Health-related quality of life (HRQOL) in end stage renal disease (ESRD) patients over 65 years.
The aim of the study was to assess Health Related Quality of Life (HRQOL) of elderly patients on renal replacement therapy (RRT) of our region, and to identify socio-demographic and clinical variables which influence it. We also attempted to compare HRQOL of transplant patients, with that of chronic hemodialysis patients. Cross-sectional study. Institutional Hospital Nephrology Unit. All patients from 9 of the 10 hemodialysis centres in our region, aged 65 years or more, who had been on RRT (chronic hemodialysis and kidney transplantation) for at least three months, showing no cognitive problems, were included. The sample included 124 patients. These patients participated in a structured interview using two generic HRQOL questionnaires: Sickness Impact Profile and SF-36 Health Survey. Karnofsky Scale, Comorbidity Index, socio-demographic and clinical data, were also collected. The median age was 71 years (range 65-75); 55.6% of the patients were male; 19.8% of the sample were transplant patients and 80.2%, hemodialysis patients (only 2% on renal transplant waiting list); 69.2% had a low-intermediate socio-economic level, 52.9% had elementary studies, and 10.6% lived alone. Transplant patients had higher HRQOL than hemodialysis patients. Women had lower HRQOL than men. A higher economic level, higher educational level, higher Karnofsky Performance Scale, and lower Comorbidity Index score, were associated with higher HRQOL. The good HRQOL of elderly transplant patients, in comparison with hemodialysis patients, is an important reason for advising kidney transplants in elderly patients. Economic and educational levels, functional status and comorbidity are variables which influence the HRQOL of these patients.


Rate of deterioration of renal function in juvenile nephronophthisis.
The rate of deterioration of renal function was determined in 29 patients with juvenile nephronophthisis presenting before the age of 18.5 years. The analysis was based on 618 serial determinations of serum creatinine (SCR). By application of a new statistical method the time elapsing between different successive SCR levels was calculated. A more or less homogeneous increase of SCR was noted starting from the time when a SCR of 4 mg/dl was reached. The median time elapsing between an SCR of 2 and 4 mg/dl was 32 months, between 4 and 6 mg/dl 10 months and between 6 and 8 mg/dl 5 months. The median age at the start of renal replacement therapy or death due to uraemia, evaluated by survival analysis, was similar in both sexes.


Regional multi-compartment ecological risk assessment: Establishing cadmium pollution risk in the northern Bohai Rim, China.
Ecological risk assessment (ERA) has been widely applied in characterizing the risk of chemicals to organisms and ecosystems. The paucity of toxicity data on local biota living in the different compartments of an ecosystem and the absence of a suitable methodology for multi-compartment spatial risk assessment at the regional scale has held back this field. The major objective of this study was to develop a methodology to quantify and distinguish the spatial distribution of risk to ecosystems at a regional scale. A framework for regional multi-compartment probabilistic ecological risk assessment (RMPERA) was constructed and corroborated using a bioassay of a local species. The risks from cadmium (Cd) pollution in river water, river sediment, coastal water, coastal surface sediment and soil in northern Bohai Rim were examined. The results indicated that the local organisms in soil, river, coastal water, and coastal sediment were affected by Cd. The greatest impacts from Cd were identified in the Tianjin and Huludao areas. The overall multi-compartment risk was 31.4% in the region. The methodology provides a new approach for regional multi-compartment ecological risk assessment.


Dialysis of the goat semen and its effect on the quality of frozen/thawed spermatozoa processed in the presence of egg yolk.
The aim of the present study was to analyze the effect of dialysis on the quality of frozen/thawed buck semen. Ejaculates (n = 15) from three Saanen bucks were divided into three experimental groups. Semen in Group Ce (centrifugation) was processed by standard method and washed two times at 1.085 × g for 20 min. During this time, the diluted control semen (Co) was stored at room temperature. Semen in Group D was dialyzed using 300 kDa cut-off semi-permeable cellulose tubing. The semen from all groups was diluted with extender containing 20% egg yolk and frozen in liquid nitrogen vapor. After thawing, semen samples were evaluated by microscopic and biochemical analyses. Phospholipase A2 was in amounts that was 72.0 ± 11.7% less after dialysis and 21.3 ± 10.0% less after washing with centrifugation compared to the control semen (P < 0.05). Spermatozoa from Group Co had a lesser motility and viability and greater percentage of morphological abnormal spermatozoa in comparison to Groups D and Ce at 3 h after thawing and incubation on 37 °C. At the same time motility and percentage of HOST positive spermatozoa were greater in Group Ce compared with D (P < 0.05). There, however, was no difference in morphology and viability (CFDA/PI analysis) of spermatozoa between Ce and D group. Results from the present study suggest the dialysis is the promising alternative method for reducing phospholipase A2 in the buck semen before cryopreservation.


DNA methylome of primary spermatocyte reveals epigenetic dysregulation associated with male sterility of cattleyak.
DNA cytosine methylation modification in the germline is of particular importance since it is a highly heritable epigenetic mark. Although cytosine methylation has been analyzed at the genome-scale for several mammalian species, our knowledge of DNA methylation patterns and the mechanisms underlying male hybrid sterility is still limited in domestic animals such as cattleyak. Here we for the first time show the genome-wide and single-base resolution landscape of methylcytosines (mC) in the primary spermatocyte (PSC) genome of yak with normal spermatogenesis and the inter-specific hybrid cattleyak with male infertility. A comparative investigation revealed that widespread differences are observed in the composition and patterning of DNA cytosine methylation between the two methylomes. Global CG or non-CG DNA methylation levels, as well as the number of mC sites, are increased in cattleyak compared to yak. Notably, the DNA methylome in cattleyak PSC exhibits promoter hypermethylation of meiosis-specific genes and piRNA pathway genes with respect to yak. Furthermore, major retrotransposonson classes are predominantly hypermethylated in cattleyak while those are fully hypomethylated in yak. KEGG pathway enrichment indicates Rap1 signaling and MAPK pathways may play potential roles in the spermatogenic arrest of cattleyak. Our present study not only provides valuable insights into distinct features of the cattleyak PSC methylome but also paves the way toward elucidating the complex, yet highly coordinated epigenetic modification during male germline development for inter-specific hybrid animals.


How granular should our explanations of fantastic fiction be?
Explaining the reasons behind the success of various kinds of fiction is important, but how granular should our explanations be? I suggest that using a less granular, more general hypothesis would allow avoiding some pitfalls, such as using the concept of "imaginary world," which eludes precise definitions.


Does Stone Removal Help Patients with Recurrent Urinary Tract Infections?
We evaluated the impact of surgical extraction of nonobstructing asymptomatic stones on recurrent urinary tract infections and identified predictors of patients who may be rendered infection-free. We retrospectively reviewed charts to identify patients with recurrent urinary tract infections who underwent surgical stone extraction and were rendered stone-free. Demographic variables as well as procedure, infectious etiology, stone composition and the systemic inflammatory response syndrome rate were also recorded. Patients were divided into 2 groups. Group 1 had no evidence of recurrent infection following surgery while recurrent infection developed in group 2. Univariate analysis was performed using the Wilcoxon signed rank and Fisher exact tests. Logistic regression was used for multivariate analysis. We identified 120 patients with recurrent urinary tract infections and a nonobstructive renal stone. Surgical management included shock wave lithotripsy in 32% of cases, ureteroscopy in 7% and percutaneous nephrolithotomy in 61%. Of the 120 patients 58 (48%) remained infection-free after surgery while 62 (52%) experienced recurrent infection. Factors associated with a higher risk of recurrent infections included type 2 diabetes mellitus (OR 1.73, p = 0.01), hypertension (OR 2.8, p = 0.007) and black ethnicity (OR 13.7, p = 0.009). Escherichia coli infections were more likely to resolve (OR 0.34, p = 0.01). In contrast, Enterococcus infections were more likely to persist (OR 2.5, p = 0.04). On multiple logistic regression analysis only race, hypertension and E. coli infections were significant predictors of infection clearance. Of patients with recurrent urinary tract infections and asymptomatic renal calculi 50% may be rendered infection-free following stone extraction. Patients with risk factors for recurrent infections after surgery should be counseled that stone extraction might not eradicate the infection.


Correction: Yao, Y., et al. Activation of Slit2/Robo1 Signaling Promotes Tumor Metastasis in Colorectal Carcinoma through Activation of the TGF-β/Smads Pathway. Cells 2019, 8, 635.
The author wishes to make the following correction to this paper [...].


Do we need cold plasma treated fruit and vegetable juices? A case study of positive and negative changes occurred in these daily beverages.
Cold atmospheric pressure plasma (CAPP) is a prospective technology for various branches of industry. As such, much attention has been recently paid towards the use of CAPPs for treating fruit and vegetable beverages as they do not need any more to be thermally pasteurized or sanitized. However, this application of CAPPs is not only limited to the improvement of their shelf-life. It could also contribute to the enhancement of their nutritional properties and anticancer activity. This could be achieved due to the presence of numerous reactive oxygen and nitrogen species (RONS), produced at the plasma-liquid interface, that might contribute to the increase of the content of nutritional and bioactive compounds, simply upgrading the juices. In this context, the present review focuses on the recent advances in the CAPP-based technology towards the processing of fruit and vegetable juices. As such, a series of different CAPP-based reaction-discharge systems and their configurations are reviewed and set together with the physicochemical, nutritional, and antimicrobial characteristics of the CAPP-treated juices, providing an useful insight into the perspective development of emerging CAPP technology.


Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade.
Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059-1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy.


Correction: One Size Does Not Fit All: Assuming the Same Normal Body Temperature for Everyone is Not Justified.
[This corrects the article DOI: 10.1371/journal.pone.0245257.].


ZnO quantum dot-decorated carbon nanofibers derived from electrospun ZIF-8/PVA nanofibers for high-performance energy storage electrodes.
Hierarchical fibrous structures composed of ZnO quantum dots, amorphous carbons, and carbon nanofibers are synthesized via a single carbonization process of electrospun ZIF-8/PVA nanofibers. This newly designed electrode material for supercapacitors exhibits outstanding electrochemical performances with high capacitance, reliable rate capability, and long cycle life.


