Liquid disinfecting and sterilizing reprocessors used for flexible endoscopes.
In this issue, we evaluate three liquid disinfecting flexible endoscope reprocessors that can be used with a user-supplied liquid chemical germicide (LCG), primarily for high-level disinfection (HLD). Applying most of the same criteria and test methods, we also evaluated a fourth unit, presented separately, that is marketed as a liquid sterilizing reprocessor and must be used with manufacturer-supplied, single-use containers of LCG. Although the sterilizing unit can be used for rigid endoscopes, surgical instruments, and endoscopic accessories, we evaluated its application to the reprocessing of only flexible endoscopes. Our ratings are based on the following: (1) basic performance, such as compatibility with several different types of endoscopes and LCGs, inclusion of all essential reprocessing phases, and exposure of all endoscope surfaces to the LCG and rinse water; (2) safety, such as ensuring that essential reprocessing phases cannot be skipped or omitted, that personnel exposure to LCG vapors is minimized, and that the reprocessor is unlikely to contaminate the endoscope during reprocessing; and (3) human factors design, such as ease of use and installation. We did not perform microbiological testing to confirm HLD or sterilization by any of the evaluated reprocessors because, with a suitably clean endoscope that is in good condition, no evidence indicates that the LCGs used would not be effective on the surfaces that they contact; also, the results would be unique to the two flexible endoscopes that we used for our testing. We rated all four reprocessors Conditionally Acceptable. The units are Acceptable on the condition that users understand that they cannot be used to process the elevator cable channel of side-viewing duodenoscopes; additional conditions apply only to the liquid disinfecting units. However, if the conditions are met, all four units reduce the likelihood of using a contaminated endoscope on a patient and reduce personnel exposure to the LCG. Selection of a unit will be based on the needs and preferences of the individual healthcare facility. Our ratings also assume that these units will be used according to the manufacturers' instructions and the endoscope's operator's manual. Note that, although the evaluated liquid disinfecting units provide detergent-flushing, post-detergent water-rinse, and post-detergent water-rinse-removal phases, manual cleaning of endoscopes before automatic reprocessing is essential, regardless of which reprocessor is used.(ABSTRACT TRUNCATED AT 400 WORDS)


Spectrum of invasive Haemophilus influenzae type b disease in adults.
A prospective nationwide surveillance of invasive Haemophilus influenzae type b disease among adults (greater than or equal to 16 years old) was conducted in Finland during 1985 through 1988. Thirty-one cases were identified (annual incidence, 0.22/100,000). Of these infections, 71% occurred in patients with severe underlying conditions. The overall case fatality rate was 26%. Septicemia (13 patients) and pneumonia (seven patients) were the most common clinical manifestations of H influenzae type b infection; the others were epiglottitis (six patients), meningitis (three patients), and arthritis (two patients). Epiglottitis occurred in significantly younger patients, all of whom were women and four of whom were previously healthy. Subtyping of the H influenzae type b isolates according to the major outer membrane protein subtype, biotype, and lipopolysaccharide serotype showed that patterns that were uncommon (14%) among children were more common (27%) in the adults.


Pkd2l1 is required for mechanoception in cerebrospinal fluid-contacting neurons and maintenance of spine curvature.
Defects in cerebrospinal fluid (CSF) flow may contribute to idiopathic scoliosis. However, the mechanisms underlying detection of CSF flow in the central canal of the spinal cord are unknown. Here we demonstrate that CSF flows bidirectionally along the antero-posterior axis in the central canal of zebrafish embryos. In the cfap298tm304 mutant, reduction of cilia motility slows transport posteriorly down the central canal and abolishes spontaneous activity of CSF-contacting neurons (CSF-cNs). Loss of the sensory Pkd2l1 channel nearly abolishes CSF-cN calcium activity and single channel opening. Recording from isolated CSF-cNs in vitro, we show that CSF-cNs are mechanosensory and require Pkd2l1 to respond to pressure. Additionally, adult pkd2l1 mutant zebrafish develop an exaggerated spine curvature, reminiscent of kyphosis in humans. These results indicate that CSF-cNs are mechanosensory cells whose Pkd2l1-driven spontaneous activity reflects CSF flow in vivo. Furthermore, Pkd2l1 in CSF-cNs contributes to maintenance of natural curvature of the spine.


Decompensation of the retinal pigment epithelium and occult choroidal neovascularization: indications for treatment.
Degenerative changes in the retinal pigment epithelium (RPE) may compromise the patient's visual acuity before the development of frank choroidal (subretinal) neovascularization. A decompensation of the barrier function of the RPE may permit accumulation of subretinal fluid and sub- or intraretinal hard, yellow exudate. Laser treatment may control this inimical process which threatens or impairs vision and may prevent or delay its progression.


Efficacy of High-Dose Chemotherapy and Three-Dimensional Conformal Radiation for Atypical Teratoid/Rhabdoid Tumor: A Report From the Children's Oncology Group Trial ACNS0333.
Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive, early-childhood brain tumor without standard effective treatment. To our knowledge, we conducted the first AT/RT-specific cooperative group trial, ACNS0333, to examine the efficacy and safety of intensive postoperative chemotherapy and focal radiation to treat AT/RT. Patients from birth to 22 years of age with AT/RT were eligible. After surgery, they received 2 courses of multiagent chemotherapy, followed by 3 courses of high-dose chemotherapy with peripheral blood stem cell rescue and involved-field radiation therapy. Timing of radiation was based on patient age and disease location and extent. Central testing of tumor and blood for SMARCB1 status was mandated. Tumor molecular subclassification was performed retrospectively. The primary analysis was event-free survival (EFS) for patients < 36 months of age compared with a cooperative groups' historical cohort. Although accrual was based on the therapeutic question, potential prognostic factors, including age, tumor location, M stage, surgical resection, order of therapy, germline status, and molecular subtype, were explored. Of 65 evaluable patients, 54 were < 36 months of age. ACNS0333 therapy significantly reduced the risk of EFS events in patients < 36 months of age compared with the historical cohort (P < .0005; hazard rate, 0.43; 95% CI, 0.28 to 0.66). Four-year EFS and overall survival for the entire cohort were 37% (95% CI, 25% to 49%) and 43% (95% CI, 31% to 55%), respectively. Timing of radiation did not affect survival, and 91% of relapses occurred by 2 years from enrollment. Treatment-related deaths occurred in 4 patients. The ACNS0333 regimen dramatically improved survival compared with historical therapies for patients with AT/RT. Clinical characteristics and molecular subgrouping suggest prognostic differences. ACNS0333 results lay a foundation on which to build future studies and incorporate testing of new therapeutic agents.


Membrane-assisted growth of DNA origami nanostructure arrays.
Biological membranes fulfill many important tasks within living organisms. In addition to separating cellular volumes, membranes confine the space available to membrane-associated proteins to two dimensions (2D), which greatly increases their probability to interact with each other and assemble into multiprotein complexes. We here employed two DNA origami structures functionalized with cholesterol moieties as membrane anchors--a three-layered rectangular block and a Y-shaped DNA structure--to mimic membrane-assisted assembly into hierarchical superstructures on supported lipid bilayers and small unilamellar vesicles. As designed, the DNA constructs adhered to the lipid bilayers mediated by the cholesterol anchors and diffused freely in 2D with diffusion coefficients depending on their size and number of cholesterol modifications. Different sets of multimerization oligonucleotides added to bilayer-bound origami block structures induced the growth of either linear polymers or two-dimensional lattices on the membrane. Y-shaped DNA origami structures associated into triskelion homotrimers and further assembled into weakly ordered arrays of hexagons and pentagons, which resembled the geometry of clathrin-coated pits. Our results demonstrate the potential to realize artificial self-assembling systems that mimic the hierarchical formation of polyhedral lattices on cytoplasmic membranes.


Needle gauge and tip designs for preventing post-dural puncture headache (PDPH).
Post-dural puncture headache (PDPH) is one of the most common complications of diagnostic and therapeutic lumbar punctures. PDPH is defined as any headache occurring after a lumbar puncture that worsens within 15 minutes of sitting or standing and is relieved within 15 minutes of the patient lying down. Researchers have suggested many types of interventions to help prevent PDPH. It has been suggested that aspects such as needle tip and gauge can be modified to decrease the incidence of PDPH. To assess the effects of needle tip design (traumatic versus atraumatic) and diameter (gauge) on the prevention of PDPH in participants who have undergone dural puncture for diagnostic or therapeutic causes. We searched CENTRAL, MEDLINE, Embase, CINAHL and LILACS, as well as trial registries via the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal in September 2016. We adopted the MEDLINE strategy for searching the other databases. The search terms we used were a combination of thesaurus-based and free-text terms for both interventions (lumbar puncture in neurological, anaesthesia or myelography settings) and headache. We included randomized controlled trials (RCTs) conducted in any clinical/research setting where dural puncture had been used in participants of all ages and both genders, which compared different tip designs or diameters for prevention of PDPH DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We included 70 studies in the review; 66 studies with 17,067 participants were included in the quantitative analysis. An additional 18 studies are awaiting classification and 12 are ongoing. Fifteen of the 18 studies awaiting classification mainly correspond to congress summaries published before 2010, in which the available information does not allow the complete evaluation of all their risks of bias and characteristics. Our main outcome was prevention of PDPH, but we also assessed the onset of severe PDPH, headache in general and adverse events. The quality of evidence was moderate for most of the outcomes mainly due to risk of bias issues. For the analysis, we undertook three main comparisons: 1) traumatic needles versus atraumatic needles; 2) larger gauge traumatic needles versus smaller gauge traumatic needles; and 3) larger gauge atraumatic needles versus smaller gauge atraumatic needles. For each main comparison, if data were available, we performed a subgroup analysis evaluating lumbar puncture indication, age and posture.For the first comparison, the use of traumatic needles showed a higher risk of onset of PDPH compared to atraumatic needles (36 studies, 9378 participants, risk ratio (RR) 2.14, 95% confidence interval (CI) 1.72 to 2.67, I2 = 9%).In the second comparison of traumatic needles, studies comparing various sizes of large and small gauges showed no significant difference in effects in terms of risk of PDPH, with the exception of one study comparing 26 and 27 gauge needles (one study, 658 participants, RR 6.47, 95% CI 2.55 to 16.43).In the third comparison of atraumatic needles, studies comparing various sizes of large and small gauges showed no significant difference in effects in terms of risk of PDPH.We observed no significant difference in the risk of paraesthesia, backache, severe PDPH and any headache between traumatic and atraumatic needles. Sensitivity analyses of PDPH results between traumatic and atraumatic needles omitting high risk of bias studies showed similar results regarding the benefit of atraumatic needles in the prevention of PDPH (three studies, RR 2.78, 95% CI 1.26 to 6.15; I2 = 51%). There is moderate-quality evidence that atraumatic needles reduce the risk of post-dural puncture headache (PDPH) without increasing adverse events such as paraesthesia or backache. The studies did not report very clearly on aspects related to randomization, such as random sequence generation and allocation concealment, making it difficult to interpret the risk of bias in the included studies. The moderate quality of the evidence for traumatic versus atraumatic needles suggests that further research is likely to have an important impact on our confidence in the estimate of effect.


