Hemodynamic deterioration during extracorporeal membrane oxygenation weaning in a patient with a total artificial heart.
The Total Artificial Heart (Syncardia, Tucson, AZ) is approved for use as a bridge-to-transplant or destination therapy in patients who have irreversible end-stage biventricular heart failure. We present a unique case, in which the inferior vena cava compression by a total artificial heart was initially masked for days by the concurrent placement of an extracorporeal membrane oxygenation cannula. This is the case of a 33-year-old man admitted to our institution with recurrent episodes of ventricular tachycardia requiring emergent total artificial heart and venovenous extracorporeal membrane oxygenation placement. This interesting scenario highlights the importance for critical care physicians to have an understanding of exact anatomical localization of a total artificial heart, extracorporeal membrane oxygenation, and their potential interactions. In total artificial heart patients with hemodynamic compromise or reduced device filling, consideration should always be given to venous inflow compression, particularly in those with smaller body surface area. Transesophageal echocardiogram is a readily available diagnostic tool that must be considered standard of care, not only in the operating room but also in the ICU, when dealing with this complex subpopulation of cardiac patients.


Application of an implantable stimulator in the rehabilitation of paraplegic patients.
The surgical problems of implantable systems for functional electrical stimulation in the rehabilitation of plegic patients have been discussed. The "Ljubljana implant" was developed through experiments on animals and later with two volunteers. It has a typical electrode configuration, acceptable miniaturization and reduces the amount of surgery necessary. This system was tested in 14 patients, primarily as a part of an implantable peroneal brace. For five years the system has been reliable and safe. It may be possible to apply this implant as part of a multi-channel control system.


Comparative performance of electrospun collagen nanofibers cross-linked by means of different methods.
Collagen, as the major structural protein of the extracellular matrix in animals, is a versatile biomaterial of great interest in various engineering applications. Electrospun nanofibers of collagen are regarded as very promising materials for tissue engineering applications because they can reproduce the morphology of the natural bone but have as a drawback a poor structural consistency in wet conditions. In this paper, a comparative study between the performance of different cross-linking methods such as a milder enzymatic treatment procedure using transglutaminase, the use of N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide, and genipin, and the use of a physical method based on exposure to ultraviolet light was carried out. The chemical and enzymatic treatments provided, in this order, excellent consistency, morphology, cross-linking degree, and osteoblast viability for the collagen nanofibers. Interestingly, the enzymatically cross-linked collagen mats, which are considered to be a more biological treatment, promoted adequate cell adhesion, making the biomaterial biocompatible and with an adequate degree of porosity for cell seeding and in-growth.


Determination of four active saponins of Panax notoginseng in rat feces by high-performance liquid chromatography.
A method is developed for the determination of ginsenoside Rg1, Rb1, Rd, and notoginsenoside R1 of Panax notoginseng (PNS) in rat feces after oral and intravenous administration of total saponins of PNS. The fecal samples are treated with organic extraction and solid-phase extraction prior to high-performance liquid chromatography. The calibration curves for the four saponins are linear in the given concentration ranges. The precision of the method is in the range of 1.0-10.0% (relative standard deviation), and the accuracy is between 80.0% and 110%. The recoveries of this method are all over 75%. This method is successfully applied to the analyses of fecal samples of rats treated with PNS.


Simulation study on kinetic temperatures of vibrated binary granular mixtures.
We study the unequal kinetic temperatures in two-dimensional binary granular mixtures heated by vertical vibrations under gravity by molecular dynamics simulations. By introducing several variable parameters describing particle and composition properties of mixtures, the coexistence of two different kinetic temperatures for the two components is exhibited. In dilute situations, our numerical results confirm the overall experimental measurements by Feitosa and Menon recently [Phys. Rev. Lett. 88, 198301 (2002)]. For example, the temperature ratio along the vertical direction is constant in the bulk of a system, and is insensitive to external driving or relative concentration of the two components, but mainly influenced by their masses. However, outside of the dilute situations, especially as the number density becomes high enough where the spatial and momentum correlations become salient, the ratio profiles show some different characteristics. Generally, the plateau shape along the vertical direction is broken, and instead, a saddlelike shape appears. Furthermore, the physical implications are discussed.


The frequency of double-positive thymocytes expressing an alphabeta TCR clonotype regulates peripheral CD4 T cell compartment homeostasis.
The present study aimed to determine whether the frequency of double positive (DP) thymocytes expressing alphabeta T-cell receptor (TCR) clonotypes at the time of selection regulates peripheral CD4 T-cell compartment size. Scid recipients were inoculated with various ratios of TCR Calpha(0/0) and wild-type bone marrow (BM) stem cells. Increasing the frequency of TCR Calpha(0/0) thymocytes at steady-state introduced a graded decrease in the maturation probability of the total DP thymocyte pool. At 12-14 weeks following BM inoculation, the frequency of TCR Calpha(0/0) DP thymocytes was inversely correlated with that of CD4 single positive (SP) thymocytes. Notwithstanding, a decreased frequency of wild-type DP thymocytes led to a marked increase in their transit efficiency from the DP to SP compartments. The frequency-dependent increase in thymocyte transit efficiency was associated with a CD4 SP cell surface phenotype indicative of increased antigenic experience. Importantly, the frequency of DP thymocytes capable of expressing TCR clonotypes dictated the steady-state size of the peripheral CD4 T cell compartment and its potential for homeostatic proliferation. Collectively, these results indicate that the efficiency of DP to CD4 SP transit is a frequency dependent process, which determines (1) the steady-state size of the peripheral T cell compartment and (2) the threshold for homeostatic expansion of peripheral CD4 T cells.


Reversal of cholecystokinin-induced persistent stimulation of pancreatic enzyme secretion by dibutyryl cyclic GMP.
When pancreatic acini are first incubated with cholecystokinin, washed to remove free cholecystokinin, and then reincubated in fresh incubation solution, there is a significant residual stimulation of amylase secretion. Butyryl derivatives of cyclic GMP can prevent as well as reverse this cholecystokinin-induced residual stimulation. At 37 degrees C the nucleotide-induced reversal is complete within a few minutes, but at 4 degrees C complete reversal requires 90 min of incubation. The ability of butyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation is itself fully reversible, and the nucleotide-induced reversal is accompanied by restoration of full responsiveness to cholecystokinin. The ability of dibutyryl cyclic GMP to reverse cholecystokinin-induced residual stimulation appears to result from the ability of the nucleotide to displace cholecystokinin from its receptors in pancreatic acini.


Effect of semen extenders on viability of ISA Brown and Hubbard Flex roosters' sperm stored for 24 h.
Artificial insemination is used in almost 95% of turkey reproductive flocks and is becoming more important in chickens, particularly broiler breeders, as well as in assisted reproduction of wild birds kept in breeding centers. Diluted semen is recommended for artificial insemination. Pooled semen samples collected twice a week by dorso-abdominal massage from 2 chicken lines: laying-ISA Brown (ISA-B) and meat type-Hubbard Flex (H-F) were divided into 5 parts: neat semen and diluted in 1:2 ratio with 4 extenders: basic EK; EK + 1 μg/mL organic selenium and 8 μg/mL vitamin E; EK + 10 mg/mL of royal jelly; and EK + 0.25 g/mL of lyophilized bovine colostrum. Diluted semen samples were evaluated after 15 min and then 24 h storage at 4°C. Sperm concentration, motility, motility parameters (with Sperm Class Analyzer), and morphology were evaluated in the neat semen, whereas in diluted and stored samples, the last 3 traits were determined. In case of both lines, dilution did not affect (P > 0.05) the number of live normal cells (78.0-81.1% in ISA Brown and 73.8-68.7% in Hubbard Flex) in relation to neat semen; however, bovine colostrum addition increased (P < 0.05) the percentage of bulb head sperm (5.7 vs. 10.0% and 12.1 vs. 17.6%, for ISA and Hubbard, respectively) and decreased sperm motility (67.4 vs. 92.9% and 67.3 vs. 98.5% for ISA and Hubbard). The 24 h storage of neat semen and semen diluted with colostrum caused (P < 0.05) the unfavorable changes in all evaluated traits and both chicken lines, whereas semen dilution with remaining extenders decreased the percentage of live normal cells (by 18.8-23.4% ISA and by 20.9-25.5% Hubbard) but did not affect sperm motility (81.5-87.6% for ISA and 81.1-96.6% for Hubbard). Sperm motility and motility parameters depended both on the extender and chicken line.


Oviposition of Aedes aegypti and Aedes albopictus on Ovitraps in Dry and Rainy Seasons in Southern Vietnam.
Ovitraps were set inside and outside of 15 households in December 2012 (dry season) and August 2013 (rainy season) in 2 communes (An Thanh and Phu Hoa) of Binh Duong Province in southern Vietnam. Eggs laid in the ovitraps were collected after 4 days, dried, and soaked in water. Hatched larvae were transferred to cups and reared to adulthood to identify the species. The rate of positive ovitraps did not differ between December and August for Aedes aegypti, but it was lower in December for Ae. albopictus. The number of eggs laid per ovitrap by Ae. aegypti did not differ between December and August, while that for Ae. albopictus decreased significantly in December in both communes. Moreover, Ae. albopictus laid eggs in ovitraps placed outside the households. Therefore, it is necessary for future studies to investigate whether the major source containers for oviposition had dried in the dry season or Ae. albopictus entered diapause, leading to these observations.