Frequent Somatic Mutation in Adult Intestinal Stem Cells Drives Neoplasia and Genetic Mosaicism during Aging.
Adult stem cells may acquire mutations that modify cellular behavior, leading to functional declines in homeostasis or providing a competitive advantage resulting in premalignancy. However, the frequency, phenotypic impact, and mechanisms underlying spontaneous mutagenesis during aging are unclear. Here, we report two mechanisms of genome instability in adult Drosophila intestinal stem cells (ISCs) that cause phenotypic alterations in the aging intestine. First, we found frequent loss of heterozygosity arising from mitotic homologous recombination in ISCs that results in genetic mosaicism. Second, somatic deletion of DNA sequences and large structural rearrangements, resembling those described in cancers and congenital diseases, frequently result in gene inactivation. Such modifications induced somatic inactivation of the X-linked tumor suppressor Notch in ISCs, leading to spontaneous neoplasias in wild-type males. Together, our findings reveal frequent genomic modification in adult stem cells and show that somatic genetic mosaicism has important functional consequences on aging tissues.


Photosynthesis and biochemical characterization of the green alga Chlamydopodium fusiforme (Chlorophyta) grown in a thin-layer cascade.
Photosynthesis, growth and biochemical composition of the biomass of the freshwater microalga Chlamydopodium fusiforme cultures outdoors in a thin-layer cascade were investigated. Gross oxygen production measured off-line in samples taken from the outdoor cultures was correlated with the electron transport rate estimated from chlorophyll a fluorescence measurements. According to photosynthesis measurements, a mean of 38.9 ± 10.3 mol of photons were required to release one mole of O2, which is 4.86 times higher than the theoretical value (8 photons per 1 O2). In contrast, according to the fluorescence measurements, a mean of 11.7 ± 0.74 mol of photons were required to release 1 mol of O2. These findings indicate that fluorescence-based photosynthesis rates may not be fully replace oxygen measurements to evaluate the performance of an outdoor culture. Daily gross biomass productivity was 0.3 g DW L-1 day-1 consistently for 4 days. Biomass productivity was strongly affected by the suboptimal concentration at which the culture was operated and by the respiration rate, as the substantial volume of culture was kept in the dark (about 45% of the total volume). As the cells were exposed to excessive light, the photosynthetic activity was mainly directed to the synthesis of carbohydrates in the biomass. In the morning, carbohydrate content decreased because of the dark respiration. Per contra, protein content in the biomass was lower at the end of the day and higher in the morning due to carbohydrate consumption by respiration. The data gathered in these trials are important for the future exploitation of Chlamydopodium fusiforme as a potential novel species in the field of microalgae for the production of bio-based compounds.


Hypoxic acclimation negatively impacts the contractility of steelhead trout (Oncorhynchus mykiss) spongy myocardium.
Cardiac stroke volume (SV) is compromised in Atlantic cod and rainbow trout following acclimation to hypoxia (i.e., 40% air saturation; ~8 kPa O2) at 10-12°C, and this is not due to changes in heart morphometrics or maximum achievable in vitro end-diastolic volume. To examine if this diminished SV may be related to compromised myocardial contractility, we used the work-loop method to measure work and power in spongy myocardial strips from normoxic- and hypoxic-acclimated steelhead trout when exposed to decreasing Po2 levels (21 to 1.5 kPa) at several frequencies (30-90 contractions/min) at 14°C (their acclimation temperature). Work required to lengthen the muscle, as during filling of the heart, was strongly frequency dependent (i.e., increased with contraction rate) but was not affected by hypoxic acclimation or test Po2. In contrast, although shortening work was less frequency dependent, this parameter and network (and power) 1) were consistently lower (by ~30-50 and ~15%, respectively) in strips from hypoxic-acclimated fish and 2) fell by ~40-50% in both groups from 20 to 1.5 kPa Po2, despite the already-reduced myocardial performance in the hypoxic-acclimated group. In addition, strips from hypoxic-acclimated trout showed a poorer recovery of net power (by ~15%) when returned to normoxia. These results strongly suggest that hypoxic acclimation reduces myocardial contractility, and in turn, may limit SV (possibly by increasing end-systolic volume), but that this diminished performance does not improve the capacity to maintain myocardial performance under oxygen limiting conditions.


Antinociceptive activity of salsolinol (racemate, R(+)-, S(-)-enantiomers): evidence of a peripheral mechanism.
The existence and the characteristics of the antinociceptive action of salsolinol (racemate) and its two R(+)- and S(-)-enantiomers were studied using different pain tests in mice. None of these drugs possessed a significant activity on the tests sensitive to central acting analgesics (hot-plate and tail-flick tests), either after systemic (i.p.) or central (i.c.v.) injections. However, injected i.p., they reduced the number of writhes induced by phenylbenzoquinone; the ED50 was 79 +/- 2, 73 +/- 2 and 61 +/- 2 mg/kg for racemate, R(+)- and S(-)-enantiomer respectively. This activity was not antagonized by naloxone. Moreover, racemate and S(-) reduced, only for the highest used active dose on the PBQ test (128 mg/kg, i.p.), the edema induced by an intraplantar injection of carrageenin. These results provide evidence of an analgesic activity independent of the endogenous opiate systems and involving a peripheral mechanism.


Nuclear receptor FXR, bile acids and liver damage: Introducing the progressive familial intrahepatic cholestasis with FXR mutations.
The nuclear receptor farnesoid X receptor (FXR) is the master regulator of bile acids (BAs) homeostasis since it transcriptionally drives modulation of BA synthesis, influx, efflux, and detoxification along the enterohepatic axis. Due to its crucial role, FXR alterations are involved in the progression of a plethora of BAs associated inflammatory disorders in the liver and in the gut. The involvement of the FXR pathway in cholestasis development and management has been elucidated so far with a direct role of FXR activating therapy in this condition. However, the recent identification of a new type of genetic progressive familial intrahepatic cholestasis (PFIC) linked to FXR mutations has strengthen also the bona fide beneficial effects of target therapies that by-pass FXR activation, directly promoting the action of its target, namely the enterokine FGF19, in the repression of hepatic BAs synthesis with reduction of total BA levels in the liver and serum, accomplishing one of the major goals in cholestasis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.


[Content of Osmolytes and Flavonoids under Salt Stress in Arabidopsis thaliana Plants Defective in Jasmonate Signaling].
The effects of the salt stress (200 mM NaCl) and exogenous jasmonic acid (JA) on levels of osmolytes and flavonoids in leaves of four-week-old Arabidopsis thaliana L. plants of the wild-type (WT) Columbia-0 (Col-0) and the mutant jin1 (jasmonate insensitive 1) with impaired jasmonate signaling were studied. The increase in proline content caused by the salt stress was higher in the Col-0 plants than in the mutant jin1. This difference was especially marked if the plants had been pretreated with exogenous 0.1 µM JA. The sugar content increased in response to the salt stress in the JA-treated WT plants but decreased in the jin1 mutant. Leaf treatment with JA of the WT plants but not mutant defective in jasmonate signaling also enhanced the levels of anthocyanins and flavonoids absorbed in UV-B range. The presence of JA increased salinity resistance of the Col-0 plants, since the accumulation of lipid peroxidation products and growth inhibition caused by NaCl were less pronounced. Under salt stress, JA almost did not render a positive effect on the jin1 plants. It is concluded that the protein JIN1/MYC2 is involved in control of protective systems under salt stress.


Action-effect learning in early childhood: does language matter?
Previous work showed that language has an important function for the development of action control. This study examined the role of verbal processes for action-effect learning in 4-year-old children. Participants performed an acquisition phase including a two-choice key-pressing task in which each key press (action) was followed by a particular sound (effect). Children were instructed to either (1) label their actions along with the corresponding effects, (2) verbalize task-irrelevant words, (3) or perform without verbalization. In a subsequent test phase, they responded to the same sound effects either under consistent or under inconsistent sound-key mappings. Evidence for action-effect learning was obtained only if action and effects were labeled or if no verbalization was performed, but not if children verbalized task-irrelevant labels. Importantly, action-effect learning was most pronounced when children verbalized the actions and the corresponding effects, suggesting that task-relevant verbal labeling supports the integration of event representations.


Alteration and recovery of appetitive behaviour following nerve section in the starfish Asterias rubens.
The starfish Asterias rubens is an invertebrate deuterostome whose nervous system shows remarkable regenerative properties. To understand when full functionality of a damaged part of the nervous system recovers, and to follow nerve regeneration in detail, we carried out behavioural experiments with 29 starfishes that had the nerve in one of the arms sectioned in a mid-arm position. Loss and recovery of normal behaviour was followed by video analysis of animal performance in an appetitive behavioural test. When compared to 13 control (unoperated) animals, the appetitive response of freshly sectioned animals is normal initially, progressively deteriorates up to 40 days after the lesion, and then gradually improves until 60 days, when recovery is complete. This is true only when one of the leading arms in the appetitive test is a sectioned arm; turning the starfish so that both the leading arms facing the prey are unlesioned, results in normal behaviour even at 40 days after the cut. Thus, regeneration is a multi-step process whose time course coincides with anatomical regeneration. At intermediate times the animals have coordination problems in an appetitive behaviour test and these give some insights into how arms may inter-communicate to organize concerted movements.