Discovery of STAT3 Inhibitors: Recent Advances and Future Perspectives.
STAT3 (signal transducer and activator of transcription 3) is a member of the STAT family of proteins that function as signal transducers and transcription factors. Previous research has demonstrated its importance in cell proliferation, differentiation, apoptosis, and immunological and inflammatory responses. Targeting the STAT3 protein has recently been hailed as a viable cancer therapeutic method. Even though none of these inhibitors have yet been exploited in clinical cancer therapy, a small number have made them into clinical trials, leading researchers to explore more promising inhibitors. Based on the mechanism of STAT3 activation, several types of STAT3 inhibitors were described and summarized according to their origins, structures, bioactivity and mechanism of action. Direct inhibition of STAT3 mainly targeted one of the three distinct structural regions of the protein, namely the SH2 domain, the DNA binding domain, and the coiled-coil domain. The progress in STAT3 inhibitor discovery from 2010 to 2021 is comprehensively summarized in this review. STAT3 inhibitors are mainly classified into small molecule inhibitors, natural product inhibitors, and peptides/peptidomimetics. Moreover, it also covers relevant analogues, as well as their core framework. Small-molecule inhibitors of STAT3 like BP-1-102 and BTP analogues displayed great potential against various cancers, while natural products, as well as peptide and peptidomimetics, also showed promising application. Therefore, STAT3 has become a promising target with great research value, and the development of STAT3 inhibitors may provide more therapeutic strategies for STAT3-related diseases.


Loss of suppressor loci on chromosomes 11 and 14 may be required for radiation-induced neoplastic transformation of HeLa x skin fibroblast human cell hybrids.
We have previously reported a linkage between radiation-induced damage to a putative tumor suppressor locus on fibroblast chromosome 11 and the re-expression of tumorigenicity in a hybrid cell line (HeLa x human skin fibroblast) used to study neoplastic transformation. Further investigation into the molecular basis of radiation-induced neoplastic transformation of the hybrid cell, CGL1, indicates that loss of fibroblast chromosome 11 appears to be necessary but not sufficient for neoplastic transformation. Previous analysis had suggested, though not clearly demonstrated, a possible role for loss of alleles on fibroblast chromosome 14 in the neoplastic transformation of the hybrid cells. Therefore, the status of chromosome 14 in the gamma-ray-induced, neoplastically transformed (GIM) hybrid cell lines and in nontumorigenic control (CON) hybrid cell lines isolated from irradiated populations has been investigated. Chromosome painting and molecular studies using restriction fragment length polymorphisms and tetranucleotide repeat polymorphism analysis were performed. As an additional control, the status of chromosome 12 was also examined. We report that five of the eight GIM cell lines have lost one complete copy of a fibroblast chromosome 14 while only one of the five CON cell lines has lost a complete copy of a fibroblast chromosome 14. No evidence of large-scale loss of chromosome 12 was detected in the GIM or CON cells. The data further suggest that both copies of fibroblast chromosome 14 contain an active tumor suppressor locus and that radiation-induced loss of either fibroblast chromosome 14 is associated with neoplastic transformation in this system. We now conclude that loss of alleles on both fibroblast chromosome 11 and 14 may be required for the radiation-induced neoplastic transformation of these human hybrid cells.


Post-transcriptional regulation of FUS and EWS protein expression by miR-141 during neural differentiation.
Brain development involves proliferation, migration and specification of neural progenitor cells, culminating in neuronal circuit formation. Mounting evidence indicates that improper regulation of RNA binding proteins (RBPs), including members of the FET (FUS, EWS, TAF15) family, results in defective cortical development and/or neurodegenerative disorders. However, in spite of their physiological relevance, the precise pattern of FET protein expression in developing neurons is largely unknown. Herein, we found that FUS, EWS and TAF15 expression is differentially regulated during brain development, both in time and in space. In particular, our study identifies a fine-tuned regulation of FUS and EWS during neuronal differentiation, whereas TAF15 appears to be more constitutively expressed. Mechanistically FUS and EWS protein expression is regulated at the post-transcriptional level during neuron differentiation and brain development. Moreover, we identified miR-141 as a key regulator of these FET proteins that modulate their expression levels in differentiating neuronal cells. Thus, our studies uncover a novel link between post-transcriptional regulation of FET proteins expression and neurogenesis.


Breaking the Nd3+-sensitized upconversion nanoparticles myth about the need of onion-layered structures.
Up to now, most strategies to build efficient 800 nm-light responsive upconversion nanoparticles (UCNPs) have included onion-layered structures, in which Nd3+ is confined within the inorganic crystal structure of at least one layer. We report here an easy room-temperature modular preparation of core-shell UCNPs consisting of NaYF4:Yb,Er(Tm)/NaYF4 (UCCS) with Nd3+ anchored at the organic capping by using cucurbituril[7] (CB[7]) as an adhesive. Strikingly, excitation at 800 nm effectively triggers the upconversion emission of UCCS@CB[7]@Nd nanohybrids.


Red and Processed Meat, Poultry, Fish, and Egg Intakes and Cause-Specific and All-Cause Mortality among Men with Nonmetastatic Prostate Cancer in a U.S. Cohort.
Research on the relationship of meat, fish, and egg consumption and mortality among prostate cancer survivors is limited. In the Cancer Prevention Study-II Nutrition Cohort, men diagnosed with nonmetastatic prostate cancer between baseline in 1992/1993 and 2015 were followed for mortality until 2016. Analyses of pre- and postdiagnosis intakes of red and processed meat, poultry, fish, and eggs included 9,286 and 4,882 survivors, respectively. Multivariable-adjusted RRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. A total of 4,682 and 2,768 deaths occurred during follow-up in pre- and postdiagnosis analyses, respectively. Both pre- and postdiagnosis intakes of total red and processed meat were positively associated with all-cause mortality (quartile 4 vs. 1: RR = 1.13; 95% CI, 1.03-1.25; P trend = 0.02; RR = 1.22; 95% CI, 1.07-1.39; P trend = 0.03, respectively), and both pre- and postdiagnosis poultry intakes were inversely associated with all-cause mortality (quartile 4 vs. 1 RR = 0.90; 95% CI, 0.82-0.98; P trend = 0.04; RR = 0.84; 95% CI, 0.75-0.95; P trend = 0.01, respectively). No associations were seen for prostate cancer-specific mortality, except that higher postdiagnosis unprocessed red meat intake was associated with lower risk. Higher red and processed meat, and lower poultry, intakes either before or after prostate cancer diagnosis were associated with higher risk of all-cause mortality. Our findings provide additional evidence that prostate cancer survivors should follow the nutrition guidelines limiting red and processed meat consumption to improve overall survival. Additional research on the relationship of specific meat types and mortality is needed.


Mapping of Enzyme Kinetics on a Microfluidic Device.
A microfluidic platform or "microfluidic mapper" is demonstrated, which in a single experiment performs 36 parallel biochemical reactions with 36 different combinations of two reagents in stepwise concentration gradients. The volume used in each individual reaction was 36 nl. With the microfluidic mapper, we obtained a 3D enzyme reaction plot of horseradish peroxidase (HRP) with Amplex Red (AR) and hydrogen peroxide (H2O2), for concentration ranges of 11.7 μM to 100.0 μM and 11.1 μM to 66.7 μM for AR and H2O2, respectively. This system and methodology could be used as a fast analytical tool to evaluate various chemical and biochemical reactions especially where two or more reagents interact with each other. The generation of dual concentration gradients in the present format has many advantages such as parallelization of reactions in a nanoliter-scale volume and the real-time monitoring of processes leading to quick concentration gradients. The microfluidic mapper could be applied to various problems in analytical chemistry such as revealing of binding kinetics, and optimization of reaction kinetics.