Synthesis of novel DOTA-/AAZTA-based bifunctional chelators: Solution thermodynamics, peptidomimetic conjugation, and radiopharmaceutical evaluation.
Bifunctional chelators (BFCs), which link metallic radionuclide and a targeting vector, are some of the most crucial components of metallic radionuclide-based radiopharmaceuticals for positron-emission computed tomography (PET) imaging. In this study, we designed and synthesized two versatile BFCs, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA, and we conjugated them with a prostate-specific membrane antigen (PSMA) inhibitor. These two chelators showed high affinity for Ga (III) according to a study of the thermodynamics and kinetics and DFT calculations. The labeled PSMA targeted probes, [68Ga]Ga-p-NCS-Ph-DE4TA-PSMA and [68Ga]Ga-p-NCS-Ph-AAZ4TA-PSMA, maintained excellent stability in vitro, and they exhibited high specific activity when binding to PSMA. A PET/CT imaging study in mice bearing SMMC-7721 hepatocellular carcinoma xenografts demonstrated clear visualization of tumors with a high tumor uptake and low background level, indicating the excellent performance in vivo and specific activity when targeting hepatocellular carcinomas. In summary, p-NCS-Ph-DE4TA and p-NCS-Ph-AAZ4TA are leading developmental candidates for PET imaging for tumor diagnosis.


Pilot and Feasibility of Combining a Medication Adherence Intervention and Group Diabetes Education for Patients with Type-2 Diabetes.
Introduction: Controlling diabetes typically requires self-management and medications. Community pharmacists are positioned to support patients with both. Methods: This study assessed the feasibility and potential benefit of combining pharmacist-provided group diabetes education (up to eight sessions) and medication synchronization using a three-group design. Data were collected using pre-post paper surveys and electronic health record data. One group received both education and synchronization services, another group received medication synchronization only, and a third served as control. Results: Of 300 contacted patients, eighteen patients participated in group diabetes education, 14 had medication synchronization only, and 12 comprised a control group. There was little change in HbA1c over the study period. Medication adherence appeared to be positively aided by medication synchronization, although all groups started with high adherence. Some medication beliefs and self-care activities may have been positively impacted by group diabetes education. Both groups receiving medication synchronization were satisfied. Conclusions: Participants strongly agreed they would recommend group diabetes education from the study pharmacy to a friend and were satisfied with medication synchronization; however, it was difficult to tell if there was a synergistic effect by combining the two services. Reimbursement for diabetes education was not obtained despite multiple attempts, hindering sustainability.


Urinary cytodiagnosis of renal involvement in disseminated histiocytic lymphoma.
Two cases of patients with disseminated histiocytic lymphoma are presented in which positive urine cytology provided evidence of renal involvement. In addition to malignant cells, the urine sediment characteristics included renal tubular epithelial cell exfoliation, renal epithelial fragments and pathologic cast formation, which distinguished renal from lower urinary tract involvement. Such cytologic observations may be useful in differentiating among the various causes of renal disease in patients with malignant lymphomas.


Protective Immunity Induced by Incorporating Multiple Antigenic Proteins of Toxoplasma gondii Into Influenza Virus-Like Particles.
Virus-like particle (VLP) as a highly efficient vaccine platform has been used to present single or multiple antigenic proteins. In this study, we generated VLPs (multi-antigen VLPs, TG146) in insect cells co-infected with recombinant baculoviruses presenting IMC, ROP18, and MIC8 of Toxoplasma gondii together with influenza matrix protein 1 (M1) as a core protein. We also generated three VLPs expressing IMC, ROP18, or MIC8 together with M1 for combination VLPs (TG1/TG4/TG6). A total of four kinds of VLPs generated were characterized by TEM. Higher number of VLPs particles per μm2 were observed in multi-antigen VLPs compared to combination VLPs. Mice (BALB/c) were intranasually immunized with multi-antigen VLPs or combination VLPs and challenged with T. gondii tachyzoites (GT1) intraperitoneally. Compared to combination VLPs, multi-antigen VLPs showed significantly higher levels of CD4+ T cell, and germinal center B cell responses with reduced apoptosis responses, resulting in significant reduction on parasite burden. These results indicate that higher efficacy of VLPs generated by multi-antigen VLPs can induce significant reduction of parasite burden and better survival of mice than that by combination VLPs, providing important insights into vaccine design strategy for VLPs vaccine expressing multiple antigenic proteins.


Aromatic Plants as Potential Resources to Combat Osteoarthritis.
Osteoarthritis, which affects an estimated 10% of men and 18% of women over the age of 60 and is increasing in genetic prevalence and incidence, is acknowledged as the condition that degrades the quality of life for older adults in the world. There is currently no known treatment for osteoarthritis. The majority of therapeutic methods slow the progression of arthritis or treat its symptoms, making effective treatment to end the degenerative process of arthritis elusive. When non-pharmacological therapy is ineffective, various pharmacological therapies may be used to treat osteoarthritis. Pharmacological therapy, however, can have major adverse effects and be very expensive. As a result, alternative remedies have been researched. The promise for the safe and efficient management of osteoarthritis has been demonstrated by herbal remedies. Experimental research suggests that herbal extracts and compounds can reduce inflammation, inhibit catabolic processes, and promote anabolic processes that are important for treating osteoarthritis. Due to their therapeutic and innate pharmacological qualities, aromatic herbs are frequently employed as herbal remedies. Recent research has shown that aromatic plants have the potency to treat osteoarthritis. Additionally, complex mixtures of essential oils and their bioactive ingredients, which have anti-inflammatory and antioxidant properties and are obtained from aromatic plants, are frequently utilized as complementary therapies for osteoarthritis. To establish new study avenues, the advantageous anti-osteoarthritic effects of aromatic herbal medicines, including plants, essential oils, and their bioactive components, are extensively discussed.


Degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) using zerovalent iron nanoparticles.
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a common contaminant of soil and water at military facilities. The present study describes degradation of RDX with zerovalent iron nanoparticles (ZVINs) in water in the presence or absence of a stabilizer additive such as carboxymethyl cellulose (CMC) or poly(acrylic acid) (PAA). The rates of RDX degradation in solution followed this order CMC-ZVINs > PAA-ZVINs > ZVINs with k1 values of 0.816 +/- 0.067, 0.082 +/- 0.002, and 0.019 +/- 0.002 min(-1), respectively. The disappearance of RDX was accompanied by the formation of formaldehyde, nitrogen, nitrite, ammonium, nitrous oxide, and hydrazine by the intermediary formation of methylenedinitramine (MEDINA), MNX (hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine), DNX (hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine), TNX (hexahydro-1,3,5-trinitroso-1,3,5-triazine). When either of the reduced RDX products (MNX or TNX) was treated with ZVINs we observed nitrite (from MNX only), NO (from TNX only), N2O, NH4+, NH2NH2 and HCHO. In the case of TNX we observed a new key product that we tentatively identified as 1,3-dinitroso-5-hydro-1,3,5-triazacyclo-hexane. However, we were unable to detect the equivalent denitrohydrogenated product of RDX and MNX degradation. Finally, during MNX degradation we detected a new intermediate identified as N-nitroso-methylenenitramine (ONNHCH2NHNO2), the equivalentof methylenedinitramine formed upon denitration of RDX. Experimental evidence gathered thus far suggested that ZVINs degraded RDX and MNX via initial denitration and sequential reduction to the corresponding nitroso derivatives prior to completed decomposition but degraded TNX exclusively via initial cleavage of the N-NO bond(s).


[CYSTECTASY AND REHABILITATION TRAINING FOR TREATMENT OF NEUROGENIC BLADDER DYSFUNCTION WITH HYPERREFLEXIA].
To investigate the effectiveness of ileal mucosal seromuscular patch for bladder expansion combined with rehabilitation training for treating neurogenic bladder dysfunction (NBD) with hyperreflexia. A retrospective study was performed on the clinical data of 61 patients with NBD and hyperreflexia who were treated and followed up between July 2008 and June 2013. There were 36 males and 25 females, aged 6-23 years (mean, 10 years). The reasons included meningomyelocele operation (43 patients),surgery for lipoma in lumbar vertebra (4 patients), operation of thoracolubar teratoma (2 patients), and lumbosacral spina B3ifida (12 patients). The results of urodynamics indicated that bladder volume decreased obviously and the residual urine increased. The voiding cystourethrography (VCUG) showed the vesicoureteral reflux (VUR), including 6 cases (10 sides) of grade V, 7 cases (12 sides) of grade IV, and 6 cases (8 sides) of grade III. The color doppler ultrosound showed mild hydronephrosis in 23 cases (41 sides), moderate hydronephrosis in 25 cases (42 sides), and severe hydronephrosis in 13 cases (22 sides). The blood biochemical examination suggested chronic renal failure (CRF) in 13 cases. The treatment included augmentation for bladder and rehabilitation training after operation. The operation time was (157+/- 26) minutes; the intraoperative blood loss was (43 +/- 15) mL, and no patient was given blood transfusion. The patients were followed up 1.5-6.0 years (mean, 4.5 years). Vesical fistula occurred in 4 cases, urinary infection in 5 cases, dysuresia in 2 cases, and cystolith in 1 case after operation. At 1 year after operation, the International Consultation on Incontinence Questionnaire-Urinary Incontience Short Form (IQ-F) score was significantly better than peoperative score (H=9.813, P=0.000). The aurdynmic data showed that the difference value between observed and theoretical bladder volumes, bladder compliance, residual urine volume, maximum flow rate, and maximum storage detrusor pressure were significantly better than preoperative ones (P<0.05). And the color doppler ultrasound showed mild hydronephrosis in 34 cases (56 sides), moderate hydronephrosis in 18 cases (33 sides), and severe hydronephrosis in 9 cases (16 sides). VCUG showed that bladder volume obviously increased, no contracture was observed; and VUR was improved. And renal function was improved in 13 patients with CRF. Heal mucosal seromuscular patch for bladder expansion combined with postoperative rehabilitation training has good effectiveness in treating NBD with hyperreflexia.


