapy. In this work, an electrochemical method to assay CD147/EMMPRIN expression on tumor cell surface is proposed. While the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by horseradish peroxidase (HRP) can be employed for electrochemical measurement, the signal enhancement amplified by gold nanoparticles (GNPs) can be also utilized in this study. Therefore, under optimized conditions, the fabricated biosensor responds linearly to the CD147/EMMPRIN concentration from 125 to 1000 pg/mL with a detection limit as low as 52 pg/mL. High sensitivity can also be achieved for the quantification of breast cancer cells in a linear range from 6.2 × 10(4) to 6.25 × 10(5) cells/mL. Moreover, the CD147/EMMPRIN expressed on a single breast cancer cell can be calculated as 2.57 × 10(4) molecules/cell. The proposed strategy in this study is considerably potential for monitoring the dynamic protein expression on cancer cells and for the effective cancer diagnosis and treatment in the future.


Purification and properties of tyrosyl tRNA synthetase of rat liver.
Purification of rat liver tyrosine tRNA synthetase yields two protein fractions A and B and both fractions are required for charging of tyrosine to tRNAtyr. Fraction B catalyzes the activation of tyrosine. Fractions A and B have been purified to near homogeneity and they are composed of single polypeptide chains of 62,000 daltons each. Gel filtration studies suggest a molecular weight of 120,000 for the synthetase.


Synthesis and Biological Evaluation of Pyrroloindolines as Positive Allosteric Modulators of the α1β2γ2 GABAA Receptor.
γ-Aminobutyric acid type A (GABAA) receptors are key mediators of central inhibitory neurotransmission and have been implicated in several disorders of the central nervous system. Some positive allosteric modulators (PAMs) of this receptor provide great therapeutic benefits to patients. However, adverse effects remain a challenge. Selective targeting of GABAA receptors could mitigate this problem. Here, we describe the synthesis and functional evaluation of a novel series of pyrroloindolines that display significant modulation of the GABAA receptor, acting as PAMs. We found that halogen incorporation at the C5 position greatly increased the PAM potency relative to the parent ligand, while substitutions at other positions generally decreased potency. Mutagenesis studies suggest that the binding site lies at the top of the transmembrane domain.


Kinetics of glucose transport in human erythrocytes.
The rate of unidirectional D-[14C]glucose efflux from human red blood cells was determined at self-exchange and net-efflux conditions by means of the Millipore-Swinnex filtering technique and the rapid continuous flow tube technique with which initial rates can be measured within fractions of a second. Determinations at 38, 25 and 10 degrees C of the concentration dependence of glucose self-exchange flux and net efflux showed that both self exchange and net efflux followed simple Michaelis-Menten kinetics at all temperatures. At 38 degrees C the maximal self-exchange flux and the maximal net efflux were identical (6 X 10(-10) mol/cm2.sec). The cellular glucose concentration for half-maximal flux (K1/2) was 6.7 mM for self exchange and 8.2 mM for net efflux. By lowering temperature the maximal glucose self-exchange flux progressively exceeded the maximal net efflux, and was about three times larger at 10 degrees C. K1/2 for self exchange increased to 12.6 mM at 10 degrees C, while K1/2 for net efflux decreased to 4.4 mM. At 38 degrees C the glucose permeability at self exchange at a constant extracellular glucose concentration of 40 mM showed a bell-shaped pH dependence between pH 6 and pH 9. A maximum was found at pH 7.2, whereas the apparent permeability coefficient was halved both at pH 6 and pH 9. The temperature dependence of glucose transport was determined between 47 and 0 degrees C at a cellular glucose concentration of 100 mM which ensured greater than 85% saturation of the glucose transport system within the temperature range. The Arrhenius activation energy of glucose transport was not constant. By lowering the temperature, the activation energy increased gradually for net efflux from 55 kJ/mole between 38 and 47 degrees C to 151 kJ/mole between 0 and 10 degrees C. The temperature dependence of self-exchange flux showed a more pronounced change around 10 degrees C. The Arrhenius activation energy was found to be 61 kJ/mole above and 120 kJ/mole below 10 degrees C.


Semi-volatile components of PM2.5 in an urban environment: volatility profiles and associated oxidative potential.
The volatility profiles of PM2.5 semi-volatile compounds and relationships to the oxidative potential of urban airborne particles were investigated in central Los Angeles, CA. Ambient and thermodenuded fine (PM2.5) particles were collected during both warm and cold seasons by employing the Versatile Aerosol Concentration Enrichment System (VACES) combined with a thermodenuder. When operated at 50 °C and 100 °C, the VACES/thermodenuder system removed about 50% and 75% of the PM2.5 volume concentration, respectively. Most of the quantified PM2.5 semi-volatile species including organic carbon (OC), water soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), organic acids, n-alkanes, and levoglucosan, as well as inorganic ions (i.e., nitrate, sulfate, and ammonium) exhibited concentration losses in the ranges of 40-66% and 67-92%, respectively, as the thermodenuder temperature increased to 50 °C and 100 °C. Species in the PM2.5 such as elemental carbon (EC) and inorganic elements (including trace metals) were minimally impacted by the heating process - thus can be considered refractory. On average, nearly half of the PM2.5 oxidative potential (as measured by the dichlorodihydrofluorescein (DCFH) alveolar macrophage in vitro assay) was associated with the semi-volatile species removed by heating the aerosols to only 50 °C, highlighting the importance of this quite volatile compartment to the ambient PM2.5 toxicity. The fraction of PM2.5 oxidative potential lost upon heating the aerosols to 100 °C further increased to around 75-85%. Furthermore, we document statistically significant correlations between the PM2.5 oxidative potential and different semi-volatile organic compounds originating from primary and secondary sources, including OC (Rwarm, and Rcold) (0.86, and 0.74), WSOC (0.60, and 0.98), PAHs (0.88, and 0.76), organic acids (0.76, and 0.88), and n-alkanes (0.67, and 0.83) in warm and cold seasons, respectively, while a strong correlation between oxidative potential and levoglucosan, a tracer of biomass burning, was observed only during the cold season (Rcold=0.81).


The hepatic stem cell niche: identification by label-retaining cell assay.
Label retention assays remain the state-of-the-art approach to identify the location of intraorgan epithelial stem cell niches, in situ and in vivo. They are commonly used in organs with rapid cell turnover but have not been applied to the liver, where cell turnover is very slow. We used a sublethal dose of acetaminophen administered coincident with bromodeoxyuridine to load possible hepatic stem cells in mice with label and then administered a second, sublethal chase of acetaminophen to accomplish "washout" of label from transit amplifying cell populations. Four possible hepatic stem cell niches are identified by this approach: the canal of Hering (proximal biliary tree), intralobular bile ducts, periductal "null" mononuclear cells, and peribiliary hepatocytes. These results confirm several different and often contradictory lines of investigation regarding the intrahepatic location of stem/progenitor cells and suggest that the liver has a multi-tiered, flexible system of regeneration rather than a single stem/progenitor cell location.