Comparison of the POSSUM score and P-POSSUM score in patients with femoral neck fracture.
The ageing of the population in developed countries has led to an increased number of patients with hip fractures all over the world. POSSUM and P-POSSUM scores predict morbidity and mortality of patients who will be undergoing a surgical treatment. The aim of this study was to evaluate accuracy of these two scores in hip-fractured patients. Between January and December 2012, in our department 144 patients were hospitalised for femoral neck fractures according to the grade III or IV of Garden's classification treated with total hip arthroplasty or endoprosthesis. POSSUM scores and P-POSSUM scores were calculated for each patient with complete clinical data. We then calculated the observed and the expected ratio. 134 patients were eligible: 110 females and 24 males. The mean age for women was 79 years, and the mean age for men was 84 years. We observed 13 deaths and 66 complications. The POSSUM scores predicted 16 deaths and 60 complications, while P-POSSUM scores predicted 6 deaths. The O/E ratio for POSSUM mortality was 0.81 and for P-POSSUM was 2.17, while POSSUM morbidity was 1.1. In our study, we have shown that on the one hand, the POSSUM score predicted accurately both the mortality and morbidity in patients undergoing surgery for the femoral neck fracture, while on the other hand, the P-POSSUM score underestimated them. For this reason, we believe that the POSSUM is indeed a good audit tool, which can accurately predict both mortality and morbidity in a cohort of patients.


Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.
Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667. Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001). A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.


[Calculation of isochromatics and isoclinics of the cornea].
A method of calculating tensions in the eye cornea was described. These tensions were provoked by mechanical influence of oculomotor muscles and intra-ocular pressure. The influence of gradient thickness of the cornea on the form of isochromatics was shown. The nature of cross of the cornea, which represents lines of principal tensions was established. The method is suitable for calculating tensions not only for healthy eyes, but for the eyes with pathological oculomotor apparatus.


Dynamical analysis of the calcium signaling pathway in cardiac myocytes based on logarithmic sensitivity analysis.
Many cellular functions are regulated by the Ca(2+) signal which contains specific information in the form of frequency, amplitude, and duration of the oscillatory dynamics. Any alterations or dysfunctions of components in the calcium signaling pathway of cardiac myocytes may lead to a diverse range of cardiac diseases including hypertrophy and heart failure. In this study, we have investigated the hidden dynamics of the intracellular Ca(2+) signaling and the functional roles of its regulatory mechanism through in silico simulations and parameter sensitivity analysis based on an experimentally verified mathematical model. It was revealed that the Ca(2+) dynamics of cardiac myocytes are determined by the balance among various system parameters. Moreover, it was found through the parameter sensitivity analysis that the self-oscillatory Ca(2+) dynamics are most sensitive to the Ca(2+) leakage rate of the sarcolemmal membrane and the maximum rate of NCX, suggesting that these two components have dominant effects on circulating the cytosolic Ca(2+).


Hybrid Docking-QSAR Studies of 1, 4-dihydropyridine-3, 5-Dicarboxamides as Potential Antitubercular Agents.
Tuberculosis is one of the main medical problems and some people are suffering still from this infectious disease. 1, 4-dihydropyridines are multi-target ligands that recently are recognized as anti-tubercular agents. In the current research, computational studies were conducted of some synthesized 1, 4- dihydropyridine-3, 5-dicarboxamides in non-hydrolyzed and hydrolyzed forms to find the drugreceptor interactions profile. Among equations obtained for non-hydrolyzed compounds, the model with better statistical parameters such as R2= 0.9462, q2 of LOO= 0.8318 and q2 of LMO= 0.7987 was considered as the best one and EEig08d, LAI, Mor23m, GATS3e, Mor28m descriptors were identified as the most significant factors that affect the biological activity of non-hydrolyzed compounds. In the hydrolyzed compounds, the model which has R2= 0.9731, q2 of LOO= 0.91154462 and q2 of LMO= 0.742 was considered as the best one and Mor27e and BEHv2 were also revealed as the most important descriptors in hydrolyzed compounds.


The development and validation of a neuropathy- and foot ulcer-specific quality of life instrument.
The purpose of this study was to develop a questionnaire that measures patients' perceptions of the impact of diabetic peripheral neuropathy and foot ulcers on their quality of life and to assess the psychometric properties of this instrument in a sample of patients with varying severity and symptomatology of diabetic peripheral neuropathy. The neuropathy- and foot ulcer-specific quality of life instrument (NeuroQoL), generated from interviews with patients with (n = 47) and without (n = 15) diabetic peripheral neuropathy, was administered to 418 consecutive patients with diabetic peripheral neuropathy (35% with foot ulcer history) attending either U.K. (n = 290) or U.S. (n = 128) diabetes centers. Psychometric tests of NeuroQoL included factor analyses and internal consistency of scales; a series of multivariate analyses were performed to establish its criterion, construct, and incremental validity. Results were compared with those obtained using the Short Form (SF)-12 measure of health-related functioning. Factor analyses of NeuroQoL revealed three physical symptom measures and two psychosocial functioning measures with good reliability (alpha = 0.86-0.95). NeuroQoL was more strongly associated with measures of neuropathic severity than SF-12, more fully mediated the relationship of diabetic peripheral neuropathy with overall quality of life, and significantly increased explained variance in overall quality of life over SF-12. NeuroQoL reliably captures the key dimensions of the patients' experience of diabetic peripheral neuropathy and is a valid tool for studying the impact of neuropathy and foot ulceration on quality of life.


Despite structural similarities between gp91phox and FRE1, flavocytochrome b558 does not mediate iron uptake by myeloid cells.
Superoxide (O2-) generated by the phagocyte reduced nicotinamide adenine dinucleotide phosphate oxidase is dependent on electron transfer by flavocytochrome b558 (flavocytochrome b), a transmembrane heterodimer that forms the redox center of the oxidase at the plasma or phagosomal membrane. The larger of its two subunits, gp91phox, is homologous to the yeast iron reductase subunit FRE1, and these two proteins share many structural and functional characteristics. Because FRE1 is required for iron uptake in yeast, we hypothesized that flavocytochrome b might serve a similar function in human phagocytes and thus provide a mechanism for the transferrin-independent iron acquisition observed in myeloid cells. To determine whether flavocytochrome b was required for iron uptake, we compared iron acquisition by polymorphonuclear neutrophils (PMNs) or Epstein-Barr virus (EBV)-transformed B lymphocytes derived from individuals with X-linked chronic granulomatous disease (CGD) with iron acquisition by normal cells. Our results indicate that all cells acquired iron to the same extent and that uptake could be significantly enhanced in the presence of the trivalent metal gallium. The gallium enhancement of iron uptake observed in PMNs or in EBV-transformed B lymphocytes derived from healthy individuals was mirrored by those derived from individuals deficient in flavocytochrome b. Furthermore, both normal and CGD-derived EBV-transformed B lymphocytes had similar iron reductase activity, suggesting that flavocytochrome b is not a biologically significant iron reductase. In contrast to previously suggested hypotheses, these results show conclusively that flavocytochrome b is not necessary for cellular iron acquisition, despite structural and functional similarities between yeast iron reductases and flavocytochrome b.


Childhood bullying involvement and exposure to intimate partner violence.
Our objectives with this study were to describe the prevalence of bullying involvement (ie, bullying and victimization) among children from a multigenerational study and to examine the relationship of these childhood behaviors and exposure to intimate partner violence. A community-based cohort of 112 children (aged 6 to 13 years) was asked to self-report on physical, verbal, and relational types of bullying and victimization experienced in the past year. Parents reported on their child's externalizing and internalizing behaviors during the previous 6 months using items from Achenbach's Child Behavior Checklist. The frequency of parental experiences of intimate partner violence perpetration and victimization at 2 time points during the preceding 5 years was measured using Conflict Tactics Scale items. The association of intimate partner violence and parent-reported child behavioral problems was examined, followed by exposure to intimate partner violence and child-reported bullying or victimization. Parental risk factors (eg, race/ethnicity, education, problem drinking) that predispose to intimate partner violence were controlled for using propensity score statistical modeling. Eighty-two (73.2%) children reported being victimized by peers, and 38 (33.9%) children reported bullying behaviors in the past year. More reports came from girls than from boys (55% for victimization and 61% for bullying). Almost all (97%) child bullies were also victims themselves. Intimate partner violence was reported by parent respondents in 53 (50.5%) households at any or both of the 2 time points. Exposure to intimate partner violence was not associated with child-reported relational bullying behaviors or victimization by peers, However, intimate partner violence-exposed children were at increased risk for problematic levels of externalizing behavior/physical aggression and internalizing behaviors. In our sample, children who were 6 to 13 years of age reported a substantial amount of bullying and victimization; a large majority were bully-victims and female. Regression analyses did not show that children who were exposed to intimate partner violence were more likely to engage in relational bullying. However, children who are exposed to intimate partner violence have a higher likelihood of internalizing behaviors and physical aggression.


Fibril structures of TFG protein mutants validate the identification of TFG as a disease-related amyloid protein by the IMPAcT method.
We previously presented a bioinformatic method for identifying diseases that arise from a mutation in a protein's low-complexity domain that drives the protein into pathogenic amyloid fibrils. One protein so identified was the tropomyosin-receptor kinase-fused gene protein (TRK-fused gene protein or TFG). Mutations in TFG are associated with degenerative neurological conditions. Here, we present experimental evidence that confirms our prediction that these conditions are amyloid-related. We find that the low-complexity domain of TFG containing the disease-related mutations G269V or P285L forms amyloid fibrils, and we determine their structures using cryo-electron microscopy (cryo-EM). These structures are unmistakably amyloid in nature and confirm the propensity of the mutant TFG low-complexity domain to form amyloid fibrils. Also, despite resulting from a pathogenic mutation, the fibril structures bear some similarities to other amyloid structures that are thought to be nonpathogenic and even functional, but there are other factors that support these structures' relevance to disease, including an increased propensity to form amyloid compared with the wild-type sequence, structure-stabilizing influence from the mutant residues themselves, and double-protofilament amyloid cores. Our findings elucidate two potentially disease-relevant structures of a previously unknown amyloid and also show how the structural features of pathogenic amyloid fibrils may not conform to the features commonly associated with pathogenicity.