Interface Engineering for Garnet-Based Solid-State Lithium-Metal Batteries: Materials, Structures, and Characterization.
Lithium-metal batteries are considered one of the most promising energy-storage systems owing to their high energy density, but their practical applications have long been hindered by significant safety concerns and poor cycle stability. Solid-state electrolytes (SSEs) are expected to improve not only the safety but also the energy density of Li-metal batteries. The key challenge for solid-state Li-metal batteries lies in the low ionic conductivity of the SSEs and moreover the interface contact between the electrode and SSE. To achieve feasible solid-state Li-metal batteries, it is imperative that the ionic conductivity is improved, especially at the electrode-SSE interface. Herein, recent advances in interface engineering for solid-state Li-metal batteries are reported, mainly focusing on garnet-type SSEs. Various materials to modify the cathode-garnet and Li-garnet interfaces by intermediate layers, alloys, and polymer electrolytes are analyzed. Structural innovations for SSEs including composite electrolytes and multilayer SSE frameworks are reviewed, along with advanced characterization approaches to probe the interfaces, which will provide further insights for garnet-based solid-state batteries. Future challenges and the great promise of garnet-based Li-metal batteries are discussed to close.


A comparison of the video head impulse test and the functional head impulse test in chronic unilateral vestibular loss.
To examine the correlation of video head impulse test, functional head impulse test and Dizziness Handicap Inventory results in patients with chronic unilateral vestibular loss, and to compare the results with healthy controls. Forty-eight patients diagnosed with chronic unilateral vestibular loss and 35 healthy individuals, aged 18-65 years, were included. The video head impulse test, functional head impulse test and Dizziness Handicap Inventory were administered. A significant positive correlation was found between functional head impulse test and video head impulse test results for the study group in all semicircular canals (p < 0.05). There was no significant correlation between Dizziness Handicap Inventory, functional head impulse test and video head impulse test results (p > 0.05). The functional head impulse test and video head impulse test results of the control group were significantly higher than those of the study group in all semicircular canals planes (p < 0.05). In chronic unilateral vestibular loss patients, with high head accelerations, the functional head impulse test indicates deterioration in vestibulo-ocular reflex functionality. It would be beneficial to include the video head impulse test and functional head impulse test in clinical practice as complementary tests in vestibulo-ocular reflex evaluation.


Medial temporal lobe and topographical memory.
There has been interest in the idea that medial temporal lobe (MTL) structures might be especially important for spatial processing and spatial memory. We tested the proposal that the MTL has a specific role in topographical memory as assessed in tasks of scene memory where the viewpoint shifts from study to test. Building on materials used previously for such studies, we administered three different tasks in a total of nine conditions. Participants studied a scene depicting four hills of different shapes and sizes and made a choice among four test images. In the Rotation task, the correct choice depicted the study scene from a shifted perspective. MTL patients succeeded when the study and test images were presented together but failed the moment the study scene was removed (even at a 0-s delay). In the No-Rotation task, the correct choice was a duplicate of the study scene. Patients were impaired to the same extent in the No-Rotation and Rotation tasks after matching for difficulty. Thus, an inability to accommodate changes in viewpoint does not account for patient impairment. In the Nonspatial-Perceptual task, the correct choice depicted the same overall coloring as the study scene. Patients were intact at a 2-s delay but failed at longer, distraction-filled delays. The different results for the spatial and nonspatial tasks are discussed in terms of differences in demand on working memory. We suggest that the difficulty of the spatial tasks rests on the neocortex and on the limitations of working memory, not on the MTL.


A Robust Metabolic Enzyme-Based Prognostic Signature for Head and Neck Squamous Cell Carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known. Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated. A total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells. Our study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. Moreover, the nomogram model might provide useful guidance for the precision treatment of HNSCC.


Sex differences in muscle protein expression and DNA methylation in response to exercise training.
Exercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood. We performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption; VO2max) in a sex-specific manner. Here, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes. We identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.


Report of the AMA Board of Trustees.
Single-payer proposals that promise to provide universal coverage, maintain fee-for-service medicine, protect physician autonomy, restrain health spending, and simplify reimbursement and billing may appear enticing. However, the Board of Trustees continues to find that single-payer systems with strict global budgets: fail to provide adequate and timely urgent and elective specialty services; continue to encroach on physician autonomy and the physician-patient relationship; neglect changes in technology; have not been able to stabilize health spending; and incur some of the same administrative costs as multiple-payer systems. References for this report are available upon request.


Effects of tibolone on bone quality in ovariectomized monkeys.
The purpose of this report is to examine the effects of two doses of tibolone on bone quality (bone biomarkers, bone density, and bone strength) in ovariectomized cynomolgus monkeys fed high-fat diets. Ovariectomized cynomolgus monkeys were randomized into one of five treatment groups: placebo-treated control, tibolone (0.2 mg/kg/day), tibolone (0.05 mg/kg/day), conjugated equine estrogens (Premarin, 0.042 mg/kg/day), and conjugated equine estrogens plus medroxyprogesterone acetate (0.042 and 0.167 mg/kg/day, respectively). Bone quality was assessed by determining bone strength and density in vertebrae and femora collected after 24 months of treatment. Monkeys treated for 24 months with tibolone had increased bone mineral density in the distal femur and improved biomechanical properties in the midshaft femur compared with placebo-treated ovariectomized monkeys, as did monkeys treated with conjugated equine estrogens with or without medroxyprogesterone acetate. No treatment effects were seen in lumbar vertebra bone density or strength. There was no significant difference between tibolone and estrogen on biomechanical properties of the femur. These data show that tibolone is comparable to conjugated equine estrogens with or without medroxyprogesterone acetate in decreasing bone turnover and increasing bone strength in ovariectomized monkeys.


Intrafamilial correlation analysis for IgM serum levels.
The IgM serum level was determined in the members of 29 healthy families. The IgM mean concentrations between fathers and mothers and between sons and daughters were significantly different (P less than .01), with higher serum IgM levels in females than in males. Simple linear regression analysis was done for the following intrafamilial combinations: son-father, daughter-father, son-mother, and daughter-mother. Significant correlation coefficients (P less than .05) were obtained in all four combinations, which does not support the X-linked gene hypothesis (i.e., that the X chromosome carries quantitative genes for immunoglobulin M). An alternative explanation for the differences between sexes for IgM serum concentration is considered.


Possible neural network mediating jaw opening during prey-catching behavior of the frog.
The prey-catching behavior of the frog is a complex, well-timed sequence of stimulus response chain of movements. After visual analysis of the prey, a size dependent program is selected in the motor pattern generator of the brainstem. Besides this predetermined feeding program, various direct and indirect sensory inputs provide flexible adjustment for the optimal contraction of the executive muscles. The aim of the present study was to investigate whether trigeminal primary afferents establish direct contacts with the jaw opening motoneurons innervated by the facial nerve. The experiments were carried out on Rana esculenta (Pelophylax esculentus), where the trigeminal and facial nerves were labeled simultaneously with different fluorescent dyes. Using a confocal laser scanning microscope, close appositions were detected between trigeminal afferent fibers and somatodendritic components of the facial motoneurons. Quantitative analysis revealed that the majority of close contacts were encountered on the dendrites of facial motoneurons and approximately 10% of them were located on the perikarya. We suggest that the identified contacts between the trigeminal afferents and facial motoneurons presented here may be one of the morphological substrate in the feedback and feedforward modulation of the rapidly changing activity of the jaw opening muscle during the prey-catching behavior.


Semiautomatic High-Content Analysis of Complex Images from Cocultures of Vascular Smooth Muscle Cells and Macrophages: A CellProfiler Showcase.
Automatization in microscopy, cell culture, and the ease of digital imagery allow obtainment of more information from single samples and upscaling of image-based analysis to high-content approaches. Simple segmentation algorithms of biological imagery are nowadays widely spread in biomedical research, but processing of complex sample structures, for example, variable sample compositions, cell shapes, and sizes, and rare events remains a difficult task. As there is no perfect method for image segmentation and fully automatic image analysis of complex content, we aimed to succeed by identification of unique and reliable features within the sample. Through exemplary use of a coculture of vascular smooth muscle cells (VSMCs) and macrophages (MPs), we demonstrate how rare interactions within this highly variable sample type can be analyzed. Because of limitations in immunocytochemistry in our specific setup, we developed a semiautomatic approach to examine the interaction of lipid-laden MPs with VSMCs under hypoxic conditions based on nuclei morphology by high-content analysis using the open-source software CellProfiler ( www.cellprofiler.org ). We provide evidence that, in comparison with fully automatic analysis, a low threshold within the analysis workflow and subsequent manual control save time, while providing more objective and reliable results.