Long-acting insulin analog detemir displays reduced effects on adipocyte differentiation of human subcutaneous and visceral adipose stem cells.
Since treatment with insulin detemir results in a lower weight gain compared to human insulin, we investigated whether detemir is associated with lower ability to promote adipogenesis and/or lipogenesis in human adipose stem cells (ASC). Human ASC isolated from both the subcutaneous and visceral adipose tissues were differentiated for 30 days in the presence of human insulin or insulin detemir. Nile Red and Oil-Red-O staining were used to quantify the rate of ASC conversion to adipocytes and lipid accumulation, respectively. mRNA expression levels of early genes, including Fos and Cebpb, as well as of lipogenic and adipogenic genes, were measured at various phases of differentiation by qRT-PCR. Activation of insulin signaling was assessed by immunoblotting. ASC isolated from subcutaneous and visceral adipose tissue were less differentiated when exposed to insulin detemir compared to human insulin, showing lower rates of adipocyte conversion, reduced triglyceride accumulation, and impaired expression of late-phase adipocyte marker genes, such as Pparg2, Slc2a4, Adipoq, and Cidec. However, no differences in activation of insulin receptor, Akt and Erk and induction of the early genes Fos and Cebpb were observed between insulin detemir and human insulin. Insulin detemir displays reduced induction of the Pparg2 adipocyte master gene and diminished effects on adipocyte differentiation and lipogenesis in human subcutaneous and visceral ASC, in spite of normal activation of proximal insulin signaling reactions. These characteristics of insulin detemir may be of potential relevance to its weight-sparing effects observed in the clinical setting.


Autocrine DUSP28 signaling mediates pancreatic cancer malignancy via regulation of PDGF-A.
Pancreatic cancer remains one of the most deadly cancers with a grave prognosis. Despite continuous efforts to improve remedial values, limited progress has been made. We have reported that dual specificity phosphatase 28 (DUSP28) has a critical role of chemo-resistance and migration in pancreatic cancers. However, its mechanism remains unclear. Here, we further clarify the function of DUSP28 in pancreatic cancers. Analysis using a public microarray database and in vitro assay indicated a critical role of platelet derived growth factor A (PDGF-A) in pancreatic cancer malignancy. PDGF-A was positively regulated by DUSP28 expression at the mRNA and protein levels. Enhanced DUSP28 sensitized pancreatic cancer cells to exogenous PDGF-A treatment in migration, invasion, and proliferation. Transfection with siRNA targeting DUSP28 blunted the influence of administered PDGF-A by inhibition of phosphorylation of FAK, ERK1/2, and p38 signalling pathways. In addition, DUSP28 and PDGF-A formed an acquired autonomous autocrine-signaling pathway. Furthermore, targeting DUSP28 inhibited the tumor growth and migratory features through the blockade of PDGF-A expression and intracellular signaling in vivo. Our results establish novel insight into DUSP28 and PDGF-A related autonomous signaling pathway in pancreatic cancer.


Efficacy and safety of subcutaneous trastuzumab and intravenous trastuzumab as part of adjuvant therapy for HER2-positive early breast cancer: Final analysis of the randomised, two-cohort PrefHer study.
To assess efficacy (event-free survival, EFS) and safety in patients followed up for 3 years in the PrefHer study (NCT01401166). Post surgery and post chemotherapy in the (neo)adjuvant setting, patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer were randomised to receive four cycles of the subcutaneous form of trastuzumab (Herceptin® SC [H SC] via single-use injection device [Cohort 1] or delivery via a hand-held syringe from an SC Vial [Cohort 2]; 600 mg fixed dose) followed by four of the intravenous form of trastuzumab (Herceptin® [H IV]; 8 mg/kg loading, 6 mg/kg maintenance doses) in the adjuvant setting or vice versa every 3 weeks. Patients could have received H before randomisation. H was then continued to complete a total of 18 cycles, including any cycles received before randomisation. A total of 488 patients were randomised across both cohorts. After median follow-up of 36.1 months, 3-year EFS across both groups in the evaluable intention-to-treat population (467 patients) was 90.6% overall, 89.9% in Cohort 1, and 91.1% in Cohort 2. No new safety signals were identified during long-term follow-up, with only one cardiac serious adverse event in the safety population (483 patients). Three-year EFS data following H SC and H IV treatment are consistent with those reported by previous trials for H in the adjuvant setting. The overall safety profile during adjuvant treatment was as expected.


Homogeneous Elongation of N-Doped CNTs over Nano-Fibrillated Hollow-Carbon-Nanofiber: Mass and Charge Balance in Asymmetric Supercapacitors Is No Longer Problematic.
The hurdle of fabricating asymmetric supercapacitor (ASC) devices using a faradic cathode and a double layer anode is challenging due to the required large amount of active mass of anodic material compared to that of the cathodic material during mass balancing due to the large difference in capacitance values of the two electrodes. Here, the problem is addressed by engineering a negative electrode that furnishes an ultrahigh capacitance. An in situ developed metal-organic framework (MOF)-based thermal treatment is adopted to grow highly porous N-doped carbon nanotubes (CNTs) containing submerged Co nanoparticles over nano-fibrillated electrospun hollow carbon nanofibers (HCNFs). The optimized firstname.lastname@example.com furnishes an ultrahigh capacitance approaching 712 F g-1 with excellent rate capability. The capacitance reported from this work is the highest for any carbonaceous material reported to date. The email@example.com is further used to fabricate symmetric supercapacitors (SSCs), as well as ASC devices. Remarkably, both the SSC and ASC devices furnish incredible performances in all aspects of SCs, such as a high energy density, long cycle life, and high rate capability, displaying decent practical applicability. The energy density of the SSC device reaches as high as 20.13 W h kg-1 , whereas that of ASC approaches 87.5 W h kg-1 .


Prediction of All-Cause Mortality by the Left Atrial Volume Index in Patients With Normal Left Ventricular Filling Pressure and Preserved Ejection Fraction.
To describe the prevalence of left atrial (LA) enlargement (LAE) and its association with all-cause mortality in 10,719 patients with an early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') ratio-determined normal left ventricular (LV) filling pressure and preserved LV ejection fraction (LVEF). We evaluated 10,719 patients (deceased patients: n = 479; mean [SD] age, 65 [14] years; 60% male; surviving patients: n = 10,240; mean (SD) age, 54 (16) years; 48% male) with estimated normal LV filling pressure (E/e' ratio ≤ 8) and preserved LVEF (≥ 50%) to determine the impact of LA volume index (LAVi) on all-cause mortality during a mean (SD) follow-up of 2.2 (1.0) years. In the univariate analysis, with every milliliter per square meter increase in LAVi, all-cause mortality risk increased by 3% (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04; P < .001). After adjusting for covariates, LAVi (as a continuous variable) was an independent predictor of all-cause mortality (HR, 1.015; 95% CI, 1.005-1.026; P = .01). When LAVi was assessed as a categorical variable with normal LAVi (≤ 28 mL/m(2)) as the reference group, moderate LAVi (34-39 mL/m(2)) and severe LAVi (≥ 40 mL/m(2)) were independent predictors of all-cause mortality (HR, 1.34; 95% CI, 1.01-1.79; P = .04; and HR, 1.65; 95% CI, 1.18-2.29; P = .003, respectively). LAE was independently associated with an increased risk of all-cause mortality in our large cohort of 10,719 patients with normal LV filling pressure and preserved LVEF.


Control of leucine-dependent mTORC1 pathway through chemical intervention of leucyl-tRNA synthetase and RagD interaction.
Leucyl-tRNA synthetase (LRS) is known to function as leucine sensor in the mammalian target of rapamycin complex 1 (mTORC1) pathway. However, the pathophysiological significance of its activity is not well understood. Here, we demonstrate that the leucine sensor function for mTORC1 activation of LRS can be decoupled from its catalytic activity. We identified compounds that inhibit the leucine-dependent mTORC1 pathway by specifically inhibiting the GTPase activating function of LRS, while not affecting the catalytic activity. For further analysis, we selected one compound, BC-LI-0186, which binds to the RagD interacting site of LRS, thereby inhibiting lysosomal localization of LRS and mTORC1 activity. It also effectively suppressed the activity of cancer-associated MTOR mutants and the growth of rapamycin-resistant cancer cells. These findings suggest new strategies for controlling tumor growth that avoid the resistance to existing mTOR inhibitors resulting from cancer-associated MTOR mutations.Leucyl-tRNA synthetase (LRS) is a leucine sensor of the mTORC1 pathway. Here, the authors identify inhibitors of the GTPase activating function of LRS, not affecting its catalytic activity, and demonstrate that the leucine sensor function of LRS can be a new target for mTORC1 inhibition.


Post-stroke memory impairment among patients with vascular mild cognitive impairment.
The American Stroke Association/American Heart Association recommended the criteria for diagnosis of vascular cognitive impairment and memory impairment (MI) is a feature in the classification of vascular mild cognitive impairment (VaMCI). VaMCI patients with MI may differ in terms of infarct location or demographic features, so we evaluated the clinical characteristics associated with MI in patients with VaMCI. A prospective multicenter study enrolled 353 acute ischemic stroke patients who underwent evaluation using the Korean Vascular Cognitive Impairment Harmonization Standard Neuropsychological Protocol at three months after onset. The association between MI and demographic features, stroke risk factors, and infarct location was assessed. VaMCI was diagnosed in 141 patients, and 58 (41.1%) exhibited MI. Proportions of men and of left side infarcts were higher in VaMCI with MI than those without (75.9 vs. 57.8%, P = 0.03, 66.7 vs. 47%, P = 0.02). Multiple logistic analyses revealed that male sex (odds ratio [OR] 3.07, 95% confidence interval [95% CI] 1.12-8.42), left-side infarcts (OR 3.14, 95% CI 1.37-7.20), and basal ganglia/internal capsule infarcts (OR 4.53, 95% CI 1.55-13.22) were associated with MI after adjusting other demographic variables, vascular risk factors, and subtypes of stroke. MI is associated with sex and infarct location in VaMCI patients.


Superflexible Artificial Soft Wood.
Soft woods have attracted enormous interest due to their anisotropic cellular microstructure and unique flexibility. The conventional wood-like materials are usually subject to the conflict between the superflexibility and robustness. Inspired by the synergistic compositions of soft suberin and rigid lignin of cork wood which has good flexibility and mechanical robustness, an artificial soft wood is reported by freeze-casting the soft-in-rigid (rubber-in-resin) emulsions, where the carboxy nitrile rubber confers softness and rigid melamine resin provides stiffness. The subsequent thermal curing induces micro-scale phase inversion and leads to a continuous soft phase strengthened by interspersed rigid ingredients. The unique configuration ensures crack resistance, structural robustness and superb flexibility, including wide-angle bending, twisting, and stretching abilities in various directions, as well as excellent fatigue resistance and high strength, overwhelming the natural soft wood and most wood-inspired materials. This superflexible artificial soft wood represents a promising substrate for bending-insensitive stress sensors.