Legacy, legitimacy, and possibility: an exploration of community health worker experience across the generations in Khayelitsha, South Africa.
In South Africa, the response to HIV and TB epidemics is complex, varied, and contextually defined. "Task-shifting" and a movement toward a decentralized model of care have led to an increased reliance on community health workers (CHWs) providing health care services to residents of impoverished, peri-urban areas. Public health policy tends to present CHWs as a homogeneous group, with little attention paid to the nuances of experience, motivation, and understanding, which distinguish these care workers from one another and from other kinds of health workers. An exploration of the layered meanings of providing community health care services under financially, politically, and socially difficult conditions reveals clear distinctions of experience across the generations. Many older CHWs say that ubuntu, a notion of shared African humanity, is being "killed off" by the younger generation, whereas younger CHWs often describe older women as being "jealous" of the opportunities that this younger generation has for education, training, and employment. The structure of the South African health system, past and present responses to disease epidemics, and the legacy of apartheid's structural violence have amplified these generational differences among CHWs. Using ethnographic data collected from approximately 20 CHWS in a peri-urban settlement in Cape Town, South Africa, I explore how CHWs experience and understand legitimacy in the moral economy of care. A call for closer attention to the experiences of CHWs is critical when designing public health policies for the delivery of health care services in impoverished communities in South Africa.


A mathematical evaluation of hemodynamic parameters after carotid eversion and conventional patch angioplasty.
Carotid endarterectomy has a long history in stroke prevention, yet controversy remains concerning optimal techniques. Two methods frequently used are endarterectomy with patch angioplasty (CEAP) and eversion endarterectomy (CEE). The objective of this study was to compare hemodynamics-related stress and strain distributions between arteries repaired using CEAP and CEE. Mathematical models were based on in vivo three-dimensional arterial geometry, pulsatile velocity profiles, and intraluminal pressure inputs obtained from 16 patients with carotid artery disease. These data were combined with experimentally derived nonlinear, anisotropic carotid artery mechanical properties to create fluid-structure interaction models of CEAP and CEE. These models were then used to calculate hemodynamic parameters thought to promote recurrent disease and restenosis. Combining calculations of stress and strain into a composite risk index, called the integral abnormality factor, allowed for an overall comparison between CEAP and CEE. CEE demonstrated lower mechanical stresses in the arterial wall, whereas CEAP straightened the artery and caused high stress and strain concentrations at the suture-artery interface. CEAP produced a larger continuous region of oscillatory, low-shear, vortical flow in the carotid bulb. There was a more than two-fold difference in the integral abnormality factor, favoring CEE. In conclusion, in a realistically simulated carotid artery, fluid-structure interaction modeling demonstrated CEE to produce less mechanical wall stress and improved flow patterns compared with CEAP. Clinical validation with larger numbers of individual patients will ultimately be required to support modeling approaches to help predict arterial disease progression and comparative effectiveness of reconstruction methods and devices.


The Drosophila protein palmitoylome: characterizing palmitoyl-thioesterases and DHHC palmitoyl-transferases.
Palmitoylation is the post-translational addition of a palmitate moiety to a cysteine residue through a covalent thioester bond. The addition and removal of this modification is controlled by both palmitoyl acyl-transferases and thioesterases. Using bioinformatic analysis, we identified 22 DHHC family palmitoyl acyl-transferase homologs in the Drosophila genome. We used in situ hybridization,RT-PCR, and published FlyAtlas microarray data to characterize the expression patterns of all 22 fly homologs. Our results indicate that all are expressed genes, but several, including CG1407, CG4676, CG5620, CG6017/dHIP14, CG6618, CG6627 and CG17257 appear to be enriched in neural tissues suggesting that they are important for neural function. Furthermore, we have found that several may be expressed in a sex-specific manner with adult male specific expression of CG4483 and CG17195. Using tagged versions of the DHHC genes, we demonstrate that fly DHHC proteins are primarily located in either the Golgi Apparatus or Endoplasmic Reticulum in S2 cells, except for CG1407, which was found on the plasma membrane. We also characterized the subcellular localization and expression of the three known thioesterases: Palmitoyl-protein Thioesterase 1 (Ppt1), Palmitoyl-protein Thioesterase 2 (Ppt2)and Acyl-protein Thioesterase 1 (APT1). Our results indicate that Ppt1 and Ppt2 are the major lysosomal thioesterases while APT1 is the likely cytoplasmic thioesterase. Finally, in vivo rescue experiments show that Ppt2 expression cannot rescue the neural inclusion phenotypes associated with loss of Ppt1, further supporting distinct functions and substrates for these two thioesterases. These results will serve as the basis for a more complete understanding of the protein palmitoylome's normal cellular functions in the fly and will lead to further insights into the molecular etiology of diseases associated with the mis-regulation of palmitoylation.


Iridoid glycosides from Barleria trispinosa.
A new iridoid glycoside and three known iridoid glycosides were isolated from the aerial parts of Barleria trispinosa. The structure of the new compound was determined as 6-alpha-L-rhamnopyranosyl-8-O-acetylshanzihiside methyl ester. The known compounds were identified as 6,8-O,O-diacetylshanhiside methyl ester (acetyl barlerin), 8-O-acetylshanzhiside methyl ester (barlerin) and shanzhiside methyl ester, which were isolated from the plant for the first time. The structures of the isolated compounds were elucidated by spectroscopic evidence, mainly one- and two-dimensional proton and carbon-13 NMR spectroscopy.


Development of a resonant-type microwave reactor and its application to the synthesis of positron emission tomography radiopharmaceuticals.
Microwave technology has been successfully applied to enhance the effectiveness of radiolabeling reactions. The use of a microwave as a source of heat energy can allow chemical reactions to proceed over much shorter reaction times and in higher yields than they would do under conventional thermal conditions. A microwave reactor developed by Resonance Instrument Inc. (Model 520/521) and CEM (PETWave) has been used exclusively for the synthesis of radiolabeled agents for positron emission tomography by numerous groups throughout the world. In this study, we have developed a novel resonant-type microwave reactor powered by a solid-state device and confirmed that this system can focus microwave power on a small amount of reaction solution. Furthermore, we have demonstrated the rapid and facile radiosynthesis of 16α-[(18)F]fluoroestradiol, 4-[(18)F]fluoro-N-[2-(1-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinylbenzamide, and N-succinimidyl 4-[(18)F]fluorobenzoate using our newly developed microwave reactor.


Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters.
In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped. In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.


Insights on the emerging biotechnology of histidine-rich peptides.
In the late 70's, the discovery of the restriction enzymes made possible the biological production of functional proteins by recombinant DNA technologies, a fact that largely empowered both biotechnological and pharmaceutical industries. Short peptides or small protein domains, with specific molecular affinities, were developed as purification tags in downstream processes to separate the target protein from the culture media or cell debris, upon breaking the producing cells. Among these tags, and by exploiting the interactivity of the imidazole ring of histidine residues, the hexahistidine peptide (H6) became a gold standard. Although initially used almost exclusively in protein production, H6 and related His-rich peptides are progressively proving a broad applicability in novel utilities including enzymatic processes, advanced drug delivery systems and diagnosis, through a so far unsuspected adaptation of their binding capabilities. In this context, the coordination of histidine residues and metals confers intriguing functionalities to His-rich sequences useable in the forward-thinking design of protein-based nano- and micro-materials and devices, through strategies that are comprehensively presented here.


Drugs of Abuse Differentially Alter the Neuronal Excitability of Prefrontal Layer V Pyramidal Cell Subtypes.
The medial prefrontal cortex (mPFC) plays an important role in regulating executive functions including reward seeking, task flexibility, and compulsivity. Studies in humans have demonstrated that drugs of abuse, including heroin, cocaine, methamphetamine, and alcohol, alter prefrontal function resulting in the consequential loss of inhibitory control and increased compulsive behaviors, including drug seeking. Within the mPFC, layer V pyramidal cells, which are delineated into two major subtypes (type I and type II, which project to subcortical or commissurally to other cortical regions, respectively), serve as the major output cells which integrate information from other cortical and subcortical regions and mediate executive control. Preclinical studies examining changes in cellular physiology in the mPFC in response to drugs of abuse, especially in regard to layer V pyramidal subtypes, are relatively sparse. In the present study, we aimed to explore how heroin, cocaine, methamphetamine, ethanol, and 3,4-methylenedioxypyrovalerone (MDPV) alter the baseline cellular physiology and excitability properties of layer V pyramidal cell subtypes. Specifically, animals were exposed to experimenter delivered [intraperitoneal (i.p.)] heroin, cocaine, the cocaine-like synthetic cathinone MDPV, methamphetamine, ethanol, or saline as a control once daily for five consecutive days. On the fifth day, whole-cell physiology recordings were conducted from type I and type II layer V pyramidal cells in the mPFC. Changes in cellular excitability, including rheobase (i.e., the amount of injected current required to elicit action potentials), changes in input/output curves, as well as spiking characteristics induced by each substance, were assessed. We found that heroin, cocaine, methamphetamine, and MDPV decreased the excitability of type II cells, whereas ethanol increased the excitability of type I pyramidal cells. Together, these results suggest that heroin, cocaine, MDPV, and methamphetamine reduce mPFC commissural output by reducing type II excitability, while ethanol increases the excitability of type I cells targeting subcortical structures. Thus, separate classes of abused drugs differentially affect layer V pyramidal subtypes in the mPFC, which may ultimately give rise to compulsivity and inappropriate synaptic plasticity underlying substance use disorders.