The effectiveness of a psycho-educational group after early-stage breast cancer treatment: results of a randomized French study.
Many women with breast cancer need psychological help to cope more effectively after treatment. Cognitive and behavioural techniques are not yet well established in France. A multi-site randomized study was conducted to evaluate the effects of a psycho-educational group intervention in this population. Two hundred and three patients, recruited after primary treatment, were randomly assigned either to a treatment group (psycho-educational intervention) or to a waiting-list control group. The 8-week programme of 2 h sessions comprised of thematic discussions, information and training in stress management techniques. Evaluation at baseline, after 8 sessions, and 1 month after programme completion, included evaluations using the STAI, POMS, MAC, EORTC QLQ-C30 and EORTC QLQ-BR23 breast module scales. We observed a significant reduction in anxiety (STAI, POMS) among group participants, a reduction in anger, depression and fatigue (POMS), a significant improvement in vigor and interpersonal relationships (POMS), in emotional and role functioning, in health status and fatigue level (EORTC QLQ-C30). In contrast, coping strategies (MAC) were not significantly different between groups. No group-related negative effects were observed and the global satisfaction levels were very high. This study demonstrates the feasibility and effectiveness of a psycho-educational intervention, which can accelerate the reduction of those negative affects which are present at the end of treatment. It represents an excellent complement or an alternative to individual psycho-oncologic therapeutic support, widely proposed in France, and should now be tested in groups with other types of cancer and at other disease phases.


An education programme for people with cancer.
Evidence suggests that cancer patients want support, information and to be involved in treatment decisions. A course designed in the USA aims to help cancer patients learn more about the disease and become an informed part of the therapeutic team. The introduction of a similar course at one UK centre suggested that it is an effective way of informing and supporting people.


Analysis of the miRNA-mRNA networks in malignant transformation BEAS-2B cells induced by alpha-particles.
The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA. Bioinformatic software was used to analyze these different mRNA and miRNA, which indicated that miR-107 and miR-494 play an important role in alpha-particles-mediated cellular malignant transformation processes. The pathways related to systemic lupus erythematosus, cytokine-cytokine receptor interaction, MAPK signaling pathway, regulation of actin cytoskeleton, and cell adhesion molecules (CAMs) were stimulated, while those of ribosome, transforming growth factor (TGF)-beta signaling pathway, and metabolic pathways were inhibited. Data suggest that miRNA and mRNA play a crucial role in alpha-particles-mediated malignant transformation processes. It is worth noting that three target genes associated with lung cancer were identified and upregulated PEG 10 (paternally expressed gene 10), ARHGAP26, and IRS1.


Phosphorylation in vitro of the large subunit of the ribulose-1,5-bisphosphate carboxylase and of the glyceraldehyde-3-phosphate dehydrogenase.
A protein kinase activity responsible for the in vitro phosphorylation of at least six endogenous polypeptides including the large subunit of the ribulose-1,5-bisphosphate carboxylase/oxygenase (EC 18.104.22.168) is present in the stroma (3000 X g supernatant, S30) of spinach chloroplasts. The phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is strongly enhanced when sodium fluorure is used as a protein phosphatase inhibitor. Phosphorylation occurs on threonine and serine residues. The protein kinase involved is not Ca2+-dependent. There is also evidence for a protein phosphatase activity which suggests a coupled regulation by a phosphorylation-dephosphorylation process. The phosphorylating activity is drastically reduced when S30 is prepared from leaves harvested after a dark period. Phosphorylation of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit is not related to its own synthesis. The in vitro phosphorylation of the glyceraldehyde-3-phosphate dehydrogenase (EC 22.214.171.124) is also demonstrated.


Si/Ge interfacial thermal conductance enhancement through Sn nanoparticle embedding.
The improvement of interfacial thermal conductance (ITC) is a crucial aspect of the thermal management of nanodevices. In this paper, the effect of embedding Sn nanoparticles at the Si/Ge interface on ITC was investigated using non-equilibrium molecular dynamics (NEMD) simulations. It was found that although Sn has a higher atomic weight than both silicon and germanium, the ITC can be enhanced by 1.95 times when the nanoparticles reach a suitable number and diameter. The phonon transmission functions and density of states clearly indicate that an increased ITC can be attributed to the enhanced inelastic phonon scattering facilitated by Sn nanoparticles. This enhancement opens up novel channels for interfacial phonon transport. However, when the number of nanoparticles surpasses a suitable value, elastic phonons begin to dominate heat transport, leading to a subsequent decrease in the ITC. Sensitivity analysis further underscores that the ITC exhibits greater responsiveness to changes in diameter. In addition, it is also shown that with increasing temperature, a higher frequency phonon excitation occurs, increasing phonon inelastic scattering and interface transmission. These findings offer a novel strategy for enhancing ITC and deepening our comprehension of both elastic and inelastic phonon processes in interfacial phonon transport.


Mechanism of immunotherapeutic activity of OK-432 in the treatment of peritoneal carcinomatosis.
In this report the mechanism of therapeutic activity of OK-432 for the treatment of peritoneal carcinomatosis was investigated by correlating effector-cell augmentation with therapeutic activity in rats bearing MADB-106 carcinomatosis. Tumor cells were injected i.p. and the treatment with OK-432 was initiated 5 days later with 0.5, 1, 5 or 10 KE/animal of OK-432 injected i.p. semiweekly. Significant therapeutic activity was observed at all doses examined with greater prolongation of survival noted at the higher doses of OK-432. Animals treated with 0.5 KE/animal had a prolongation of the median survival time from 14 days for saline-treated animals to 17 days for the OK-432 treated animals (P less than 0.0008), while animals treated with higher doses had much longer periods of survival, some animals being tumor-free at 185 days. In the same studies, natural killer (NK) cell, lymphokine-activated killer cell, cytotoxic T lymphocyte, and macrophage tumoricidal/cytostatic activities were measured 7 days and 14 days following tumor injection (2 days and 9 days after initiation of immunotherapy). OK-432 had immunostimulatory activity in most of the assays of immune function examined and this correlated with host survival, including augmentation of peritoneal and peripheral blood cytotoxic T lymphocyte activity on day 14, peritoneal and alveolar macrophage activity on day 7 and day 14, as well as natural killer cell activity on day 14. These results suggest that the therapeutic doses are also immunomodulatory doses for the effector cells mentioned above. We suggest, therefore, that immunological monitoring may help to optimize treatment protocols for the treatment of peritoneal and perhaps pleural effusions with OK-432.


In vitro degradation and fracture toughness of multilayered porous poly(propylene fumarate)/beta-tricalcium phosphate scaffolds.
This study investigated the in vitro degradation of poly(propylene fumarate)/beta-tricalcium phosphate (PPF/beta-TCP) scaffolds in pH 7.4 phosphate-buffered saline at 37 degrees C. Scaffold design consisted of three layers: two solid layers about a central layer of porous PPF foam. Solid PPF with molecular weights of 810 and 1450 Da was crosslinked under UV light. PPF foam was prepared by a photocrosslinking, porogen-leaching method with an initial porogen content of 80 wt % and two sizes, 150-300 and 300-500 microm. Comparison of initial and residual weights demonstrated a 14.3 +/- 2.0% loss of mass at 3 weeks and a 16.6 +/- 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained stable (7.15-7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of these scaffolds revealed some loss of foam material between 3 and 6 weeks; however, foam microarchitecture was intact. Solid PPF fracture toughness was tested for high and low molecular weight PPF, 0.376 +/- 0.004 and 0.134 +/- 0.015 MPa(m)1/2, respectively. These values are roughly one magnitude less than human cortical bone.


Upregulation of Wnt signaling under hypoxia promotes lung cancer progression.
The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus. Overexpression of HIF-2α increased β-catenin expression, promoted cell mobility, and induced morphological changes to a greater degree than HIF-1α overexpression. Knockdown of HIF-2α decreased β-catenin expression and inhibited hypoxia-induced cell mobility. Moreover, we identified that phosphorylational activation of AKT1 by hypoxia and HIF-2α was required for Wnt activation upon hypoxia treatment. Downregulation of HIF-2α and β-catenin reduced colony formation when cells were exposed to long-term hypoxia treatment. Taken together, our data support that hypoxia activates PI3K/AKT as well as Wnt signaling in a HIF-2α-dependent manner, thus elevating the resistance of lung cancer cells to chronic hypoxia-induced stress.