Obstructive sleep apnea and diabetes mellitus.
There is convincing evidence that obstructive sleep apnea (OSA) is highly associated with impaired glucose metabolism. Analyze the prevalence of OSA in type 1 and type 2 diabetes mellitus (DM) patients. Evaluate the influence of OSA on glycemic control. The adult patients with diabetes mellitus (DM) followed in the department of internal medicine were referred to our Sleep Unit. A home respiratory polygraphy was then performed on all patients with body mass index (BMI) <40 kg/m(2). The glycemic control was assessed by the value of glycated hemoglobin (Hba1c) in the previous 3 months. A total of 46 patients were studied (20 men and 26 women), the mean age was 50±15 years and mean BMI was 28.6±4.9 kg/m(2). The mean Hba1c was 8.3±1.2. Twenty three patients had type 2 DM and 23 patients had type 1 DM. Twenty nine patients (63.0%) had OSA and 8.7% had severe OSA (AHI>30/h). The mean CT90 was 5.3±12.5 and the mean AHI was 13.6±18.3. The mean AHI was similar between type 1 and type 2 DM (15.7±24.5 Vs 11.6±8.9; p=0.46). The AHI was not correlated with the BMI. Type 2 DM patients with poor glycemic control (HbA1c>7.5%) had a significantly higher mean AHI (14.3±9.0 vs 6.4±6.2; p=0.038). This difference did not remain significant after adjustment for BMI (p=0.151). The prevalence of OSA in type 1 DM is similar to that found in type 2 DM. We note the high prevalence of OSA in younger patients with type 1 DM.


Quality-of-life trials in lung cancer: past achievements and future challenges.
Much work has been done regarding QOL in lung cancer trials. There are now several validated QOL instruments, particularly for patients with lung cancer. Past accomplishments include key trials demonstrating a benefit of chemotherapy or radiation in patients with advanced NSCLC not only regarding traditional endpoints but also by improving palliation and aspects of QOL such as pain and dyspnea. More recently, studies have emerged that incorporate QOL in patients with locally advanced disease. Key challenges relate to the optimal design and successful completion of these QOL studies. Missing data remains a key problem in many QOL studies, particularly in lung cancer trials. Future studies should focus on incorporating QOL into phase III studies with clear hypotheses that can ultimately lead to clinically meaningful interventions.


Primary Hepatitis A vaccination failure is a rare although possible event: results of a retrospective study.
A case of Hepatitis A occurred in a traveller in spite of a complete course of immunization with a combined HAV and HBV vaccine [Taliani G, Sbaragli S, Bartoloni A, Santini MG, Tozzi A, Paradisi F. Hepatitis A vaccine failure: how to treat the threat. Vaccine 2003;21(31):4505-6]. A retrospective study was performed to evaluate whether the failure was primary or could be attributed to a specific lot of vaccine or to its inadequate handling and/or storage. Two distinct populations of vaccinees were selected in a 1:2 proportion. The case group (N=31) included subjects who were vaccinated in the same period and with the same lot and batch of vaccine as the case. The control group (N=62) included subjects who received different lot and batch of the same vaccine as the case group. A persisting antibody response to HAV vaccine was found among all subjects (anti-HAV >20mIU/ml). The overall anti-HBs seropositivity rate (anti-HBs >10mIU/ml) was 74%, without significant difference between the case (77%) and the control group (73%; P>0.05). The reported Hepatitis A case can be attributed to a rare primary vaccine failure rather than to inefficacy of a specific lot of vaccine or to inappropriate vaccine handling or storage. Our study supports the indications for use of combined Hepatitis A+B immunization in travellers at risk for both infections, but stresses the need for information on correct hygienic behaviours while abroad.


Dynamic switching of the spin circulation in tapered magnetic nanodisks.
Magnetic vortices are characterized by the sense of in-plane magnetization circulation and by the polarity of the vortex core. With each having two possible states, there are four possible stable magnetization configurations that can be utilized for a multibit memory cell. Dynamic control of vortex core polarity has been demonstrated using both alternating and pulsed magnetic fields and currents. Here, we show controlled dynamic switching of spin circulation in vortices using nanosecond field pulses by imaging the process with full-field soft X-ray transmission microscopy. The dynamic reversal process is controlled by far-from-equilibrium gyrotropic precession of the vortex core, and the reversal is achieved at significantly reduced field amplitudes when compared with static switching. We further show that both the field pulse amplitude and duration required for efficient circulation reversal can be controlled by appropriate selection of the disk geometry.


Stress-induced morphohistochemical and functional changes in rat adrenal cortex, testis and major salivary glands.
The effect of repeated stress (1 h of daily immobilization for seven consecutive days) on the adrenal cortex of young adult male albino rats was evaluated by morphohistochemical methods and plasma assays; at the same time, testes and major salivary glands, as steroid-producing and -depending organs, respectively, were examined. Morphological and histochemical changes were found in the adrenal cortex, testis and submaxillary gland, though varying in degree and extent depending on the gland examined. Corticosterone and progesterone plasma levels increased, in agreement with the lipid depletion observed in the zona fasciculata, while testosterone and androstenedione decreased, as confirmed by the less marked enzymatic activity in the Leydig cells. The study thus proves that repeated stress, even of temporary duration, is able to influence directly or indirectly the morphofunctional state of the three examined glands, suggesting a functional linkage.


Sodium fluoroacetate toxicity: a case report of malicious poisoning in dogs across a Phoenix, Arizona neighborhood.
In May 2016, thirteen dogs housed in backyards within a single neighborhood were reported to have developed convulsions and died within a 24 h period. An investigation of the scene by law enforcement resulted in submission of eight dogs for postmortem examination. It was suspected that a rapid acting toxin was the cause of death. A gas chromatography-mass spectrophotometry (GC-MS) protocol combined with thin-layer chromatography that allows screening for common convulsants failed to identify a toxin in either pooled gastric content or liver samples from select cases. After consultation with a veterinary toxicologist, sodium fluoroacetate poisoning was investigated. Sodium fluoroacetate, also known as 1080, is a pesticide that was available in the United States from the 1940's to the 1970's, but since 1972 has been banned or under EPA restricted use. When gastric content was re-tested using a GC-MS protocol with selective fluoroacetate ion monitoring and carbon 14 radiolabeling to facilitate quantification, 379 ppb sodium fluoroacetate was detected in a pooled gastric content sample. In spite of its banned status, sodium fluoroacetate remains a rarely reported cause of malicious poisoning in domestic dogs in the United Sates. This compound is highly toxic and is capable of causing death in dogs, humans, other mammals, and insects in ingested quantities as small as a few droplets. Even when geographic or historical proximity to a source is not evident, this intoxication should be considered in dogs exhibiting compatible clinical signs.


Contrast-enhanced sonography of the renal transplant using triggered pulse-inversion imaging: preliminary results.
The purpose of our study was to quantify renal transplant parenchymal sonographic enhancement using pulse-inversion imaging (PII) and intermittent emission after contrast administration by means of bolus and infusion techniques, and to evaluate renal perfusion functional indices. A total of 34 patients, presenting with minor abnormalities (n = 14) and cortical perfusion changes due to parenchymal disorders (n = 12) or renal artery stenosis (n = 8) were included. Cardiac-triggered contrast-enhanced PII ultrasound (US) was performed after administration of SHU 508 A (Schering AG, Berlin, Germany), using a high mechanical index, a frame rate of one image every four cardiac cycles for bolus study, and a decreasing frame rate for infusion study. Compared to baseline values, peak enhancement ratio ranged from 5.6 to 14.7 using a bolus administration, and reached a value of 2.1 to 4.0 using infusion technique. Qualitative analysis showed heterogeneous enhancement in most allografts presenting with acute parenchymal disease (p = 0.03). In bolus studies, time to peak, wash-in and wash-out slopes increased in renal transplants with parenchymal disease and renal artery stenosis (p = 0.0001). Infusion administration exhibited no plateau in signal level, and no significant difference in enhancement ratio was found between groups of patients. Triggered PII after contrast agent administration provides morphologic and quantitative information about cortical vascularity in renal transplants.


Relationship between glomerular lesions, serum creatinine and interstitial volume in membrano-proliferative glomerulonephritis.
Morphometric investigations in 33 patients suffering from membranoproliferative glomerulonephritis at different grades of glomerular involvement showed that there is no certain relationship between the severity of glomerular lesions and the serum creatinine level. On the other hand there is a significant positive correlation between the relative interstitial volume and the level of serum creatinine. The best congruence (r=+0,87, p less than 0.0001) showed an exponential function y=0.563-e0.049x. We therefore conclude that in membranoproliferative glomerulonephritis which is generally considered to be a glomerular disease, interstitial changes have to be taken into account as a cause of renal insufficiency. Glomerular lesions alone cannot explain the functional impairment. The pathophysiologic factors concerning increased interstitial volume as a cause of renal insufficiency - probably immunologic in origin - are yet to be completely clarified.


Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children.
Probiotics and cranberry have been shown to inhibit Helicobacter pylori in vitro owing to bacteriocin production and high levels of proanthocyanidins, respectively. These effects have been confirmed in clinical trials with H. pylori-positive subjects. The aim of this study was to evaluate whether regular intake of cranberry juice and the probiotic Lactobacillus johnsonii La1 (La1) may result in an additive or synergistic inhibition of H. pylori in colonized children. A multicentric, randomized, controlled, double-blind trial was carried out in 295 asymptomatic children (6-16 y of age) who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1), cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1 (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for 3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo washout in those children who tested negative in the second UBT. Two hundred seventy-one children completed the treatment period (dropout 8.1%). Helicobacter pylori eradication rates significantly differed in the four groups: 1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB, and CB/La1 groups, respectively (P < 0.01); the latter group showed a slight but not significant increase when compared with the other treated groups. The third UBT was carried out only in 19 of the 38 children who tested negative in the second UBT and H. pylori was detected in 80% of them. These results suggest that regular intake of cranberry juice or La1 may be useful in the management of asymptomatic children colonized by H. pylori; however, no synergistic inhibitory effects on H. pylori colonization were observed when both foodstuffs were simultaneously consumed.