A common epitope on platelet integrin alpha IIb beta 3 (glycoprotein IIbIIIa; CD41b/CD61) and alpha M beta 2 (Mac-1; CDIIb/CD18) detected by a monoclonal antibody.
Evidence is presented that the mAb 25E11, directed against the platelet integrin alpha IIb beta 3 (glycoprotein IIbIIIa;CD41b/CD61) also binds the distinct myeloid cell integrin alpha M beta 2 (Mac-1;CDIIb/CD18). The Ab is shown to identify only the alpha IIb beta 3 integrin complex and not the individual subunits in crossed Ab immunoelectrophoresis of platelet lysate. From cultured human macrophages, sequential immunoprecipitation of labeled glycoproteins indicated that 25E11 also bound the Mac-1 (CD11b/CD18) complex. This was confirmed using COS-7 and WOP cells doubly transfected with alpha M (CD11b) and beta 2 (CD18) or with alpha L (CD11a) and beta 2 when it was found that the Ab bound only the alpha M beta 2 transfectants. Studies with these cells and the RC2A myeloid cell line stimulated with tetradecanoyl phorbol acetate or FMLP indicated that the 25E11 epitope on Mac-1 did not depend on cell activation for its expression. The rationale for this cross-reactivity is not known, but since the 25E11 Ab inhibits the function of both platelets and myeloid cells, it is likely that this shared epitope is important to integrin function. Given the expression of this epitope on IIbIIIa and Mac-1, the dominant integrins of platelets and granulocyte/macrophage cells, but not on other integrins, a role of this epitope in the early events of inflammation is suggested.


[Mental health in Eastern Lille: a future of network-psychiatry?]
For some time now, East Lille has been working with a relatively modern mental health care system that remarkably resembles Dutch health care with the same values and norms that we want to implement in the Netherlands as well.
 AIM: Gaining inspiration to further investigate regional cooperation and 'network care' in Dutch psychiatry.
 METHOD: A delegation from the board of f-act-Netherlands and ccaf paid a working visit to Lille.
 RESULTS: The basis of the East Lille working method is a charter of shared values developed with all parties, clients, relatives, employees and external professionals, which is signed by every professional. In case of doubt, a change of context or the introduction of new working methods, these values are used first. CONCLUSIONS High quality mental health care develops in dialogue, in which working methods, service delivery models and interventions are linked to each other by means of network care. Through reflection, moral deliberation and appreciative auditing, care is progressively improved. These procedures guarantee a modern process of quality improvement.


Gastroduodenal mucosa in uraemia: endoscopic and histological correlation and prevalence of helicobacter-like organisms.
This study aimed to determine the prevalence of endoscopic and histological gastroduodenitis as well as helicobacter-like organisms in patients with end stage renal failure undergoing maintenance dialysis treatment. A total of 322 out of 422 patients in our dialysis programme underwent endoscopy and gastroduodenal biopsy specimens were taken from 260. Endoscopic gastroduodenitis occurred in 158 (49%). Histological gastritis occurred in the gastric body or antrum in 134 patients (52%) and duodenitis in 52 (21%). There was no correlation between endoscopic and histological gastritis in contrast to a significant correlation for duodenitis. Helicobacter-like organisms occurred in the body or antrum in 81 (31%). Their presence was associated with gastritis--in particular acute and acute on chronic gastritis rather than chronic gastritis. Patients with gastritis were significantly older than those without (p less than 0.001) and had lower basal and peak acid outputs.


Single-incision robotic assisted surgery: a nonrandomized cohort pilot study on a novel surgical platform in colorectal surgery.
The technological barriers and steep learning curve of single-incision laparoscopic surgery had kept it from further applications. A literature review had reported that robotic technology could preserve its advantages while simplifying its difficulties. This nonrandomized cohort pilot study aims to evaluate the feasibility and safety of single-incision robotic assisted colorectal surgery based on a novel robotic surgical platform, the SHURUI Endoscopic Surgical Robotic System (SR-ENS-600). This study enrolled 7 patients with colorectal malignancy who underwent single-incision robotic assisted surgery (SIRAS) at a tertiary general surgery center, and retrospectively included 23 patients who underwent robotic assisted surgery from September 2015 to June 2016 and 35 patients who underwent single-incision laparoscopic surgery from June 2017 to March 2018, which were labeled as the initial in-learning-curve attempts from the same surgical team. The technological feasibility and safety of SIRAS were evaluated. Perioperative outcomes, short-term postoperative outcomes, clinicopathologic outcomes, and follow-up were reported. Six SIRAS operations were completed successfully without eventful intraoperative complications, except for one operation that encountered a large-volume of intraoperative hemorrhage. Two SIRAS cases were converted to multiport laparoscopic surgery because of intraoperative hemorrhage and difficulty in retraction. Postoperative pathology reported satisfactory specimen qualities. There were no short-term postoperative complications, no short-term mortality, no tumor recurrence, or metastasis reported. There was one incisional hernia reported half a year after operation. Patients with advanced staging were sent to standard evaluation and chemotherapy, and follow-up is still on-going. SIRAS can be feasibly performed by a skilled surgical team via the SR-ENS-600 platform for strictly-selected patients, which provides preferable instrument maneuverability and stability in confined surgical fields and overcomes the technical difficulty of multisite dissection through a single-incision. Large-volume investigations and high-level evidences are required to further validate its safety and superiority.


[Integral indices of the automatically reproduced spatial QRS loop in the diagnosis of different forms of myocardial hypertrophy].
A total of 249 patients with arterial hypertension taking a variety of clinical forms, primary pulmonary hypertension, dilatation cardiomyopathy, congenital heart diseases with secondary pulmonary hypertension were examined and allocated to 3 groups: 125 patients with left-ventricular hypertrophy (LVH) (group 1); 44 patients with right-ventricular hypertrophy (RVH) (group 2), and 80 patients with combined hypertrophy of both ventricles (CH). Eighty-one normal subjects were taken as controls. New parameters of diagnostic significance were identified by automated reproduction of vectorcardiographic spatial QRSxyz loop (the Macfee-Parungao system) and computer analysis of vectorcardiographic parameters, that improve electrocardiographic diagnosis of cardiac hypertrophies, as compared to the conventional criteria, bringing its accuracy to 88.8% for LVH, 100% for RVH, and 45% for CH. Typical features of myocardial hypertrophy at large are increased area enclosed by the spatial loop (SQRS greater than 3.4 mV2) and/or increased mean vector (LQRSxyz greater than 0.76 mV), while Lx greater than 0.6 mV and/or Lz less than -0.4 mV were specific for LVH; Lx less than 0.05 mV was specific for RVH, and the H angle ranging from -70 degrees to -140 degrees or H of -60 degrees to -140 degrees at Lz less than 1.1 mV, or -50 degrees to -140 degrees at Lz less than 1.5 mV were specific for CH.


Ionizing radiation sensitizes erythroleukemic cells but not normal erythroblasts to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)--mediated cytotoxicity by selective up-regulation of TRAIL-R1.
Cytotoxic activity of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand), used alone or in different combinations with either a low (1.5 Gy) or a high (15 Gy) single dose of ionizing radiation (IR), was investigated on erythroleukemic cells (K562, HEL, Friend, primary leukemic erythroblasts) and on primary CD34(+)-derived normal erythroblasts. Human recombinant TRAIL alone variably affected the survival/growth of erythroleukemic cells; K562 cells were the most sensitive. Moreover, all erythroleukemic cells were radio-resistant, as demonstrated by the fact that cytotoxicity was evident only after treatment with high-dose (15 Gy) IR. Remarkably, when IR and TRAIL were used in combination, an additive effect was noticed in all erythroleukemic cells. Augmentation of TRAIL-induced cell death by IR was observed with both low and high IR doses and required the sequential treatment of IR 3 to 6 hours before the addition of TRAIL. Conversely, both TRAIL and IR showed a moderate cytotoxicity on primary CD34(+)-derived normal erythroblasts when used alone, but their combination did not show any additive effect. Moreover, the cytotoxicity of IR plus TRAIL observed in erythroleukemic cells was accompanied by the selective up-regulation of the surface expression of TRAIL-R1 (DR4), and it was completely blocked by the z-Val-Ala-Asp (OMe)-CH(2) (z-VAD-fmk) caspase inhibitor. On the other hand, the surface expression of TRAIL-R1 in CD34(+)-derived normal erythroblasts was unaffected by IR, which induced the up-regulation of the decoy TRAIL-R3. These data demonstrate that treatment with IR provides an approach to selectively sensitize erythroleukemic cells, but not normal erythroblasts, to TRAIL-induced apoptosis through the functional up-regulation of TRAIL-R1.


[Bioavailability and metabolism of flavonoids].
Published data about bioavailability and metabolism of flavonoids are reviewed. Information concerning the absorption of flavonoids in a digestive path and the participation of microorganisms in their hydrolysis is summarized. Parameters of pharmacokinetics are presented for the main classes of flavonoids, including flavanes (flavan-3-ols), anthocyans, flavones, flavonols, and flavanones.


Gel-permeation high-performance liquid chromatography as a powerful technique for rapid analysis of calcitriol (1,25-dihydroxycholecalciferol) receptors.
We used gel-permeation high-performance liquid chromatography to detect cytosolic and nuclear calcitriol (1,25-dihydroxycholecalciferol) receptors. This new convenient technique allowed accurate separation of the calcitriol receptor from other vitamin D-binding proteins. Compared with sucrose-density-gradient centrifugation, it has several advantages including, in particular, its rapidity.


TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas.
The epigenetic mechanisms involved in transcriptional regulation leading to malignant phenotype in gliomas remains poorly understood. Topoisomerase IIB (TOP2B), an enzyme that decoils and releases torsional forces in DNA, is overexpressed in a subset of gliomas. Therefore, we investigated its role in epigenetic regulation in these tumors. To investigate the role of TOP2B in epigenetic regulation in gliomas, we performed paired chromatin immunoprecipitation sequencing for TOP2B and RNA-sequencing analysis of glioma cell lines with and without TOP2B inhibition and in human glioma specimens. These experiments were complemented with assay for transposase-accessible chromatin using sequencing, gene silencing, and mouse xenograft experiments to investigate the function of TOP2B and its role in glioma phenotypes. We discovered that TOP2B modulates transcription of multiple oncogenes in human gliomas. TOP2B regulated transcription only at sites where it was enzymatically active, but not at all native binding sites. In particular, TOP2B activity localized in enhancers, promoters, and introns of PDGFRA and MYC, facilitating their expression. TOP2B levels and genomic localization was associated with PDGFRA and MYC expression across glioma specimens, which was not seen in nontumoral human brain tissue. In vivo, TOP2B knockdown of human glioma intracranial implants prolonged survival and downregulated PDGFRA. Our results indicate that TOP2B activity exerts a pleiotropic role in transcriptional regulation of oncogenes in a subset of gliomas promoting a proliferative phenotype.


Mood and neuropsychological function in depression: the role of corticosteroids and serotonin.
Depressed patients show deficits on neuropsychological tests. However, the basis of these impairments and their relationship with mood disturbance remains unclear. This paper reviews the literature regarding the relationship between mood disturbance and neuropsychological impairment in depression and the evidence for serotonergic and hypothalamic-pituitary-adrenal (HPA) axis involvement in these two domains. Mood disturbance and neuropsychological impairment both occur in depression, but have no clear relationship in time or degree. Impairment of post-synaptic 5-HT1A receptor function may result in the symptom of low mood in depression. Depressed patients demonstrate abnormalities in the functional control of the HPA axis with a resultant hypercortisolaemia, which may impair neuropsychological function. These processes may be related given the extensive interactions between the serotonergic system and the HPA axis. We argue that there is a neurobiological cause of impaired neuropsychological function in depression. The complex relationship between neuropsychological function and mood may be a result of interactions between the serotonergic system and the HPA axis, particularly in the hippocampus with involvement of serotonergic 5-HT1A and glucocorticoid receptors. A primary dysfunction in these receptors will produce a lowering of mood and neuropsychological impairment respectively. Either dysfunction will result in a secondary impairment of the alternate system. Thus, the effective and psychological changes of depressive illness are likely to have complex relationships in time and severity to one another and the illness as a whole may result from a range of primary aetio-pathologies.


Cellular and molecular basis of symbiotic nodule development.
Root nodule development plays a vital role in establishing the mutualistic relationship between legumes and nitrogen-fixing rhizobia. Two primary processes are involved in nodule development: formative cell divisions in the root cortex and the subsequent differentiation of nodule cells. The first process involves the mitotic reactivation of differentiated root cortex cells to form nodule primordium after perceiving symbiotic signals. The second process enables the nascent nodule primordium cells to develop into various cell types, leading to the creation of a functional nodule capable of supporting nitrogen fixation. Thus, both division and differentiation of nodule cells are crucial for root nodule development. This review provides an overview of the most recent advancements in comprehending the cellular and molecular mechanisms underlying symbiotic nodule development in legumes.


A Lipidomics Atlas of Selected Sphingolipids in Multiple Mouse Nervous System Regions.
Many lipids, including sphingolipids, are essential components of the nervous system. Sphingolipids play critical roles in maintaining the membrane structure and integrity and in cell signaling. We used a multi-dimensional mass spectrometry-based shotgun lipidomics platform to selectively analyze the lipid species profiles of ceramide, sphingomyelin, cerebroside, and sulfatide; these four classes of sphingolipids are found in the central nervous system (CNS) (the cerebrum, brain stem, and spinal cord) and peripheral nervous system (PNS) (the sciatic nerve) tissues of young adult wild-type mice. Our results revealed that the lipid species profiles of the four sphingolipid classes in the different nervous tissues were highly distinct. In addition, the mRNA expression of sphingolipid metabolism genes-including the ceramidase synthases that specifically acylate the N-acyl chain of ceramide species and sphingomyelinases that cleave sphingomyelins generating ceramides-were analyzed in the mouse cerebrum and spinal cord tissue in order to better understand the sphingolipid profile differences observed between these nervous tissues. We found that the distinct profiles of the determined sphingolipids were consistent with the high selectivity of ceramide synthases and provided a potential mechanism to explain region-specific CNS ceramide and sphingomyelin levels. In conclusion, we portray for the first time a lipidomics atlas of select sphingolipids in multiple nervous system regions and believe that this type of knowledge could be very useful for better understanding the role of this lipid category in the nervous system.


Treatment and outcomes in diabetic breast cancer patients.
Effective breast cancer management is more complex with diabetes present and may contribute to poor outcomes. Therefore, we conducted two simultaneous systematic reviews to address the association of diabetes with (1) treatment patterns in breast cancer patients and (2) breast cancer recurrence rates or breast cancer-specific and all-cause mortality. We searched major databases for English language peer-reviewed studies through November 2013, which addressed either of the above research questions, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) method. Analyses compared treatment patterns or health outcomes for breast cancer subjects with and without diabetes. We used STROBE quality criteria and conducted a random-effects meta-analysis of all-cause mortality. The review yielded 11 publications for question 1 and 26 for question 2, with nine overlapping. Treatment studies showed chemotherapy was less likely in patients with diabetes. Of 22 studies, 21 assessing all-cause mortality indicated a statistically significant increased overall mortality for patients with diabetes (hazard ratios: 0.33-5.40), with meta-analysis of eligible studies indicating a 52 % increased risk. Nine studies assessing breast cancer-specific mortality had inconsistent results, with five showing significantly increased risk for diabetes patients. Results were inconsistent for recurrence and metastases. The majority of studies reported detrimental associations between diabetes and optimal treatment or all-cause mortality among women with breast cancer. Divergence in variable and outcomes inclusion and definitions, potential participation bias in individual studies, and differing analytic methods make inferences difficult. This review illuminates the importance of the impact of diabetes on breast cancer patients and explicitly recognizes that co-management of conditions is necessary to prevent excess morbidity and mortality.


Survival and Development of Striacosta albicosta (Smith) (Lepidoptera: Noctuidae) Immature Stages on Dry Beans, non-Bt, Cry1F, and Vip3A Maize.
Striacosta albicosta is a crop pest that causes economic damage in the United States and Canada. Only maize and dry beans are shown to be suitable hosts, since larval development is incomplete on other hosts. The objective of this study was to describe the developmental parameters of immature stages of S. albicosta feeding on dry beans, non-Bt, Cry1F, and Vip3A maize. For Vip3A, mortality was 100% after 24 h. Larvae feeding on non-Bt maize had the highest larval survival (70.6%) compared to the other hosts. Maize expressing Cry1F had higher survival (31.3%) than dry beans (26.0%). Larvae feeding on dry beans had a significantly faster total development time (74.8 days), compared to 92.5 days for non-Bt and 96.2 days for Cry1F. All larvae developed through seven instars. Pupae from larvae that had fed on non-Bt maize were significantly heavier than pupae from other hosts. An understanding of S. albicosta immature development on various host plants is needed to improve recommendations for effective scouting, treatment timing, and economic thresholds. Differential development can result in an extended adult emergence period, and possibly result in assortative mating between Bt susceptible and resistant populations, which violates the assumption of random mating necessary for current resistance management strategies for Bt maize. Therefore, understanding the impact of host plant and transgenic traits on aspects of pest biology will aid in developing effective integrated pest management and insect resistance management strategies for this pest.


Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation.
Amyloid beta (Abeta)-containing plaques are surrounded by dystrophic neurites in the Alzheimer's disease (AD) brain, but whether and how plaques induce these neuritic abnormalities remain unknown. We tested the hypothesis that soluble oligomeric assemblies of Abeta, which surround plaques, induce calcium-mediated secondary cascades that lead to dystrophic changes in local neurites. We show that soluble Abeta oligomers lead to activation of the calcium-dependent phosphatase calcineurin (CaN) (PP2B), which in turn activates the transcriptional factor nuclear factor of activated T cells (NFAT). Activation of these signaling pathways, even in the absence of Abeta, is sufficient to produce a virtual phenocopy of Abeta-induced dystrophic neurites, dendritic simplification, and dendritic spine loss in both neurons in culture and in the adult mouse brain. Importantly, the morphological deficits in the vicinity of Abeta deposits in a mouse model of AD are ameliorated by CaN inhibition, supporting the hypothesis that CaN-NFAT are aberrantly activated by Abeta and that CaN-NFAT activation is responsible for disruption of neuronal structure near plaques. In accord with this, we also detect increased levels of an active form of CaN and NFATc4 in the nuclear fraction from the cortex of patients with AD. Thus, Abeta appears to mediate the neurodegeneration of AD, at least in part, by activation of CaN and subsequent NFAT-mediated downstream cascades.


A one-year double-blind placebo-controlled study of the efficacy and safety of almitrine bismesylate in hypoxic COLD patients. Monitoring progress status on 490 patients entered into the VIMS study before January 1st, 1984.
The aim of the VIMS group is to verify the efficacy and acceptability of almitrine bismesylate (ABM) taken orally in the treatment of chronic obstructive bronchitis, by an international long-term study, one year controlled against placebo. This study includes more than 800 out-patients in 70 centres in 12 countries. 490 patients entered the study before 1/1/84, after the first 9 months of the inclusion period. 60% of patients are treated in France, 20% in the U.K. and Ireland and 20% in Belgium, Denmark, Italy, Switzerland. Their mean FEV1 is 0.87 liters, their mean PaO2 is 57 mmHg. The study protocol foresees two control visits separated by a 3 week interval before entry into the study in order to verify the stability of the patients on the basis of clinical, spirometric and gazometric data; the variation in PaO2 is less than or equal to 6 mmHg in more than 90% of the patients. The severity of the disease is assessed by the existence of an hospitalisation during the year preceeding the study in 55% of the patients, the necessity of oxygenotherapy at home for at least 12hr/day in 1/3 of them. The treatment of the latter was attributed separately at random to seek in a prospective manner the interest of associating O2 and ABM. During the study, the mortality of the patients included is 6% and about 70% of the patients completed the study period. The survey of adverse reactions and reasons for treatment interruption is progressively established by close collaboration between the investigators and monitors, to comply with the directives of pharmacosurveillance for severe and polymedicated patients. The analysis of the results to be carried out at the end of the study after verification and correction by the investigators, should enable us to enhance our knowledge of the clinical and gazometric parameters in patients with chronic obstructive disease followed for one year and treated by conventional means (control group) and the activity of ABM in order to confirm its therapeutic value in the treatment of chronic obstructive bronchitis.