Cortex Parcellation Associated Whole White Matter Parcellation in Individual Subjects.
The investigation of specific white matter areas is a growing field in neurological research and is typically achieved through the use of atlases. However, the definition of anatomically based regions remains challenging for the white matter and thus hinders region-specific analysis in individual subjects. In this article, we focus on creating a whole white matter parcellation method for individual subjects where these areas can be associated to cortex regions. This is done by combining cortex parcellation and fiber tracking data. By tracking fibers out of each cortex region and labeling the fibers according to their origin, we populate a candidate image. We then derive the white matter parcellation by classifying each white matter voxel according to the distribution of labels in the corresponding voxel from the candidate image. The parcellation of the white matter with the presented method is highly reliable and is not as dependent on registration as with white matter atlases. This method allows for the parcellation of the whole white matter into individual cortex region associated areas and, therefore, associates white matter alterations to cortex regions. In addition, we compare the results from the presented method to existing atlases. The areas generated by the presented method are not as sharply defined as the areas in most existing atlases; however, they are computed directly in the DWI space of the subject and, therefore, do not suffer from distortion caused by registration. The presented approach might be a promising tool for clinical and basic research to investigate modalities or system specific micro structural alterations of white matter areas in a quantitative manner.


In vitro organogenesis and alkaloid accumulation in Datura innoxia.
The kinetics of tropane alkaloids accumulation in different organs such as roots, leaves, stems, flowers and seeds of Datura innoxia was investigated by GC-MS. Twenty-six tropane alkaloids were detected. The ester derivatives of tropine (3alpha-tigloyloxytropine and 3-tigloyloxy-6-hydroxytropine) are the major compounds. Undifferentiated callus were established from the stem explants of Datura innoxia using Murashige and Skoog (MS) medium supplied with 6-benzylaminopurine (BA, 1 mg l(-10) and indole-3-acetic acid (IAA, 0.5 mg l(-1)) in combination for 6 weeks. Callus differentiation was initiated by subculture onto solid MS medium, free from hormones, for more than 10 months. Initially, shoots were formed after four weeks from subculture. Further subculturing in basal MS medium without growth regulators initiated the rooting of a shooty callus after 6 weeks. Investigation of the alkaloid content of the unorganized and organized callus revealed that callus (either green or brown) yielded only trace amounts of alkaloids. On the other hand, re-differentiated shoots contained mainly scopolamine while re-differentiated roots biosynthesized hyoscyamine as the main alkaloid.


Predicting variant deleteriousness in non-human species: applying the CADD approach in mouse.
Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less data for non-human species. Here, we investigate the prerequisites to construct a CADD-based model for a non-human species. Performance of the mouse model is competitive with that of the human CADD model and better than established methods like PhastCons conservation scores and SIFT. Like in the human case, performance varies for different genomic regions and is best for coding regions. We also show the benefits of generating a species-specific model over lifting variants to a different species or applying a generic model. With fewer genomic annotations, performance on the test set as well as on the three validation sets is still good. It is feasible to construct species-specific CADD models even when annotations such as epigenetic markers are not available. The minimal requirement for these models is the availability of a set of genomes of closely related species that can be used to infer an ancestor genome and substitution rates for the data generation.


TRIM69 suppressed the anoikis resistance and metastasis of gastric cancer through ubiquitin‒proteasome-mediated degradation of PRKCD.
The tripartite motif (TRIM) protein family has been investigated in multiple human cancers, including gastric cancer (GC). However, the role of TRIM69 in the anoikis resistance and metastasis of GC cells remains to be elucidated. We identified the differentially expressed genes in anoikis-resistant GC cells using RNA-sequencing analysis. The interaction between TRIM69 and PRKCD was analyzed by coimmunoprecipitation and mass spectrometry. Our results have shown that TRIM69 was significantly downregulated in anoikis-resistant GC cells. TRIM69 overexpression markedly suppressed the anoikis resistance and metastasis of GC cells in vitro and in vivo. TRIM69 knockdown had the opposite effects. Mechanistically, TRIM69 interacted with PRKCD through its B-box domain and catalyzed the K48-linked polyubiquitination of PRKCD. Moreover, TRIM69 inhibited BDNF production in a PRKCD-dependent manner. Importantly, overexpression of PRKCD or BDNF blocked the effects of TRIM69 on the anoikis resistance and metastasis of GC cells. Interestingly, a TRIM69-PRKCD+BDNF+ cell subset was positively associated with metastasis in GC patients. TRIM69-mediated suppression of the anoikis resistance and metastasis of GC cells via modulation of the PRKCD/BDNF axis, with potential implications for novel therapeutic approaches for metastatic GC.


Novel copy number variation of the TGFβ3 gene is associated with TGFβ3 gene expression and duration of fertility traits in hens.
Improvements in the duration of fertility (DF) could increase the interval between successive artificial inseminations, thereby decreasing the cost associated with production of hatching eggs. The molecular mechanisms involved in DF in hens remains under-explored. In this study, expression levels of the transforming growth factor-β genes (TGFβs: TGFβ1, TGFβ2, TGFβ3) were investigated in utero-vaginal junctions (UVJs) of hens with long DF (Group L, n = 10) and short DF (Group S, n = 10). TGFβ1 and 2 tended to exhibit higher expression levels in UVJs from Group L hens. The expression levels of TGFβ3 mRNA and protein were significantly increased in UVJs of hens from Group L compared to hens in Group S. Consistently, six TGFβs downstream genes (DAXX, MEKK1, T-BET, GATA-3, TAK1, and FOXP3) associated with the immune response were found to be significantly differentially expressed in UVJs of Group L than Group S hens. In addition, four SNPs were identified in intron 1 of TGFβ3, and these SNPs were significantly associated with DF traits (P < 0.05). Furthermore, we identified multi-copy and copy number variants (CNVs) in chicken TGFβ3 and later determined significant associations between TGFβ3 CNVs and DF traits in hens. Specifically, TGFβ3 copy number exhibited a significant positive correlation with its expression (P < 0.05). Collectively, our results suggest that chicken DF traits may be regulated by the expression of TGFβ3 in UVJ. Meanwhile, the copy number variation in the TGFβ3 gene identified in this study seems to be one marker for DF traits.


Chemoimmunotherapy of MC-induced mouse sarcomas with human recombinant interleukin 2 and cyclophosphamide: age-dependent decline of the therapeutic efficacy.
Age-dependent decline of the anti-tumour efficacy of local IL-2 immunotherapy and chemoimmunotherapy utilizing human recombinant interleukin 2 and cyclophosphamide was investigated in B10 mice bearing syngeneic MC-induced sarcoma. Repeated peritumoral injections of rIL-2 substantially inhibited growth of transplantable MC-induced sarcomas in syngeneic young adult mice whereas no effect was observed in the aged mice. Chemoimmunotherapy of the MC-induced sarcomas in the young adult and in the aged mice treated with cyclophosphamide plus rIL-2 revealed that subthreshold doses of CY were capable of significantly potentiating the immunotherapeutic effect of rIL-2 in young adult mice but not in the aged mice.


Growing teratoma syndrome in mixed hepatoblastoma with teratoid features.
Mixed epithelial mesenchymal (MEM) hepatoblastoma with teratoid features is rare histological variant of hepatoblastoma and described in case reports. Growing teratoma syndrome (GTS) is a rare and often unrecognised phenomenon generally associated with less than 5% of germ cell tumour. It is defined by enlarging tumour mass which is generally mature teratoma with normal or significantly decreasing tumour markers during chemotherapy. The treatment outcomes in GTS are dependent on early recognition and complete surgical excision. We describe a rare case of MEM hepatoblastoma with teratoid features with GTS in an infant who had a delay in definitive management due to late diagnosis of GTS.


Arthothelium punctatum (Arthoniaceae, Arthoniales), A New Lichen Species from South Korea.
A total of 121 species of lichens belonging to the genus Arthothelium have been described to date, most of which have been found in tropical regions. Here, we describe the discovery of a novel Arthothelium species for the first time in South Korea. Until now, Arthothelium ruanum was the only Arthothelium species reported in South Korea. Among the 113 specimens collected in this study, we identified A. ruanum and a putative new species, Arthothelium punctatum (J. S. Park & J.-S. Hur, sp. nov.). The diagnostic characters of A. punctatum are as follows: apothecia punctate, shortly elongate to branched, small, 0.1-0.2 mm wide, hypothecium hyaline to pale brown and obovate to broadly ellipsoid, muriform ascospores, 29.5-44.6 × 12.2-18.2 μm. The new species was found in Mt. Seokbyeong at an altitude of 790 m on smooth bark. Upon phylogenic analysis, the putative new species, A. punctatum, was separated from other Arthothelium species although the specimens analyzed were clustered with Arthoniaceae in phylogenetic trees based on both the mitochondrial small subunit (mtSSU) sequence and combined mtSSU and nuclear ribosomal large subunit sequences. Our data clearly indicate that this species is a new species belonging to the family Arthoniaceae. To elucidate the taxonomic characteristics of the new species, we provide morphological descriptions and a distribution map.


Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma: results from two consecutive phase II studies.
Randomized studies comparing induction chemotherapy followed by surgical resection with radiation alone found that the neoadjuvant approach produces better results. So far, this latter modality has not been compared with standard concomitant chemoradiation. The objective of this report was to compare the results of two consecutive phase II studies: neoadjuvant chemotherapy followed by surgery or chemoradiation for the unresectable cases versus standard cisplatin-based chemoradiation. From February 1999 to July 1999, 41 patients with cervical carcinoma, stages IB2-IIIB, were treated with neoadjuvant chemotherapy. Treatment consisted of three 21-day courses of cisplatin 100 mg/m(2) on day 1 and gemcitabine 1000 mg/m(2) on days 1 and 8, followed by either surgery or concomitant chemoradiation for the non-operable cases. From August 1999 to December 1999, an equal number of patients having comparable clinicopathological characteristics were treated with six weekly courses of cisplatin 40 mg/m(2) during standard pelvic radiation. A total of 82 patients were analyzed. Both groups were similar with regard to age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, pretreatment hemoglobin levels, parametrial infiltration and performance status. In the neoadjuvant arm the overall response rate to induction chemotherapy was 95% (95% confidence interval 88% to 100%). Twenty-three patients had surgery and 14 underwent chemoradiation. In the definitive chemoradiation study, 38 patients completed treatment, the median number of cisplatin courses was six for a dose intensity of 33 mg/m(2)/week. Doses to points A and B were 85 Gy (range 68-95) and 55 Gy (range 51-65), respectively. Chemoradiation was delivered in 44.6 (range 28-113) days. Complete response rates after all treatment were similar: 97% and 87% in the neoadjuvant and chemoradiation groups, respectively. At a median follow-up of 28 (range 2-33) and 24 (range 3-30) months, respectively, there were no differences in overall survival. To date, 15 and 13 patients in the neoadjuvant and chemoradiation groups, respectively, have died of disease (P = 0.8567). The results of this non-randomized comparison suggest that induction chemotherapy followed by surgery or chemoradiation is at least as effective in terms of response and survival as standard cisplatin-based chemoradiation. A randomized study is needed to confirm these findings.


Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda.
Sleeping sickness (HAT) caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases. Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household.


RIPASA score: a new diagnostic score for diagnosis of acute appendicitis.
To determine the usefulness of RIPASA score for the diagnosis of acute appendicitis using histopathology as a gold standard. Cross-sectional study. Department of General Surgery, Combined Military Hospital, Kohat, from September 2011 to March 2012. A total of 267 patients were included in this study. RIPASA score was assessed. The diagnosis of appendicitis was made clinically aided by routine sonography of abdomen. After appendicectomies, resected appendices were sent for histopathological examination. The 15 parameters and the scores generated were age (less than 40 years = 1 point; greater than 40 years = 0.5 point), gender (male = 1 point; female = 0.5 point), Right Iliac Fossa (RIF) pain (0.5 point), migration of pain to RIF (0.5 point), nausea and vomiting (1 point), anorexia (1 point), duration of symptoms (less than 48 hours = 1 point; more than 48 hours = 0.5 point), RIF tenderness (1 point), guarding (2 points), rebound tenderness (1 point), Rovsing's sign (2 points), fever (1 point), raised white cell count (1 point), negative urinalysis (1 point) and foreign national registration identity card (1 point). The optimal cut-off threshold score from the ROC was 7.5. Sensitivity analysis was done. Out of 267 patients, 156 (58.4%) were male while remaining 111 patients (41.6%) were female with mean age of 23.5 ± 9.1 years. Sensitivity of RIPASA score was 96.7%, specificity 93.0%, diagnostic accuracy was 95.1%, positive predictive value was 94.8% and negative predictive value was 95.54%. RIPASA score at a cut-off total score of 7.5 was a useful tool to diagnose appendicitis, in equivocal cases of pain.


Little but Intense: Using a HIIT-Based Strategy to Improve Mood and Cognitive Functioning in College Students.
Looking for useful and motivational strategies for promoting healthy habits and improving cognitive functioning in young populations, the aim of the present study was to determine if a single bout of high-intensity interval exercise could stimulate mood and working memory in college students. A total of 25 male subjects (mean ± SD, age: 21.7 ± 2.1 years; height: 1.77 ± 0.06 m; weight: 72.6 ± 8.4 kg; body mass index: 23.1 ± 1.4 kg/m2; VO2peak: 47.1 ± 9.3 mL/kg/min) participated voluntarily in this study. Participants underwent a high-intensity interval exercise consisting of 10 × 1 min of cycling at VO2peak power output. The Profile of Mood States (POMS) questionnaire and Digit Span Test (DST) were administered at three assessment time points: (a) pre-intervention assessment, (b) post-intervention assessment, and (c) 30 min post-intervention. The mood states decreased significantly after exercise; however, a significant increase in mood was found after 30 min of recovery. A significant post-exercise increase in DST performance was observed; moreover, DST scores obtained 30 min after exercise remained higher than those assessed pre-exercise. In conclusion, a single bout of HIIT induces acute positive changes in mood states in male college students and seems to be a powerful stimulus for cognitive functioning.


Mobilising communities for Aedes aegypti control: the SEPA approach.
Camino Verde (the Green Way) is an evidence-based community mobilisation tool for prevention of dengue and other mosquito-borne viral diseases. Its effectiveness was demonstrated in a cluster-randomised controlled trial conducted in 2010-2013 in Nicaragua and Mexico. The common approach that brought functional consistency to the Camino Verde intervention in both Mexico and Nicaragua is Socialisation of Evidence for Participatory Action (SEPA). In this article, we explain the SEPA concept and its theoretical origins, giving examples of its previous application in different countries and contexts. We describe how the approach was used in the Camino Verde intervention, with details that show commonalities and differences in the application of the approach in Mexico and Nicaragua. We discuss issues of cost, replicability and sustainability, and comment on which components of the intervention were most important to its success. In complex interventions, multiple components act in synergy to produce change. Among key factors in the success of Camino Verde were the use of community volunteers called brigadistas, the house-to-house visits they conducted, the use of evidence derived from the communities themselves, and community ownership of the undertaking. Communities received the intervention by random assignment; dengue was not necessarily their greatest concern. The very nature of the dengue threat dictated many of the actions that needed to be taken at household and neighbourhood levels to control it. But within these parameters, communities exercised a large degree of control over the intervention and displayed considerable ingenuity in the process. ISRCTN27581154 .


Predicting injury risk in adolescent football players: the importance of psychological variables.
Explored the relationship of anger/aggression, attention, and stressful life events to injury while addressing the methodological limitations of prior studies. An additional objective was to determine whether the relationship of stressful life events to injury is mediated either by anger (directed either inward or outward) or by impaired attention, either vigilant (broad, external) or focused (narrow, internal). At the beginning of summer practice, 120 first-string high school football players completed measures of anger (Framingham Anger Scale), vigilant attention (Symbol Digit Modalities test), focused attention (Pursuit subtest, MacQuarrie Test of Mechanical Ability), and stressful life events (abbreviated form of the Social Readjustment Rating Scale as modified for use with adolescents by Coddington, 1972). Players were then followed through one season to identify those injured. Logistic regression indicated that high anger directed outward (p < .05) and low focused attention (p < .01) increased injury risk, while stressful life events and vigilant attention interacted. Injury risk was elevated when recent stress was present (p < .05), and increased as vigilance decreased, suggesting that stressful life events elevate injury risk by reducing vigilance.


Tonic Electromyogram Density in Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease.
Both Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. No significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (β = 0.552, P < 0.001) and RBD (β = 0.433, P < 0.001) as predictors of higher tonic EMG density. Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.


Do chlorhexidine and ethanol improve bond strength and durability of adhesion of fiber posts inside the root canal?
The aim was to investigate the effects of chlorhexidine and ethanol pretreatment of the root canal on push-out bond strengths and durability of adhesion of fiber posts luted with two different adhesive strategies. One hundred twenty human anterior teeth were endodontically treated. After post space preparation, the root canals were irrigated using 1 % sodium hypochlorite (NaOCl) applied with passive ultrasonic irrigation followed by distilled water (control). In pretreatment (PT) group, chlorhexidine (CHX) root canals were irrigated using 2 % chlorhexidine; and in the PT group, 99 % ethanol was used prior application of the luting agent. Two different post-and-luting systems with an etch-and-rinse (CX) adhesive approach (n = 60) and a self-adhesive resin cement (RX; n = 60) were inserted into the root canals. Bond strengths were evaluated initially and after thermocycling and storage for 6 months using push-out tests. Bond strength was significantly affected by the adhesive strategy (p < 0.0005), the pretreatment (p < 0.0005) and the location inside the root canal (p < 0.0005; repeated measurement ANOVA). Ethanol significantly increased bond strengths irrespective of the luting agent used compared to the control and CHX group (p < 0.05; Tukey's B). Ethanol significantly increased bond strength of the CX and the RX system inside the root canal and could be recommended as a final rinse for luting fiber posts using an ethanol-based etch-and-rinse adhesive system or self-adhesive resin cement. PT of the root canal using ethanol seems to facilitate adhesive luting of fiber posts with the tested adhesive system and luting cements.