Transconjunctival entropion repair - the backdoor approach.
To present a modified transconjunctival approach for involutional entropion repair. This study is a retrospective consecutive single surgeon case series using a transconjunctival approach for involutional lower lid entropion (ILLE) repair. Eleven eyes were operated for involution entropion with 9 cases of complete resolution. Two patients required further Jones' retractor plication. Transconjunctival involutional lower lid entropion repair is a time-efficient, safe, and efficacious technique. The scar free technique described leads to full restoration of lower lid anatomy. In contrast to other reports we found a relatively low rate of recurrence on follow-up.


A proposal for producing calculated noise mapping defining the sound power levels of roads by street stratification.
The European Noise Directive proposes using strategic noise maps as tools to assess populations affected by environmental noise. It recommends using computational methods instead of in situ measurements when possible. A sound source's emission power is an important factor in the calculation of noise indicators. For traffic noise, this parameter is usually defined based on vehicle flow considering an emission spectrum that depends on the type of vehicle and its speed. This study analysed the possibility of using the categorisation method to propose an alternative method of defining a sound source's emission power to develop noise maps. This was accomplished using previously published values of the emission power per unit length. Another method is also proposed that estimates traffic flows. To verify their estimation capacity, the results of both methods were compared with the values obtained from in situ measurements. The results demonstrated similar uncertainties in both methods and were in the range of expected average uncertainties compared to the results obtained by calculating a noise map with the measured experimental values. In particular, for the differences between calculations and measurements, in absolute values, the mean uncertainties were approximately 2 dBA in estimating different long-term noise indicators. For the differences, the mean of the uncertainties obtained via the categorisation method did not present significant differences for the null value for all the analysed noise indicators. Street stratification is a rapid and low-cost approach for road traffic noise mapping without increasing uncertainties.


Development of sustained release matrix tablets of didanosine containing methacrylic and ethylcellulose polymers.
Didanosine, a nucleoside analog used in the treatment of acquired immuno deficiency syndrome (AIDS), has been incorporated into directly compressed monolythic matrices whose excipients were mixtures at different ratios of a methacrylic resin (Eudragit RSPM) and an ethylcellulose (Ethocel 100), both water-insoluble and pH-independent polymers. Technological characterization (drug particle morphology, mean weight, diameter, thickness and hardness of tablets) was carried out and in vitro drug release behaviour was measured using the USP basket apparatus. The effect of varying the Eudragit-Ethocel ratio, as well as the drug-polymeric matrix ratio, was evaluated. The results showed the suitability of Eudragit-Ethocel mixtures as matrix-forming material for didanosine sustained release formulations. Combination of the moderate swelling properties of Eudragit RSPM with the plastic properties of the more hydrophobic Ethocel 100 allowed suitable modulation of didanosine release.


The Impact of Wireless Network Mobile Devices on College Students' Labour Concept Education in Artificial Intelligence Environment.
To cultivate correct labour values and good labour quality of college students and effectively promote the development of their labour concept education, this work explores the impact of wireless network mobile devices on college students' labour concept education under the environment of artificial intelligence. Firstly, a questionnaire survey is used to investigate the labour concept of 400 college students. Secondly, the impact of wireless network mobile devices on college students' labour education is obtained by comparing group A (using artificial intelligence APPs for wireless network devices to learn about labour concepts) and group B (using traditional classroom teaching methods for to learn about labour concepts). According to the statistical survey results, about 20% of college students agree that "if they have enough money to live, they do not have to work"; while less than 50% agree that "they cannot be admitted to civil servants and senior managers in the company and are willing to engage in ordinary labour in the future". Meanwhile, about 50%-60% of college students think that "housework has nothing to do with me, and it's all the work of adults". In the question "What would you do when you find that the public area is dirty and poor, but it's not your turn to be on duty?", only about 50% of college students are willing to clean actively. Comparing the data of group A and group B suggests that the labour view expressed in group A is more biased in the cognition of labour purpose, and students in group A is more negative and lazier in labour attitude and labour habits, which shows that wireless network mobile devices have a great negative impact on the overall labour view of college students. Therefore, it is revealed in this work that the correct use of artificial intelligence technology in the education of labour concept has extremely important value for the intelligent development of education methods.


Discontinuation of primary prophylaxis against Mycobacterium avium complex infection in HIV-infected persons receiving antiretroviral therapy: observations from a large national cohort in the United States, 1992-2002.
In a large, diverse cohort of human immunodeficiency virus (HIV)-infected persons receiving routine care, the proportion of eligible persons who discontinued primary prophylaxis against Mycobacterium avium complex (MAC) infection, according to guidelines of the US Public Health Service and the Infectious Diseases Society of America, increased from 16.7% (in 1996) to 84.9% (in 2002). The discontinuation of primary prophylaxis was not associated with an increased risk of disseminated MAC infection.


Effect of mono- and diketone group in curcumin analogues on amyloid fibrillation of hen egg white lysozyme.
Curcumin has attracted more attention because of its inhibition efficacy on protein amyloid fibrillation. However, the inhibition mechanism was still ambiguous and the clinical application of curcumin was greatly limited because of its poor stability at physiological conditions for the presence of β-diketone moiety. In this paper, a new mono-ketone-containing curcumin analogue (MDHC) was designed and synthesized to realize the possible inhibition mechanism and unveil the important role of β-diketone moiety of curcumin in the inhibition process of amyloid fibrillation using hen egg white lysozyme (HEWL) as model protein. Although all experiment results (ThT, CR, ANS and TEM) showed that the inhibitory capacity of curcumin was better than MDHC, MDHC still could show obvious inhibition effect. Molecular docking showed that both curcumin and MDHC could bind with HEWL by hydrogen bond of phenloic hydroxyl and the binding energy of MDHC was higher than that of curcumin. All the findings inferred that β-diketone group was one of great important groups in the inhibition process of HEWL amyloid fibrillation, which provided more room to construct novel inhibition reagents.


Congenital hyperinsulinism: current trends in diagnosis and therapy.
Congenital hyperinsulinism (HI) is an inappropriate insulin secretion by the pancreatic β-cells secondary to various genetic disorders. The incidence is estimated at 1/50, 000 live births, but it may be as high as 1/2, 500 in countries with substantial consanguinity. Recurrent episodes of hyperinsulinemic hypoglycemia may expose to high risk of brain damage. Hypoglycemias are diagnosed because of seizures, a faint, or any other neurological symptom, in the neonatal period or later, usually within the first two years of life. After the neonatal period, the patient can present the typical clinical features of a hypoglycemia: pallor, sweat and tachycardia. HI is a heterogeneous disorder with two main clinically indistinguishable histopathological lesions: diffuse and focal. Atypical lesions are under characterization. Recessive ABCC8 mutations (encoding SUR1, subunit of a potassium channel) and, more rarely, recessive KCNJ11 (encoding Kir6.2, subunit of the same potassium channel) mutations, are responsible for most severe diazoxide-unresponsive HI. Focal HI, also diazoxide-unresponsive, is due to the combination of a paternally-inherited ABCC8 or KCNJ11 mutation and a paternal isodisomy of the 11p15 region, which is specific to the islets cells within the focal lesion. Genetics and 18F-fluoro-L-DOPA positron emission tomography (PET) help to diagnose diffuse or focal forms of HI. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damage. This includes a glucose load and/or a glucagon injection, at the time of hypoglycemia, to correct it. Then a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. When medical and dietary therapies are ineffective, or when a focal HI is suspected, surgical treatment is required. Focal HI may be definitively cured when the partial pancreatectomy removes the whole lesion. By contrast, the long-term outcome of diffuse HI after subtotal pancreatectomy is characterized by a high risk of diabetes, but the time of its onset is hardly predictable.


A case report of Extranodal natural killer / T-cell lymphoma presenting as extensive myiasis.
We described a 56-year-old Indonesian man with one-month history of nasal obstruction and rapidly increasing nasal swelling and two weeks history of severe facial pain with foul smelling discharge, bleeding and noticing live maggots emerging from his nasal and oral cavity. On examination, he appeared cachexic with a markedly swollen, erythematous and deformed external nose. Live maggots, pus and necrotic tissues were found in both nasal cavities, with erosion of upper gingiva and hard palate. Patient was managed initially with tracheostomy under local anaesthesia, followed by removal of around 350 live maggots from the nasal cavities and debridement of necrotic tissues. A midline nasal cavity mass which extended laterally into the nasal cavity was found, along with a large defect over the gingival labial sulcus with necrotic hard palate and a communication between oral and nasal cavities. Biopsies were taken from the nasal mass, gingiva and hard palate. Histopathological results from the biopsies showed diffuse, aggressive infiltrative malignant lymphoid cells with widespread angionecrosis, consistent with features of extranodal NK/T-cell lymphoma. To our knowledge, there is only one other reported case where the diagnosis of ENKTCL was made after patient presented with oro-nasal myiasis. Clinicians should have raised awareness on this atypical presentation so that further investigation and management can be implemented promptly.