Transcriptome Analysis Shows Activation of Stress and Defense Responses by Silencing of Chlorophyll Biosynthetic Enzyme CHLI in Transgenic Tobacco.
In the present study, we have shown the transcriptional changes in a chlorosis model transgenic tobacco plant, i-amiCHLI, in which an artificial micro RNA is expressed in a chemically inducible manner to silence the expression of CHLI genes encoding a subunit of a chlorophyll biosynthetic enzyme. Comparison to the inducer-treated and untreated control non-transformants and untreated i-amiCHLI revealed that 3568 and 3582 genes were up- and down-regulated, respectively, in the inducer-treated i-amiCHLI plants. Gene Ontology enrichment analysis of these differentially expressed genes indicated the upregulation of the genes related to innate immune responses, and cell death pathways, and the downregulation of genes for photosynthesis, plastid organization, and primary and secondary metabolic pathways in the inducer-treated i-amiCHLI plants. The cell death in the chlorotic tissues with a preceding H2O2 production was observed in the inducer-treated i-amiCHLI plants, confirming the activation of the immune response. The involvement of activated innate immune response in the chlorosis development was supported by the comparative expression analysis between the two transgenic chlorosis model systems, i-amiCHLI and i-hpHSP90C, in which nuclear genes encoding different chloroplast proteins were similarly silenced.


Contrast-enhanced computed tomography scanning of the postoperative spine.
A prospective study of contrast-enhanced computed tomography (CT) scanning was undertaken for 17 levels previously operated upon in the lumbosacral spine in 14 patients. All levels with prior operations were scanned before and after the administration of intravenous contrast medium. A standardized technique for contrast enhancement using high doses of intravenous contrast medium was employed and a specialized technique for measuring enhancement with corrections for scan artifacts was used. Results indicated that measurable contrast enhancement occurred in 16 of 17 postoperative scars up to 12 years after surgery. Enhanced scans provided more accurate delineation of the size and margins of postoperative scarring than precontrast scans. No instances of enhancement of normal disk or recurrent herniated disk were observed. In six instances recurrent herniated disks were predicted on the basis of contrast-enhanced CT scans and subsequently confirmed at reoperation. Contrast-enhanced CT scans meticulously performed appear to permit differentiation between scarring and disk herniation in patients with recurring symptoms after operations for lumbosacral disk disease.


Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.
The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.


Assessment of afferent gut--brain function using cerebral evoked responses to esophageal stimulation.
Increasing awareness is attributed to altered sensory perception in the pathogenesis of gastrointestinal disorders. Evoked potentials (EP), which represent the brain's electrical response to peripheral stimulation, have recently been used to investigate where and how (GI) afferent information is processed along the brain-gut axis. EP can be obtained with electrical stimulation or balloon distention in the esophagus in humans. Stimulation of afferent neural pathways in the esophagus produces cerebral evoked responses allowing assessment of the peripheral afferent neural pathways involved, and of the function of integrative neural centers within the brain. Recent studies using esophageal EP indicate that the cerebral response to either mode of stimulation depends on the perception of the stimuli. Using electrical stimulation, a clear dose-response relationship is found. The EP response obtained with electrical stimulation is in keeping with those recorded using direct cervical stimulation of the vagus nerve, supporting evidence that esophageal EP are produced by activation of afferent vagal pathways. From the conduction velocity of the autonomic (vagal) nerves conveying information from esophagus to brain, it was concluded that non-painful electrical stimuli predominantly activate fast conducting myelinated afferent sensory fibers (A-fibers), while EP to balloon distention are largely due to activation of unmyelinated C-fibers. Techniques, however, vary widely amongst different investigators, and some electrophysiological parameters remain controversial, as there is no standard approach. Using balloon distention, EP waveforms vary widely between laboratories, suggesting that EP are substantially influenced by the stimulator devices (pump, respirator). EP to balloon distention are hampered by a relatively low signal-to-noise ratio (SNR), which is probably due to long inflation-deflation time (> 200 ms). With electrical stimulation, there is much less variability between different groups, and SNR is distinctly higher. This method appears to be most attractive for studies of afferent esophageal function. Standardization of the techniques is important, before esophageal EP can be regarded as a useful diagnostic approach in patient groups.


Episodic Memory Precision and Reality Monitoring Following Stimulation of Angular Gyrus.
The qualities of remembered experiences are often used to inform "reality monitoring" judgments, our ability to distinguish real and imagined events. Previous experiments have tended to investigate only whether reality monitoring decisions are accurate or not, providing little insight into the extent to which reality monitoring may be affected by qualities of the underlying mnemonic representations. We used a continuous-response memory precision task to measure the quality of remembered experiences that underlie two different types of reality monitoring decisions: self/experimenter decisions that distinguish actions performed by participants and the experimenter and imagined/perceived decisions that distinguish imagined and perceived experiences. The data revealed memory precision to be associated with higher accuracy in both self/experimenter and imagined/perceived reality monitoring decisions, with lower precision linked with a tendency to misattribute self-generated experiences to external sources. We then sought to investigate the possible neurocognitive basis of these observed associations by applying brain stimulation to a region that has been implicated in precise recollection of personal events, the left angular gyrus. Stimulation of angular gyrus selectively reduced the association between memory precision and self-referential reality monitoring decisions, relative to control site stimulation. The angular gyrus may, therefore, be important for the mnemonic processes involved in representing remembered experiences that give rise to a sense of self-agency, a key component of "autonoetic consciousness" that characterizes episodic memory.


Nucleic acid and antigen detection tests for leptospirosis.
Early diagnosis of leptospirosis may contribute to the effectiveness of antimicrobial therapy and early outbreak recognition. Nucleic acid and antigen detection tests have the potential for early diagnosis of leptospirosis. With this systematic review, we assessed the sensitivity and specificity of nucleic acid and antigen detection tests. To determine the diagnostic test accuracy of nucleic acid and antigen detection tests for the diagnosis of human symptomatic leptospirosis. We searched electronic databases including MEDLINE, Embase, the Cochrane Library, and regional databases from inception to 6 July 2018. We did not apply restrictions to language or time of publication. We included diagnostic cross-sectional studies and case-control studies of tests that made use of nucleic acid and antigen detection methods in people suspected of systemic leptospirosis. As reference standards, we considered the microscopic agglutination test alone (which detects antibodies against leptospirosis) or in a composite reference standard with culturing or other serological tests. Studies were excluded when the controls were healthy individuals or when there were insufficient data to calculate sensitivity and specificity. At least two review authors independently extracted data from each study. We used the revised Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) to assess risk of bias. We calculated study-specific values for sensitivity and specificity with 95% confidence intervals (CI) and pooled the results in a meta-analysis when appropriate. We used the bivariate model for index tests with one positivity threshold, and we used the hierarchical summary receiver operating characteristic model for index tests with multiple positivity thresholds. As possible sources of heterogeneity, we explored: timing of index test, disease prevalence, blood sample type, primers or target genes, and the real-time polymerase chain reaction (PCR) visualisation method. These were added as covariates to the meta-regression models. We included 41 studies evaluating nine index tests (conventional PCR (in short: PCR), real-time PCR, nested PCR, PCR performed twice, loop-mediated isothermal amplification, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, immunochromatography-based lateral flow assay, and dipstick assay) with 5981 participants (1834 with and 4147 without leptospirosis). Methodological quality criteria were often not reported, and the risk of bias of the reference standard was generally considered high. The applicability of findings was limited by the frequent use of frozen samples. We conducted meta-analyses for the PCR and the real-time PCR on blood products.The pooled sensitivity of the PCR was 70% (95% CI 37% to 90%) and the pooled specificity was 95% (95% CI 75% to 99%). When studies with a high risk of bias in the reference standard domain were excluded, the pooled sensitivity was 87% (95% CI 44% to 98%) and the pooled specificity was 97% (95% CI 60% to 100%). For the real-time PCR, we estimated a summary receiver operating characteristic curve. To illustrate, a point on the curve with 85% specificity had a sensitivity of 49% (95% CI 30% to 68%). Likewise, at 90% specificity, sensitivity was 40% (95% CI 24% to 59%) and at 95% specificity, sensitivity was 29% (95% CI 15% to 49%). The median specificity of real-time PCR on blood products was 92%. We did not formally compare the diagnostic test accuracy of PCR and real-time PCR, as direct comparison studies were lacking. Three of 15 studies analysing PCR on blood products reported the timing of sample collection in the studies included in the meta-analyses (range 1 to 7 days postonset of symptoms), and nine out of 16 studies analysing real-time PCR on blood products (range 1 to 19 days postonset of symptoms). In PCR studies, specificity was lower in settings with high leptospirosis prevalence. Other investigations of heterogeneity did not identify statistically significant associations. Two studies suggested that PCR and real-time PCR may be more sensitive on blood samples collected early in the disease stage. Results of other index tests were described narratively. The validity of review findings are limited and should be interpreted with caution. There is a substantial between-study variability in the accuracy of PCR and real-time PCR, as well as a substantial variability in the prevalence of leptospirosis. Consequently, the position of PCR and real-time PCR in the clinical pathway depends on regional considerations such as disease prevalence, factors that are likely to influence accuracy, and downstream consequences of test results. There is insufficient evidence to conclude which of the nucleic acid and antigen detection tests is the most accurate. There is preliminary evidence that PCR and real-time PCR are more sensitive on blood samples collected early in the disease stage, but this needs to be confirmed in future studies.