Low-cost observations and experiments return a high value in plant phenology research.
Plant ecologists in the Anthropocene are tasked with documenting, interpreting, and predicting how plants respond to environmental change. Phenology, the timing of seasonal biological events including leaf-out, flowering, fruiting, and leaf senescence, is among the most visible and oft-recorded facets of plant ecology. Climate-driven shifts in plant phenology can alter reproductive success, interspecific competition, and trophic interactions. Low-cost phenology research, including observational records and experimental manipulations, is fundamental to our understanding of both the mechanisms and effects of phenological change in plant populations, species, and communities. Traditions of local-scale botanical phenology observations and data leveraged from written records and natural history collections provide the historical context for recent observations of changing phenologies. New technology facilitates expanding the spatial, taxonomic, and human interest in this research by combining contemporary field observations by researchers and open access community science (e.g., USA National Phenology Network) and available climate data. Established experimental techniques, such as twig cutting and common garden experiments, are low-cost methods for studying the mechanisms and drivers of plant phenology, enabling researchers to observe phenological responses under novel environmental conditions. We discuss the strengths, limitations, potential hidden costs (i.e., volunteer and student labor), and promise of each of these methods for addressing emerging questions in plant phenology research. Applied thoughtfully, economically, and creatively, many low-cost approaches offer novel opportunities to fill gaps in our geographic, taxonomic, and mechanistic understanding of plant phenology worldwide.


Inhibition of miR-34a-5p protected myocardial ischemia reperfusion injury-induced apoptosis and reactive oxygen species accumulation through regulation of Notch Receptor 1 signaling.
Myocardial ischemia-reperfusion (I/R) injury is leading cause of death worldwide. miR-34a-5p was up-regulated in myocardial ischemia-reperfusion injury rats. We aim to explore how miR-34a-5p inhibition protected myocardium against I/R injury in both cell and animal models. In vivo rat and in vitro cell model were firstly constructed. quantitative real-time polymerase chain reaction was employed to investigate expression of miR-34a-5p and its target genes. Functional assays were conducted to detect the impact of miR-34a-5p on myocardial I/R injury. Enzyme-linked immunosorbent assay was performed to validate the expression levels of marker proteins of ischemia-reperfusion I/R-induced myocardial injury. MTT was performed to assess the cell viability and flow cytometry was utilized to detect cell apoptosis and reactive oxygen species accumulation. The interaction between miR-34a-5p and Notch Receptor 1 were also examined through luciferase reporter assay. miR-34a-5p was up-regulated post-reperfusion at rat myocardium. miR-34a-5p inhibitor attenuated myocardial ischemia-reperfusion injury, as shown by decreasing apoptosis rate, reducing infarct size and reactive oxygen species accumulation. In in vitro cell model, miR-34a-5p inhibitor also promoted cell proliferation, inhibited cell apoptosis and reactive oxygen species accumulation through targeting Notch Receptor 1 signaling. Our results revealed that miR-34a-5p knocking down attenuated myocardial I/R injury by promoting Notch Receptor 1 signaling-mediated inhibition of reactive oxygen species accumulation and cell apoptosis. Hence, miR-34a-5p might be a potential target for treatment of myocardial ischemia-reperfusion injury.


Effect of regional lung inflation on ventilation heterogeneity at different length scales during mechanical ventilation of normal sheep lungs.
Heterogeneous, small-airway diameters and alveolar derecruitment in poorly aerated regions of normal lungs could produce ventilation heterogeneity at those anatomic levels. We modeled the washout kinetics of (13)NN with positron emission tomography to examine how specific ventilation (sV) heterogeneity at different length scales is influenced by lung aeration. Three groups of anesthetized, supine sheep were studied: high tidal volume (Vt; 18.4 ± 4.2 ml/kg) and zero end-expiratory pressure (ZEEP) (n = 6); low Vt (9.2 ± 1.0 ml/kg) and ZEEP (n = 6); and low Vt (8.2 ± 0.2 ml/kg) and positive end-expiratory pressure (PEEP; 19 ± 1 cmH(2)O) (n = 4). We quantified fractional gas content with transmission scans, and sV with emission scans of infused (13)NN-saline. Voxel (13)NN-washout curves were fit with one- or two-compartment models to estimate sV. Total heterogeneity, measured as SD[log(10)(sV)], was divided into length-scale ranges by measuring changes in variance of log(10)(sV), resulting from progressive filtering of sV images. High-Vt ZEEP showed higher sV heterogeneity at <12- (P < 0.01), 12- to 36- (P < 0.01), and 36- to 60-mm (P < 0.05) length scales compared with low-Vt PEEP, with low-Vt ZEEP in between. Increased heterogeneity was associated with the emergence of low sV units in poorly aerated regions, with a high correlation (r = 0.95, P < 0.001) between total heterogeneity and the fraction of lung with slow washout. Regional mean fractional gas content was inversely correlated with regional sV heterogeneity at <12- (r = -0.67), 12- to 36- (r = -0.74), and >36-mm (r = -0.72) length scales (P < 0.001). We conclude that sV heterogeneity at length scales <60 mm increases in poorly aerated regions of mechanically ventilated normal lungs, likely due to heterogeneous small-airway narrowing and alveolar derecruitment. PEEP reduces sV heterogeneity by maintaining lung expansion and airway patency at those small length scales.


Phase modulation-based response-inhibition outcome prediction in translational scenario of stop-signal task.
In this paper, a method is proposed to predict the resting-state outcomes of participants based on their electroencephalogram (EEG) signals recorded before the successful /unsuccessful response inhibition. The motivation of this study is to enhance the shooter performance for shooting the target, when their EEG patterns show that they are ready. This method can be used in brain-computer interface (BCI) system. In this study, multi-channel EEG from twenty participants are collected by the electrodes placed at different scalp locations in resting-state time. The EEG trials are used to predict two possible outcomes: successful or unsuccessful stop. Four classifiers (QDC, KNNC, PARZENDC, LDC) are used in this study to evaluation the accuracy of our system. Based on the collected time-domain EEG signals, the phase locking value (PLV) from 5-pair electrodes are calculated and then used as the feature input for the classifiers. Our experimental results show that the proposed method prediction accuracy (leave-one-out) was obtained 95% by QDC classifier.


Abciximab-induced acute profound thrombocytopenia postpercutaneous coronary intervention.
Abciximab (c7E3 Fab) is one of the three potent intravenous glycoprotein IIb/IIIa receptor inhibitors (along with eptifibatide and tirofiban) that have shown significant positive outcomes when used in patients with intracoronary thrombus. However, major side effects have been reported with its use including hypotension, major bleeding and thrombocytopenia. This case is a 53-year-old man presenting with acute chest pain diagnosed with non-ST-elevation myocardial infarction, who underwent percutaneous coronary intervention with abciximab and heparin infusion and developed acute profound thrombocytopenia (platelet count <20,000/L) within 9 hours of infusion. This case demonstrates the importance of routinely monitoring the platelet count prior to and 2-4 hours following abciximab infusion and differentiating other causes of acute profound thrombocytopenia, particularly pseudothrombocytopenia and heparin-induced thrombocytopenia.


[Echinococcosis in pregnancy. A rare differential diagnosis in cystic intra-abdominal tumors in pregnancy].
Pregnancy and intraabdominal masses rarely cointcidate. Therapeutical consequences are associated with possible complications such as intraabdominal pain, torquation of cystic tumors, rupture of cystic masses and pelvic inflammation. In less than 5% of the cases a malignant process during pregnancy can be expected. Prior to therapy of intraabdominal masses patients from typical endemic areas ought to be checked up for parasitic infections such as cystic echinococcosis treated specifically. Based on the following case report we present the epidemiology, diagnosis and therapy of cystics echinococcosis in pregnancy.


Supercritical Fluid Extraction of Pyrrolidine Alkaloid from Leaves of Piper amalago L.
Supercritical fluid extraction was used to extract the alkaloid N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl]pyrrolidine from leaves of Piper amalago L. A three-level orthogonal array design matrix, OAD OA9(34), was used for optimization of the parameters of supercritical extraction of the alkaloid, employing supercritical carbon dioxide: extraction time (20, 40, and 60 min), temperature (40, 50, and 60°C), pressure (150, 200, and 250 bar), and the use of cosolvents (ethanol, methanol, and propyleneglycol). All parameters had significant effect on the alkaloid yield. The alkaloid yield after 60 min of extraction without cosolvents at 9 different conditions (32) in terms of temperature (40, 50, and 60°C) and pressure (150, 200, and 250 bar) was also evaluated. The optimal yield (≈3.8 mg g-1) was obtained with supercritical CO2 + methanol (5% v : v) at 40°C and 200 bar for 60 min of extraction.


Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT).
Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person's control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges.


Hydrogen Induced Etching Features of Wrinkled Graphene Domains.
Wrinkles are observed commonly in CVD (chemical vapor deposition)-grown graphene on Cu and hydrogen etching is of significant interest to understand the growth details, as well as a practical tool for fabricating functional graphene nanostructures. Here, we demonstrate a special hydrogen etching phenomenon of wrinkled graphene domains. We investigated the wrinkling of graphene domains under fast cooling conditions and the results indicated that wrinkles in the monolayer area formed more easily compared to the multilayer area (≥two layers), and the boundary of the multilayer area tended to be a high density wrinkle zone in those graphene domains, with a small portion of multilayer area in the center. Due to the site-selective adsorption of atomic hydrogen on wrinkled regions, the boundary of the multilayer area became a new initial point for the etching process, aside from the domain edge and random defect sites, as reported before, leading to the separation of the monolayer and multilayer area over time. A schematic model was drawn to illustrate how the etching of wrinkled graphene was generated and propagated. This work may provide valuable guidance for the design and growth of nanostructures based on wrinkled graphene.


Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.
Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.