The tetramethoxyflavone zapotin selectively activates protein kinase C epsilon, leading to its down-modulation accompanied by Bcl-2, c-Jun and c-Fos decrease.
Zapotin, a tetramethoxyflavone, is a natural compound with a wide spectrum of activities in neoplastic cells. Protein kinase C epsilon (PKCε) has been shown to be oncogenic, with the ability to increase cell migration, invasion and survival of tumor cells. Here we report that zapotin inhibits cell proliferation. In wild-type HeLa cells with basal endogenous expression of PKCε, the IC(50) was found to be 17.9 ± 1.6 μM. In HeLa cells overexpressing doxycycline-inducible constitutively active PKCε (HeLaPKCεA/E), the IC(50) was 7.6 ± 1.3 μM, suggesting that PKCε enhances the anti-proliferative effect of zapotin. Moreover, we found that zapotin selectively activated PKCε in comparison with other PKC family members, but attenuated doxycycline-induced PKCε expression. As a result of zapotin treatment for 6, 12 and 24h, the doxycycline-induced levels of the two differently phosphorylated PKCε forms (87 kDa and 95 kDa) were decreased. Migration assays revealed that increasing concentrations of zapotin (from 3.5 to 15 μM) decreased migration of HeLaPKCεA/E cells. Furthermore, zapotin significantly increased the fraction of apoptotic cells in doxycycline-induced (HeLaPKCεA/E) cells after 24h and decreased the levels of Bcl-2, c-Jun, c-Fos. This was accompanied by a degradation of PARP-1. In summary, activation of PKCε and down-modulation of the induced PKCε level by zapotin were associated with decreased migration and increased apoptosis. These observations are consistent with the previously reported chemopreventive and chemotherapeutic action of zapotin.


Massive pulmonary embolism: percutaneous emergency treatment by pigtail rotation catheter.
This study was designed to assess the feasibility, efficacy and safety of mechanical fragmentation of pulmonary emboli using a new rotational pigtail catheter system. Acute massive pulmonary embolism associated with right ventricular dysfunction is frequently lethal, despite high-dose thrombolytic therapy. Adjunctive catheter fragmentation may prevent a fatal outcome. In 20 patients (age 58.9+/-10.5 years) with severe hemodynamic impairment, massive pulmonary emboli were fragmented by mechanical action of the rotating pigtail. Fifteen patients received thrombolysis after embolus fragmentation or no thrombolysis at all (noninterference group). Prefragmentation pulmonary arterial occlusion was 68.6 +/- 11.3% for both lungs. Pulmonary placement and navigation of the fragmentation catheter was easy and rapid. Fragmentation time was 17+/-8 min. The noninterference group showed a decrease pre- to postfragmentation of shock index from 1.28+/-0.53 to 0.95+/-0.38 (p = 0.011), mean pulmonary artery pressure from 31+/-5.7 to 28+/-7.5 mm Hg (p = 0.02) and a recanalization by fragmentation of 32.9+/-11.8% (mean angiographic score per treated lung from 7.4 to 5.0). Overall mortality was 20%. Fragmentation by pigtail rotation catheter provided for a rapid and safe improvement of the hemodynamic situation and an average recanalization of about one-third of the pulmonary embolic occlusion. The method appears useful especially in high-risk patients threatened by right ventricular failure, to accelerate thrombolysis, and as a minimal-invasive alternative to surgical embolectomy.


Sinusoidal fetal heart rate.
Two cases with sinusoidal fetal heart rates (SHR) with good perinatal outcome are reported. Since nonstress tests, oxytocin challenge tests and serum free estriols were normal, SHR was considered not indicative of fetal compromise. A SHR can occasionally be found in connection with reactive nonstress test. In those cases it may be of minor importance when compared to the situations when the tracing also shows a nonreactive nonstress test and the perinatal outcome is often poor.


The quality of research on physical examination for abdominal aortic aneurysm.
A review of nursing literature revealed no studies regarding physical examination or other interventions (except unit based) for abdominal aortic aneurysms (AAA). The physician literature was explored, revealing an excellent meta-analysis in 1999 of studies before that date with regard to physician accuracy in physical examination for AAA. These are reviewed for quality and recommendations made for nursing research and the role of the Society for Vascular Nursing in teaching nurses.


Inflammation and pregnancy: the role of toll-like receptors in trophoblast-immune interaction.
During normal pregnancy, the decidua is populated by a variety of leucocytes; however, cells of the innate immune system seem to dominate this tissue. Their presence suggests that the innate immune system is not indifferent to the fetus and has been associated with a response of the maternal immune system to the "semi-allograft fetus." New evidences, however, indicates that these immune cells are critical for decidual and trophoblast development, rather than induction of tolerance. We hypothesized that, during implantation, an inflammatory environment is necessary for the attachment and invasion of the blastocyst. Therefore, we propose the existence of an "inflammatory-mediated embryo implantation" condition that is dependent on the proper "education" of the innate immune system by the trophoblast. Here we postulate that trophoblast cells successfully orchestrate their inflammatory environment and regulate immune cell differentiation and activation.


Simulated car driving and its association with cognitive abilities in patients with schizophrenia.
Patients with schizophrenia commonly suffer from impairments in various aspects of cognition. These deficits were shown to have detrimental effects on daily life functioning and might also impair car driving. This study is the first to examine driving behaviour of patients with schizophrenia using an advanced driving simulator, and to explore the role of cognitive abilities of people with schizophrenia for driving. Non-acute patients with schizophrenia (n = 31) and healthy comparison participants (n = 31) performed a comprehensive neuropsychological assessment and driving simulator rides. Neuropsychological and driving performances were compared between groups. Moreover, associations were explored between cognitive functions and driving behaviour in the entire group. Patients with schizophrenia revealed impairments in multiple aspects of cognition. In the driving simulator, patients with schizophrenia showed no indication of deviant driving in terms of number of collisions or reacting to critical situations, and even showed better lane control compared to healthy individuals. However, patients with schizophrenia drove significantly slower than healthy individuals, and caused more hindrance to the car behind while merging on the motorway. Slower driving was associated with lower test scores on attention and processing speed. Hindering the car behind was associated with test performance on planning and inhibition. It is concluded that driving of patients with schizophrenia is characterized by a relatively slow speed, and can also be impaired in certain aspects, i.e. hindering a car behind while merging. Cognitive functions are crucial for driving, and should be target of treatment.


Rare Case of Tracheal Fibromyxoma in Obstructive Tracheal Mass.
A 77-year-old male with a history of chronic obstructive pulmonary disease (COPD) who presented with cough, congestion, and stridor and was found to have a near obstructing tracheal mass. He subsequently underwent excision of the mass. On pathologic examination, it was diagnosed as fibromyxoma of the trachea. Primary tumors of the trachea are rare, and fibromyxoma of the trachea is extremely rare. This is the third report of a fibromyxoma on the tracheal wall. In this report the clinical manifestations, and surgical management were compared with the other two reported cases.


Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery.
PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ~100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery.


Unexpected effects of trace impurities on the properties of polymer-stabilized ruthenium colloids from different sources of ruthenium(III) chloride hydrate.
The stability and the catalytic performances of polyvinylpyrrolidone-stabilized ruthenium colloids (PVP-Ru) prepared by using RuCl(3).xH(2)O of different sources have been investigated. The trace impurity content of platinum and palladium in RuCl(3).xH(2)O was demonstrated to be the main factors affecting the properties of PVP-Ru colloids.


A method of treating post-irradiation rectovaginal fistulas.
A sphincter-saving operative method of treating post-irradiation rectovaginal fistulas is presented. The technique involves the peranal anastomosis of healthy colon to the mid-anal canal using a 'sleeve' anastomosis. Four patients have been treated with cure of the fistula and a return to normal bowel habit. A fifth, with an irradiation ulcer causing intractable pain, also obtained complete relief of symptoms.


Thermal windows and metabolic performance curves in a developing Antarctic fish.
For ectotherms, temperature modifies the rate of physiological function across a temperature tolerance window depending on thermal history, ontogeny, and evolutionary history. Some adult Antarctic fishes, with comparatively narrow thermal windows, exhibit thermal plasticity in standard metabolic rate; however, little is known about the shape or breadth of thermal performance curves of earlier life stages of Antarctic fishes. We tested the effects of acute warming (- 1 to 8 °C) and temperature acclimation (2 weeks at - 1, 2, 4 °C) on survival and standard metabolic rate in early embryos of the dragonfish Gymnodraco acuticeps from McMurdo Sound, Ross Island, Antarctica. Contrary to predictions, embryos acclimated to warmer temperatures did not experience greater mortality and nearly all embryos survived acute warming to 8 °C. Metabolic performance curve height and shape were both significantly altered after 2 weeks of development at - 1 °C, with further increase in curve height, but not alteration of shape, with warm temperature acclimation. Overall metabolic rate temperature sensitivity (Q 10) from - 1 to 8 °C varied from 2.6 to 3.6, with the greatest thermal sensitivity exhibited by embryos at earlier developmental stages. Interclutch variation in metabolic rates, mass, and development of simultaneously collected embryos was also documented. Taken together, metabolic performance curves provide insight into the costs of early development under warming temperatures, with the potential for thermal sensitivity to be modified by dragonfish phenology and magnitude of seasonal changes in temperature.


Brain neurotransmitter receptors in Friedreich's ataxia.
The binding of 3H-quinuclidinyl benzilate, a muscarinic cholinergic antagonist, of 3H-dihydroalprenolol, a beta adrenergic antagonist, and of 3H-flunitrazepam, a ligand which labels benzodiazepine receptors, was examined in several regions of control and Friedreich's ataxia (FA) brains. 3H-Quinuclidinyl benzilate binding appeared to increase in the inferior olivory nucleus, anterior and posterior cerebellar vermi but was unaltered in the dentate nucleus and cerebellar hemisphere of FA brain. The binding of 3H-dihydroalprenolol seemed to increase in the inferior olivary nucleus yet was not different from controls in the dentate nucleus, cerebellar hemisphere, anterior and posterior cerebellar vermi of FA brains. 3H-Flunitrazepam binding was slightly lowered in the inferior olivary and dentate nuclei but was unchanged in the other FA brain regions examined. The present study suggests possible trends in neurotransmitter receptor alterations in post-mortem brain tissue of FA patients.


[The characteristics of the minute fluctuations in haloperidol-induced catalepsy and the contribution of different sections of the striatum to their formation in rats].
After constant recording of haloperidol catalepsy in rats a rhythmic structure with waves of minute range was observed. On the basis of individual pharmacological sensitivity all rats may be divided in animals with strong rhythmic fluctuations but rapid tolerance (hyperkinetic type) and with weak rhythmicity but delayed adaptation to haloperidol (hypokinetic type). Oscillatory pattern of catalepsy increased after bilateral lesions of dorsal striatum and decreased after ventral striatectomy. As suggested, ventral striatum has a rhythmogenic function which conditions a more easy neuroleptic tolerance.