[Influence of soluble carbon and nitrogen on ammonia volatilization from different thermal zones soil].
A static absorption method was used to study the influence of soluble carbon and nitrogen on ammonia volatilization from different thermal zone soils, such as black soil, red soil and cinnamon soil, performed in laboratory. Results showed that nitrogen application enhanced ammonia volatilization significantly. The amount of ammonia volatilization in cinnamon soil ranged from 14.3 to 7.37 mg x kg(-1), which in black soil from 1.52 to 1.11 mg x kg(-1) and from 0.998 to 0.402 mg x kg(-1) in red soil applied with only nitrogen or nitrogen amended with soluble carbon. Moreover, soluble carbon decreased ammonia volatilization caused by nitrogen, and amounts of decrease were 27.0%, 48.5%, 60.0% in black soil, cinnamon soil and red soil separately. The amount of ammonia volatilization from black soil and cinnamon soil applied only nitrogen was in an order of CK > NPK > NPKOM, while contrary order appeared if nitrogen was amended with soluble carbon. However, it was the same order for red soil applied with only nitrogen or nitrogen amended with soluble carbon. In addition, the variances of NH4+ -N and NO3- -N contents in cinnamon soil were larger than other soils, which suggested that cinnamon soil had high potential of nitrogen loss.


Relaxing radial retinal incisions for the treatment of persistent macular holes.
Various surgical techniques have been described for managing persistent macular holes after an unsuccessful vitrectomy with internal limiting membrane (ILM) peeling. However, the closure and functional improvement rates after these procedures are limited. Therefore, the aim of this study was to evaluate the usefulness of radial retinal incisions (retinotomies) in eyes with persistent large macula holes despite previous vitrectomy with ILM peeling. In a retrospective case series, closure rate and best-corrected visual acuity (BCVA) were evaluated in eyes with persistent macular holes after an unsuccessful vitrectomy that included posterior vitreous detachment and ILM peeling. 22 eyes of 22 patients (10 men and 12 women) underwent re-vitrectomy with radial retinal incisions. All the patients had undergone an unsuccessful surgery before. Small-incision re-vitrectomy with radial retinal incisions (retinotomies) and air tamponade was performed. For all eyes, high-definition SD-OCT scans (SD-OCT Spectralis, Heidelberg Engineering GmbH, Germany) of the macula were routinely performed before surgery; 1 week and 1 month after surgery; and at final follow-up. Additionally, age, gender, axial length, macular hole diameter, biomicroscopic fundus evaluation and best-corrected visual acuity (BCVA) in logMAR and Snellen at baseline, 1 and 4 months after operation, and at the final follow-up visit were analyzed. The mean baseline macular hole diameter was 668.5 ± 226.8 μm. At the final examination, 16 (72.72%) of the 22 macula holes were closed. Visual acuity increased in 17 eyes, was stable in 3 eyes, and decreased in 2 eyes owing to central retinal atrophy in both. The mean BCVA increased from logMAR 1.04 ± 0.29 at baseline to 0.57 ± 0.31 (Snellen 0.11 ± 0.05 to 0.33 ± 0.18). In all successful cases, macula hole closure was attained after 3 days, and none of the eyes showed macula hole recurrence. The results of this limited case series suggest that radial retinal incisions of the rim in persistent macula holes after initial surgery with ILM peeling increase the success rate of macula hole closure and results in a relevant increase in BCVA. However, as the number of eyes included in this series is limited, the results must be confirmed in a study with a larger sample size.


Neurofilaments from ox spinal nerves. Isolation, disassembly, reassembly and cross-linking properties.
An isolation procedure for neurofilaments from ox spinal nerves is described where the triplet polypeptides (which have molecular weights of 205 000, 158 000 and 72 000) constitute more than 80% of the preparation. Soon after purification, the neurofilaments form a gel that is stable for many weeks. The purified neurofilaments disassemble in low-salt buffers at pH greater than 7.0 into soluble particles that contain all of the triplet polypeptides. Greater than 90% of the protein can reassemble to form filaments. The thiol-containing residues in the filaments can be cross-linked. Analyses of the complexes formed show that in the filament the 205 000-mol.wt. components are arranged to that they can be cross-linked to themselves and to the 158 000-mol.wt. polypeptides, and that the 72 000-mol.wt. components are arranged so that their thiol groups can be cross-linked together.


Vital signs: seat belt use among long-haul truck drivers--United States, 2010.
Motor vehicle crashes were the leading cause of occupational fatalities in the United States in 2012, accounting for 25% of deaths. Truck drivers accounted for 46% of these deaths. This study estimates the prevalence of seat belt use and identifies factors associated with nonuse of seat belts among long-haul truck drivers (LHTDs), a group of workers at high risk for fatalities resulting from truck crashes. CDC analyzed data from its 2010 national survey of LHTD health and injury. A total of 1,265 drivers completed the survey interview. Logistic regression was used to examine the association between seat belt nonuse and risk factors. An estimated 86.1% of LHTDs reported often using a seat belt, 7.8% used it sometimes, and 6.0% never. Reporting never using a belt was associated with often driving ≥10 mph (16 kph) over the speed limit (adjusted odds ratio [AOR] = 2.9), working for a company with no written safety program (AOR = 2.8), receiving two or more tickets for moving violations in the preceding 12 months (AOR = 2.2), living in a state without a primary belt law (AOR = 2.1); and being female (AOR = 2.3). Approximately 14% of LHTDs are at increased risk for injury and death because they do not use a seat belt on every trip. Safety programs and other management interventions, engineering changes, and design changes might increase seat belt use among LHTDs. Primary state belt laws can help increase belt use among LHTDs. Manufacturers can use recently collected anthropometric data to design better-fitting and more comfortable seat belt systems.


Further studies on the heat-stability of freeze-dried glutamate BCG vaccine: Effect of storage at 30 degrees -50 degrees C on allergenic potency in humans.
In order to avoid the necessity for continuous refrigeration of liquid BCG vaccine during storage and transport in hot climates, various attempts have been made to develop more stable preparations. Several studies have indicated that freeze-dried BCG vaccines, and in particular the Japanese glutamate vaccine, are more resistant to high temperatures than liquid BCG vaccines. The present paper reports the results of three studies in schoolchildren designed to compare the heat-stability of three dried vaccines (Japanese glutamate vaccine, Japanese sucrose vaccine, and French glucose vaccine) and Danish liquid vaccine. The results showed that the allergenic potency of the Japanese glutamate vaccine was not much reduced even after storage at 42 degrees C for one month whereas the liquid vaccine was already seriously damaged after one month's storage at 30 degrees C. Exposure to a temperature of 50 degrees C for one month was found to reduce the allergenic capacity of all three freeze-dried vaccines. As exposure to such high temperatures hardly ever occurs under field conditions, it seems probable that the dried glutamate vaccine can be used without refrigeration even in tropical countries. However, the duration of the allergy induced by the heat-treated glutamate vaccine has not yet been definitely established. This question is under further study.


Afforestation and climate mitigation: lessons from Chile.
The Chilean Climate Change Law excludes tree monocultures as a solution to the climate crisis, offering an opportunity for resilience and climate mitigation in Latin America. The Chilean experience with mega-fires in extensive, homogeneous forest plantations provides important lessons that could inform climate policies in other countries.


Anatomical Variations of the Blood Vascular System in Veterinary Medicine: The Internal Iliac Artery of the Dog - Part Three.
The aim of this study was to analyse and describe the variability of the umbilical artery. Two hundred and thirty-two pelvic halves from 116 adult dogs were examined. To study the permeability of the umbilical artery, ten adult dogs, nine newborns and thirteen foetuses between 35 and 50 days of gestation were also used. In relation to the origin of the umbilical artery, six anatomical variations were found. From which five involved a cranial (n = 4) or caudal (n = 1) relocation of its origin, and in one case (n = 1), the umbilical artery arose from the median sacral artery. In eight cases, the umbilical artery gave off the prostatic (n = 1) or vaginal (n = 7) arteries. The permeability of the umbilical artery was the most significant anatomical variation: permeability was detected in 45% (106 of 232 pelvic halves) of all cases, from which 36 were males and 70 females. Interestingly, an equal vascular permeability in both hemipelvises was found for 82% of the dogs, thus additional data related to such feature of the umbilical artery was also recorded. In accordance with the statistical study, the main anatomical variations described showed significant values for gender, side of the body, size and profile variables.


[Basic studies for the development of anticancer, antidementia, and taste modifier drugs].
We developed various types of differentiation- and apoptosis-inducing agents against tumor cells and also studied the function and structure of synucleins and taste modifiers. Differentiation- and apoptosis-inducing agents are classified into DNA-damaging agents, Na(+), K(+)-ATPase inhibitors, agents affecting the redox states of tumor cells, agents affecting signal transduction pathways, isoprenoid compounds, and ATP-noncompetitive tyrosine kinase inhibitors. These include camptothecin, etoposide, cisplatin, transplantin, bufalin, arsenic trioxide, costunolide, C(2)- ceramide, daidzein, geranylgeranylacetone, geranylgeraniol, vitamin K(2), sophoranone, and beta-hydroxyisovalerylshikonin. The mechanisms of action of these differentiation- and apoptosis-inducing agents are described. The structure and function of synucleins are also reviewed for the development of potential antidementia agents. In addition, the structures of three purified taste modifiers are described.