Ontogeny of glutamic acid decarboxylase gene expression in the mouse pancreas.
Using two RT-PCR quantitative assays, we measured the pancreatic expression of the two isoforms of glutamic acid decarboxylase in the foetus, newborn and 14-, 21- and 35-day-old male and female NOD and C57BL/6 mice. In the C57BL/6 mouse, GAD 67 pancreatic expression is stable; in NOD mice, GAD 67 expression is similar to that found in control mice, except at 5 weeks of age, when pancreatic GAD 67 expression is about 2.5 times higher than in C57BL/6 mice. The pancreatic expression of GAD 65 is under the detection limit of the assay until 5 weeks of age. The overexpression of GAD 67 characterized in pancreas from 5-week-old NOD mice could be the result of beta cell hyperactivity, previously reported in this mouse strain.


Improving quality of care in oncology through healthcare payment reform.
To provide an overview of alternative payment models (APMs) and describe how leading national organizations involved with oncology care and payment are linking quality improvement initiatives and payment reform. Literature review. For this review, we summarized the literature on APMs and their goals of improving healthcare quality while jointly controlling the cost of care. We described the types of APMs that have been examined in the real-world setting, specifically in the area of oncology, and how they have affected the quality of oncology care. Currently, the following types of APMs are actively being explored by public- and private-sector insurers, specifically in oncology: accountable care organizations, bundled payments, clinical pathways, and patient-centered medical homes. To a great extent, the driving force behind implementing APMs tied to quality can be attributed to the initiatives of several leading national organizations, including the National Academy of Medicine, the American Society of Clinical Oncology, the National Committee for Quality Assurance, HHS, and CMS. Real-world evidence of APMs shows that progress is being made toward improving the quality of oncology care in the United States while simultaneously reducing costs. The effective pairing of quality initiatives with healthcare reimbursement structures will likely be key to the long-term success of such APMs.


Oleic Acid Uptake Reveals the Rescued Enterocyte Phenotype of Colon Cancer Caco-2 by HT29-MTX Cells in Co-Culture Mode.
Gastrointestinal epithelium is the unique route for nutrients and for many pharmaceuticals to enter the body. The present study aimed to analyze precisely whether co-culture of two colon cancer cell lines, mucus-producing cells HT29-MTX and enterocyte-like Caco-2 cells, ameliorate differentiation into an in vitro intestinal barrier model and the signaling pathways involved. Differentiated Caco-2 cells gene datasets were compared first to intestinal or cancer phenotypes and second to signaling pathway gene datasets. Experimental validations were performed in real-time experiments, immunochemistry, and gene expression analyses on Caco-2 versus co-cultures of Caco-2 and HT29-MTX (10%) cells. Partial maintenance of cancer-cell phenotype in differentiated Caco-2 cells was confirmed and fatty acids merged as potential regulators of cancer signaling pathways. HT29-MTX cells induced morphological changes in Caco-2 cells, slightly increased their proliferation rate and profoundly modified gene transcription of phenotype markers, fatty acid receptors, intracellular transporters, and lipid droplet components as well as functional responses to oleic acid. In vitro, enterocyte phenotype was rescued partially by co-culture of cancer cells with goblet cells and completed through oleic acid interaction with signaling pathways dysregulated in cancer cells.


The temperature sensitivity of soil organic carbon decomposition is greater in subsoil than in topsoil during laboratory incubation.
The turnover of soil organic carbon (SOC) in cropland plays an important role in terrestrial carbon cycling, but little is known about the temperature sensitivity (Q 10) of SOC decomposition below the topsoil layer of arable soil. Here, samples of topsoil (0-20 cm) and subsoil (20-40 cm) layers were obtained from paddy fields and upland croplands in two regions of China. Using a sequential temperature changing method, soil respiration rates were calculated at different temperatures (8 °C to 28 °C) and fitted to an exponential equation to estimate Q 10 values. The average SOC decomposition rate was 59% to 282% higher in the topsoil than in the subsoil layer because of higher labile carbon levels in the topsoil. However, Q 10 values in the topsoil layer (5.29 ± 1.47) were significantly lower than those in the subsoil layer (7.52 ± 1.84). The pattern of Q 10 values between the topsoil and subsoil was significantly negative to labile carbon content, which is consistent with the carbon quality-temperature hypothesis. These results suggest that the high temperature sensitivity of SOC decomposition in the subsoil layer needs to be considered in soil C models to better predict the responses of agricultural SOC pools to global warming.


A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second- Line Therapy in Patients with Advanced Gastric Cancer
Objective: We aimed to evaluate the effectiveness of an mEOX (modified epirubicin, oxaliplatin plus capecitabine) regimen as second line therapy after failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods: Gastic cancer patients for whom first-line therapy was unsuccessful and who subsequently received mEOX (epirubicin 50 mg/ m2 on day 1, oxaliplatin 85 mg/m² day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every 3 weeks until disease progression or unacceptable toxicity, were retrospectively analyzed. Results: The study population comprised 129 cases with a median age of 55 years (range= 27-78), the majority being male (76 %). Most (75.2%) had ≥ 2 sites of metastasis. The median number of chemotherapy courses was five (range= 2–9). Forty-nine achieved a partial response and 33 showed stable disease, resulting in a ORR (overall response rate) of 38% and a DCR (disease control rate) of 63.6%. The most frequent features of grade 3-4 hematological and non-hematological toxicity were neutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients suffered death due to toxicity. The median PFS was 4.7 months (95% CI, 4.1–5.3) and the OS was 7.4 months (95% CI, 6.3–8.5). On multivariate analysis, age ≥ 60 years and ECOG performance status (0-1) were independent prognostic factors affecting PFS and OS. Conslusions: In advanced gastric cancer patients, who progress after first line chemotherapy and have an ECOG performance status of 0-1, mEOX is a well tolerated triple regimen associated with a promising OS and PFS.


Peptidoglycan hydrolases of Bacillus subtilis 168.
There are multiple peptidoglycan hydrolases associated with Bacillus subtilis 168 and these potentially lethal enzymes have been implicated in a number of important cellular processes. Several enzymes have been studied at the molecular level and their structural genes characterized. This information has begun to identify roles for individual enzymes in motility, cell separation, differentiation, and phage lysis. It has become apparent that in many cases important autolytic functions can be performed by more than one enzyme, so the complex web of mutually compensatory components can be unraveled only by making multiple mutants. One such multiple mutant has revealed the presence of several previously unknown minor autolysins, the functions of which are currently obscure.


Dissecting quantitative trait loci into opposite blood pressure effects on Dahl rat chromosome 8 by congenic strains.
Our previous linkage analyses showed that there was likely a quantitative trait locus (QTL) for blood pressure (BP) on chromosome 8 (Chr 8) in the strain comparison between the Dahl salt-sensitive (S) and the Lewis (LEW) rats. The current work is to delineate the chromosome interval harboring this QTL by using congenic strains with different chromosome substitutions. Two congenic strains were produced by replacing different segments of the S rats with the homologous segments of the LEW rats. A genome-wide marker screening was utilized to accelerate this process. The two strains generated are designated as C8S.L1 and C8S.L2, respectively. BPs of the rats were measured by telemetry. C8S.L1 showed a BP lower than that of S rats. In contrast, C8S.L2 did not have chromosome overlaps with C8S.L1, but unexpectedly, exhibited a BP-raising effect, higher than that of S rats. There are at least two QTLs present in a section of Chr 8 that possess opposite BP effects. The current congenic work reveals not only the presence of QTLs, but the complexity of QTLs on BP. The novel congenic strain with hypertension more severe than S provides a new model for studies in elucidating physiological mechanisms controlling BP.


A study of forearm versus finger stick glucose monitoring.
New glucose monitoring systems are now being launched into the market that offer the patient the option to test from an alternate site (forearm) with less pain. What is not clearly understood by patients and Health Care Providers is whether glucose measurements taken from the forearm are the same as the measurements taken from the finger. The objective of this study was to determine if results from the forearm are the same as results from the finger in normal use by the diabetic patient over a day. In clinical studies conducted in four physician's offices, patients were asked to measure their glucose from their forearm and finger ten times a day for ten days. The patients for this evaluation used the TheraSense FreeStyle glucose monitoring system. A total of 190 patients (of which 30% were type 1 and 70% type 2 diabetics) participated in this study. Patients also concluded their participation in this study with a post study questionnaire. A total of 18,036 data points were collected and used for analysis. Data was separated into four groups: preprandial, 1-h postprandial, 2-h postprandial, and bedtime. In three of the four groups, the mean bias was less than 1 mg/dL or %, whereas the 1-h postprandial group showed a mean bias of -6.02 mg/dL or %. The differences in bias between the 1-h postprandial to the preprandial and the 1-h postprandial to the 2-h postprandial, were statistically significant with a p value of <0.0001. Comparison of bias at 2-h postprandial to the preprandial bias was not statistically significant with a p value of 0.8073, indicating that the 2-h postprandial had an overall mean bias, the same as the preprandial. The 1-h postprandial results indicate that patients who test during this period of time could expect to see significant differences between their forearm and finger measurements. Patients who test during this time period should only test using their finger since this would best represent their true glucose. Patients who would test during periods identified as preprandial and 2-h postprandial could expect to see small differences between their forearm and finger measurements. These differences are also not dependent on the method by which patients use to control their disease.