Mode of action hypothesis testing in chemical safety assessments using metabolomics as supporting evidence: Phenobarbital and cyclobutrifluram metabolomics profile comparison.
In long term rodent studies administering Cyclobutrifluram (TYMIRIUM® Technology), a new agrochemical, there was a slight elevation of incidence of hepatocellular carcinomas in male CD-1 mice that was within the historical control range but appeared to be dose responsive. Cyclobutrifluram's ability to activate mouse constitutive androstane receptor (CAR) mediated gene transcription was confirmed in vitro, therefore a 28-day dietary toxicity study was conducted in vivo in male CD-1 mice to assess the CAR activation mode of action hypothesis of Cyclobutrifluram along with phenobarbital, a known CAR activator. In addition to other end points comprehensive (polar and lipidomic) hybrid metabolomics analyses were performed on terminal plasma and liver samples following 2-, 7- and 28-days dietary exposure to cyclobutrifluram and phenobarbital. The data generation and quality assessments were performed in line with the principles of the MEtabolomics standaRds Initiative in Toxicology (MERIT).First the full annotated feature set was used to compare the metabolomic changes induced by the administration of the two test substances using Shared and Unique Structures plots. This gave a comprehensive overview of the similarity of the two effect profiles showing good correlation and demonstrated that no other, alternative effect signatures were detected. Then the phenobarbital induced differentially abundant metabolites were selected, compared to the literature and their direction of change was assessed in cyclobutrifluram profiles, finding good agreement. Both approaches concluded that the metabolomics data supports the CAR activation hypothesis. Comparison of the metabolomic effect profiles can be a line of evidence in mode of action hypothesis testing in the chemical risk assessment process.


Emerging parasites and vectors in a rapidly changing world: from ecology to management.
Global changes have influenced our societies in several ways with both positive (e.g., technology, transportation, and food security), and negative impacts (e.g., mental health problems, spread of diseases, and pandemics). Overall, these changes have affected the distribution patterns of parasites and arthropod vectors with the introduction and spreading of alien species in new geographical areas, eventually posing new challenges in public health. In this framework, the Acta Tropica Special Issue "Emerging parasites and vectors in a rapidly changing world: from ecology to management" provides a focus on the biology, ecology and management of emerging parasites and vectors of human and veterinary importance. Herein we review and discuss novel studies dealing with interactions of parasites and vectors with animals in changing environmental settings. In our opinion, a special focus on the implementation of management strategies of parasitic diseases to face anthropogenic environmental changes still represent a priority for public health. In the final section, key research challenges in this rapidly changing scenario are outlined.


Correlation between body mass index and efficacy of anti-PD-1 inhibitor in patients with non-small cell lung cancer.
High body mass index (BMI) has been reported to be associated with the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC), but the association between BMI and efficacy of anti-PD-1 inhibitors remains controversial. The present study investigated this association in patients with advanced NSCLC. We retrospectively reviewed patients with advanced NSCLC who received PD-1 inhibitors at the National Cancer Center Hospital between January 2016 and December 2018. The efficacy of PD-1 inhibitors (progression-free survival [PFS], overall survival [OS], and response rate) was compared between overweight (BMI ≥25 kg/m2) and non-overweight (BMI <25 kg/m2) groups. Cohort 1 included patients with high PD-L1 expression who were treated with pembrolizumab as first-line therapy; Cohort 2 included patients treated with nivolumab/pembrolizumab as second- or later-line treatment. A total of 324 patients were included in this study and the median BMI (IQR) was 21.4 (19.5-23.6) kg/m2. Of the 324 patients, 279 (86.1%) and 45 (13.9%) were in the non-overweight and overweight groups, respectively. No significant differences in objective response rate (ORR), PFS, or OS were found between overweight and non-overweight patients overall (n = 324; overweight vs. non-overweight: ORR, 28.9% vs. 31.9%, respectively [p = 0.68]; PFS, 7.6 vs. 5.8 months, respectively [p = 0.43]; and OS, 17.6 vs. 15.3 months, respectively [p = 0.90]), or between overweight and non-overweight patients in Cohorts 1 and 2. No significant differences in the efficacy of PD-1 inhibitors were observed between overweight and non-overweight patients.


2.7 μm emission properties of Er3+ doped tungsten-tellurite glass sensitized by Yb3+ ions.
With a 980 nm laser diode (LD) pumped, the sensitized effect of Yb(3+) ions on 2.7 μm emission properties and energy transfer mechanism in Yb(3+)/Er(3+) co-doped tungsten-tellurite glass were investigated in present paper. Based on absorption spectra, Judd-Ofelt parameters and radiative transition probabilities were calculated and analyzed. The emission spectra were tested and the optimized concentration ratio of Yb(3+) to Er(3+) ions was found to be 3:0.5 with a largest calculated emission cross-section (6.05×10(-21) cm(2)) corresponding to Er(3+):(4)I11/2→(4)I13/2 transition. When the concentration ratio of Yb(3+) to Er(3+) ions was 4:0.5, 1.5 μm and 2.7 μm emission decreased while up-conversion increased. The decreased 1.5 μm and 2.7 μm emission were induced by the saturation of Er(3+):(4)I13/2 level. In brief, the advantageous spectroscopic characteristics indicated that Yb(3+)/Er(3+) co-doped tungsten-tellurite glass may be a promising candidate for application of 2.7 μm emission.


Surgical treatment of infantile subglottic hemangioma.
Three cases of infantile subglottic hemangioma are described. Generally conservative management is favored by most authors. These present lesions were removed surgically by midline cricotracheotomy. Follow-up showed that all children were well and without complaints. The authors believe that besides management with the CO2 laser and short-term steroid therapy, operative treatment of infantile subglottic hemangioma is a valuable alternative which should receive more attention. All children were decannulated a few days after surgery.


Integrated photonic emitter with a wide switching range of orbital angular momentum modes.
Due to the nature of infinite dimensionality, the orbital angular momentum (OAM) has been considered as a new degree of freedom of light and widely expanded the scopes of substantial optical applications such as optical telecommunication, quantum information, particle manipulation and imaging. In recent years, the integrated photonic OAM emitters have been actively investigated due to both compactness and tunability. Essentially, the number of available OAM modes by dynamic switching should be large enough so that the dimensionality of OAM could be explored as much as possible. In this work, an integrated photonic emitter with a wide switching range of OAM modes is theoretically developed, numerically simulated, and experimentally verified. The independence of the micro-ring cavity and the scattering unit provides the flexibility to design the device and optimize the performance. Specifically, the dynamic switching of nine OAM modes (l = -4 ~ 4) with azimuthal polarization has been demonstrated by electrically controlled thermo-optic effect.


Autism spectrum disorders--are they really epidemic?
The aim of this paper is to report on how different external methodological factors influence estimates of ASD prevalence. PubMed searches was conducted using the search terms, "Autism", "Autistic Disorder", "Autism Spectrum Disorders", "Asperger", "Prevalence" and "epidemiology", in combination. In total 49 studies were included. We also performed a manual search for and reviewed related articles referenced in the original articles. The reported prevalence rates of ASD vary widely, and so do the methodology used in the studies. There are reasons to argue that the methods used in some studies cause the high prevalence rates reported recently.


Incidence, Size and Orientation of Maxillary Sinus Septa-A Retrospective Clinical Study.
The purpose of this study is to analyze if there is any statistical correlation between the surgery's complexity (easy to difficult-depending on the anatomical conditions) and the patient's sex, type of edentulism, and left or right side of the maxilla. Cone beam computed tomography records of 1192 maxillary sinuses were evaluated, measured, and statistically analyzed with respect to patient sex, type of edentulism, and left or right side, taking into consideration Wen's proposed sinus septum classification. Our research suggests that most sinus augmentation procedures in patients presenting antral septum fall into the Moderate A category (31.94%) and that there is not a correlation between the surgery's complexity (easy to difficult) and the patient's sex, type of edentulism and left or right side of the maxilla. We suggest a minor modification to Wen's classification in view of the fact that our findings revealed a combination of medio-lateral and antero-posterior septa that we could not classify in one of the existing categories.


Insider information: what viruses tell us about endocytosis.
Viruses have long served as tools in molecular and cellular biology to study a variety of complex cellular processes. Currently, there is a revived interest in virus entry into animal cells because it is evident that incoming viruses make use of numerous endocytic pathways that are otherwise difficult to study. Besides the classical clathrin-mediated uptake route, viruses use caveolae-mediated endocytosis, lipid-raft-mediated endocytic pathways, and macropinocytosis. Some of these are subject to regulation, involve novel endocytic organelles, and some of them connect organelles that were previously not known to communicate by membrane traffic.


Fenretinide favorably affects mucins (MUC5AC/MUC5B) and fatty acid imbalance in a manner mimicking CFTR-induced correction.
Cystic fibrosis (CF) is the most common genetic disease in Caucasians. CF is manifested by abnormal accumulation of mucus in the lungs, which serves as fertile ground for the growth of microorganisms leading to recurrent infections and ultimately, lung failure. Mucus in CF patients consists of DNA from dead neutrophils as well as mucins produced by goblet cells. MUC5AC mucin leads to pathological plugging of the airways whereas MUC5B has a protective role against bacterial infection. Therefore, decreasing the level of MUC5AC while maintaining MUC5B intact would in principle be a desirable mucoregulatory treatment outcome. Fenretinide prevented the lipopolysaccharide-induced increase of MUC5AC gene expression, without affecting the level of MUC5B, in a lung goblet cell line. Additionally, fenretinide treatment reversed the pro-inflammatory imbalance of fatty acids by increasing docosahexaenoic acid and decreasing the levels of arachidonic acid in a lung epithelial cell line and primary leukocytes derived from CF patients. Furthermore, for the first time we also demonstrate the effect of fenretinide on multiple unsaturated fatty acids, as well as differential effects on the levels of long- compared to very-long-chain saturated fatty acids which are important substrates of complex phospholipids. Finally, we demonstrate that pre-treating mice with fenretinide in a chronic model of P. aeruginosa lung infection efficiently decreases the accumulation of mucus. These findings suggest that fenretinide may offer a new approach to therapeutic modulation of pathological mucus production in CF.


Predicting Dengue Outbreaks in Cambodia.
In Cambodia, dengue outbreaks occur each rainy season (May-October) but vary in magnitude. Using national surveillance data, we designed a tool that can predict 90% of the variance in peak magnitude by April, when typically <10% of dengue cases have been reported. This prediction may help hospitals anticipate excess patients.


Seronegative arthropathies in the foot.
It has been seen that involvement of the foot in the seronegative arthropathies forms a regular and varied part of the clinical picture. This is often quite different from that seen in rheumatoid arthritis; its components, whether in joints, periarticular structures, or as surface manifestations, may be characteristic enough to raise the diagnosis of 'spondarthritis'. The features described, though characteristic of the spondarthritides, are, however, not pathognomonic. Thus, the osteolysis in psoriatic arthritis also occurs in neuropathic arthritis (e.g. syringomyelia, leprosy), psoriatic periosteal changes may mimic osteosarcomatous proliferations, and the calcaneal enthesitis so typical of spondylitis, Reiter's disease and psoriatic arthritis, may also be seen in metabolic arthropathies. It should also be mentioned here that the severe erosive osteolytic changes leading to psoriatic arthritis mutilans may also be seen, albeit rarely, in rheumatoid arthritis. Ankylosis, too, is not totally confined to the spondarthritides, having also been reported in occasional patients with rheumatoid arthritis. Calcaneal erosions, sometimes envisaged as a spondarthritic feature, also occur in rheumatoid patients. Within the spondarthritis matrix, a striking overlap is seen in the pattern of arthritis. Thus, involvement of the feet in psoriatic arthritis and in Reiter's disease shows many similarities, particularly the tendency to involve IP joints in asymmetrical oligoarticular fashion. In the hindfoot, too, parallels can be drawn between the tendency to Achilles and plantar insertion enthesitis in ankylosing spondylitis and Reiter's disease. On the other hand, the arthropathies of the chronic inflammatory bowel diseases, ulcerative colitis, Crohn's disease, and Whipple's disease, share with Behçet's syndrome an asymmetrical involvement of knees and ankles, but relative freedom from foot involvement. Regarding the surface features in the foot of spondarthritides, there is overlap here, too. For example, the nail dystrophy of psoriasis can be indistinguishable from that of Reiter's disease, and pustular psoriasis in its severe form cannot be differentiated from keratoderma blenorrhagica, even at the histological level. Other surface manifestations affecting the lower limb in general distribution may spread to the feet and thus fall within the ambit of this discussion. Such features include the lesions of erythema nodosum, patches of pyoderma gangrenosum, and the tender cords of thrombophlebitis, all of which have a higher prevalence in seronegative arthritis than in seropositive disease.(ABSTRACT TRUNCATED AT 400 WORDS)


The effect of phosphate on the unfolding-refolding of phosphoglycerate kinase induced by guanidine hydrochloride.
Phosphate ions were found to stabilize the native structure of phosphoglycerate kinase without modifying the folding pathway. The transition curves obtained from different signals: enzyme activity, ellipticity at 220 nm and fluorescence intensity at 336 nm (excitation at 292 nm) are shifted to smaller guanidine hydrochloride cm values in the absence of phosphate. The kinetic characteristics are qualitatively similar, unfolding rate constants being slightly smaller in the presence of phosphate. The mechanism by which the native structure of phosphoglycerate kinase is stabilized by phosphate probably occurs upon specific phosphate binding to the nucleotide beta- or gamma-phosphate binding site of nucleotides.


Visceral myopathy of the gastrointestinal and genitourinary tracts in infants.
We describe 4 infants who had chronic intestinal pseudoobstruction caused by visceral myopathy. Three of the 4 were girls. Two were symptomatic at birth and 2 were symptomatic by 3 wk of age. All had abdominal distention and emaciation, 3 of the 4 had severe obstipation and fecal impactions, and 3 had signs of urologic obstruction. All had gaseous distention of the small bowel and colon, and barium studies showed dilated small bowel and colon, with slow transport through the small intestine. Two of 3 had enlarged stomachs and slowed gastric emptying, and 3 had dilated bladders and ureters. The 1 infant studied by esophageal manometry had absence of esophageal contractions. Despite total parenteral nutrition in 3, all died within 10-18 mo. The pathologic features of visceral myopathy were identified in variable sample sites from the esophagus, stomach, small intestine, colon, bladder, and ureter of the 4 infants. Of 170 family members related to 3 of the infants, there was no consanguinity and no one appeared to be clinically affected. Thus, an infantile form of visceral myopathy exists which, pathologically, is identical to the familial and sporadic forms of visceral myopathy previously identified in adolescents and adults.


The effect of pedicle screw redirection after lateral wall breach--a biomechanical study using human lumbar vertebrae.
Currently, pedicle screw segmental fixation of the spine is considered a standard of care for a number of conditions. Most surgeons employ a free-hand technique using various intraoperative modalities to improve pedicle screw accuracy. Despite continued improvements in technique, pedicle breach remains a frequent occurrence. Once a breach is detected intraoperatively, the most common corrective maneuver is to medially redirect the pedicle screw into the pedicle. To our knowledge, the biomechanical impact of medially redirecting a pedicle screw after a lateral pedicle breach has not been examined. To compare the fixation strength of perfectly placed pedicle screws to the fixation strength of pedicle screws that were correctly placed after having been redirected (RD) following a lateral pedicle breach. A biomechanical study using human lumbar vertebrae. Ten fresh human lumbar vertebrae were isolated from five donors. Each vertebra was instrumented with a monoaxial pedicle screw into each pedicle using two different techniques. On one side, a perfect center-center (CC) screw path was created using direct visualization and fluoroscopy. A 6.0-mm-diameter cannulated tap and a pedicle probe were used to develop the pedicle for the 7.0-mm-diameter by 45-mm-long cannulated pedicle screw, which was placed using a digital torque driver. On the contralateral side, an intentional lateral pedicle wall breach was created at the pedicle-vertebral body junction using a guide wire, a 6.0-mm-diameter cannulated tap, and a pedicle probe. This path was then redirected into a CC position, developed, and instrumented with a 7.0-mm-diameter by 45-mm-long cannulated pedicle screw: the RD screw. For each pedicle screw, we assessed four outcome measures: maximal torque, seating torque, screw loosening, and post-loosening axial pullout. Screw loosening and axial pullout were assessed using an MTS machine. The biomechanical cost of a lateral pedicle breach and the requirement to redirect the pedicle screw are as follows: an overall drop of 28% (p<.002) in maximal insertion torque and 25% (p<.049) in seating torque, a drop of 25% (p<.040) in resistance to screw loosening, and a drop in axial pullout force of 11% (p<.047). Compared with a CC lumbar pedicle screw, an RD lumbar pedicle screw placed after a lateral wall breach is significantly weaker in terms of maximal insertional torque, seating torque, screw loosening force, and axial pullout strength. These significant decreases in biomechanical properties are clearly important when RD pedicle screws are placed at the cephalad or caudal end of a long construct. In this situation, augmentation of the RD screw is an option.


Translational profiling identifies a cascade of damage initiated in motor neurons and spreading to glia in mutant SOD1-mediated ALS.
Ubiquitous expression of amyotrophic lateral sclerosis (ALS)-causing mutations in superoxide dismutase 1 (SOD1) provokes noncell autonomous paralytic disease. By combining ribosome affinity purification and high-throughput sequencing, a cascade of mutant SOD1-dependent, cell type-specific changes are now identified. Initial mutant-dependent damage is restricted to motor neurons and includes synapse and metabolic abnormalities, endoplasmic reticulum (ER) stress, and selective activation of the PRKR-like ER kinase (PERK) arm of the unfolded protein response. PERK activation correlates with what we identify as a naturally low level of ER chaperones in motor neurons. Early changes in astrocytes occur in genes that are involved in inflammation and metabolism and are targets of the peroxisome proliferator-activated receptor and liver X receptor transcription factors. Dysregulation of myelination and lipid signaling pathways and activation of ETS transcription factors occur in oligodendrocytes only after disease initiation. Thus, pathogenesis involves a temporal cascade of cell type-selective damage initiating in motor neurons, with subsequent damage within glia driving disease propagation.


Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study.
The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles were observed. Blood and urine routine test, liver function, electrocardiogram, chest radiography and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155) and CA199, were assayed before and 1, 2, 4 and 6 years after MSCs transplantation. All the patients completed two times of MSCs infusions. One patient had mild dizzy and warm sensation 5 min after MSCs infusion, and the symptoms disappeared quickly. No other adverse event, including fluster, headache, nausea or vomit, was observed. There was no change in peripheral white blood cell count, red blood cell count and platelet number in these patients after followed up for 6 years. Liver functional analysis showed that serum alanine aminotransferase, glutamic-oxalacetic transaminase, total bilirubin and direct bilirubin remained in normal range after MSCs infusions. No newly onset abnormality was detected on electrocardiogram and chest radiography. Moreover, we found no rise of serum tumor markers, including AFP, CEA, CA125 and CA199, before and 6 years after MSCs infusions. Our long-term observational study demonstrated a good safety profile of allogeneic UC MSCs in SLE patients.


Tissue plasminogen activator-associated lingual artery hemorrhage.
Reported is the case of a patient with vertebrobasilar artery ischemia who received tissue plasminogen activator with resulting hemorrhage into the tongue and nearly exsanguinating hemorrhage from a branch of the lingual artery. Suggestions for immediate management of the hemorrhage as well as prevention are presented. As the use of thrombolytic agents increases and the list of their indications expands, unusual life-threatening hemorrhagic problems other than gastrointestinal or intracranial bleeding will be seen, and management decisions may be life saving.