Transient Improvement of Cerebellar Oligodendroglial Development in a Neonatal Hyperoxia Model by PDGFA Treatment.
In preterm infants, the changes from fetal life to ex-utero conditions often coincide with reduced growth and white matter damage of the cerebellum. The premature increase in arterial oxygen tension caused by preterm birth may dysregulate cerebellar development. In a hyperoxia rat model of white matter damage to mimic a steep increase in oxygen levels by 24 h exposure to 80% O2 from postnatal day 6 (P6) to day 7, we analyzed growth factor (GF) synthesis of cerebellar astrocytes. Determination of GF production was performed in astrocytes after Magnetic-activated cell sorting (MACS) isolation from cerebelli after hyperoxia exposure ex vivo, and also in astroglial cultures. Oligodendrocyte progenitor cell (OPC) function was analyzed in cerebellar OPCs isolated by MACS after hyperoxia. Administration of PDGFA from P6 to P11, during hyperoxia and during 4 days recovery, was finally tested for protection of oligodendroglia and myelination. As a result, expression of the GFs Pdgfa, Fgf2, and Bdnf was diminished in cerebellar astrocytes in vitro and in vivo. Gene expression of Olig1, Olig2, Sox9, Sox10, and Cnp was reduced in OPCs in vivo. Nasal PDGFA application improved oligodendroglial proliferation after hyperoxia at P7. However, this treatment effect vanished until P9. Impaired MBP expression after hyperoxia was attenuated by PDGFA treatment until P11, but not beyond when PDGFA supply was stopped. In this study on neonatal cerebellar injury, it is documented for the first time that improvement of oligodendroglial proliferation and of myelination can be achieved by PDGFA treatment. However, the treatment benefit is not maintained long term.


Dissection of the peripheral motion channel in the visual system of Drosophila melanogaster.
In the eye, visual information is segregated into modalities such as color and motion, these being transferred to the central brain through separate channels. Here, we genetically dissect the achromatic motion channel in the fly Drosophila melanogaster at the level of the first relay station in the brain, the lamina, where it is split into four parallel pathways (L1-L3, amc/T1). The functional relevance of this divergence is little understood. We now show that the two most prominent pathways, L1 and L2, together are necessary and largely sufficient for motion-dependent behavior. At high pattern contrast, the two pathways are redundant. At intermediate contrast, they mediate motion stimuli of opposite polarity, L2 front-to-back, L1 back-to-front motion. At low contrast, L1 and L2 depend upon each other for motion processing. Of the two minor pathways, amc/T1 specifically enhances the L1 pathway at intermediate contrast. L3 appears not to contribute to motion but to orientation behavior.


Transplantability of naturally occurring benign and malignant neoplasms and age-associated nonneoplastic lesions of the aging F344 rat as biological evidence for the histological diagnosis of neoplasms.
Portions of 162 naturally occurring neoplasms and 26 nonneoplastic lesions from 93 aged male or female F344/NCr rats were implanted into the left inguinal mammary fat pads of weanling syngeneic recipients. As controls, 95 normal tissues were implanted to the right inguinal fat pad. Transplant recipients were maintained for up to 1 year. Essentially, all types of naturally occurring benign and malignant tumors were successfully transplanted, i.e., grew progressively forming nodules and masses. For the transplants, the latency period preceding palpable growth, tumor growth rate, invasiveness, metastatic rate, and time to death were associated with the degree of histological malignancy of the primary tumor. The tumors which were the most malignant based on these criteria included large granular lymphocyte leukemia, sarcomas, and carcinomas. Fibromas, mammary fibroadenomas, and papillomas were easily transplanted but were not invasive. Endocrine tumors generally were the slowest-growing tumors. This study provides evidence that successful tumor transplantation is only evidence of neoplasia and does not distinguish whether a primary tumor is benign or malignant.


America COMPETES at 5 years: An Analysis of Research-Intensive Universities' RCR Training Plans.
This project evaluates the impact of the National Science Foundation's (NSF) policy to promote education in the responsible conduct of research (RCR). To determine whether this policy resulted in meaningful RCR educational experiences, our study examined the instructional plans developed by individual universities in response to the mandate. Using a sample of 108 U.S. institutions classified as Carnegie "very high research activity", we analyzed all publicly available NSF RCR training plans in light of the consensus best practices in RCR education that were known at the time the policy was implemented. We found that fewer than half of universities developed plans that incorporated at least some of the best practices. More specifically, only 31% of universities had content and requirements that differed by career stage, only 1% of universities had content and requirements that differed by discipline; and only 18% of universities required some face-to-face engagement from all classes of trainees. Indeed, some schools simply provided hand-outs to their undergraduate students. Most universities (82%) had plans that could be satisfied with online programs such as the Collaborative Institutional Training Initiative's RCR modules. The NSF policy requires universities to develop RCR training plans, but provides no guidelines or requirements for the format, scope, content, duration, or frequency of the training, and does not hold universities accountable for their training plans. Our study shows that this vaguely worded policy, and lack of accountability, has not produced meaningful educational experiences for most of the undergraduate students, graduate students, and post-doctoral trainees funded by the NSF.


Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial.
Perioperative administration of pregabalin, which is effective for neuropathic pain, might reduce early postoperative and chronic pain. This randomized, double-blinded, placebo-controlled trial (Clinical Trials.gov ID NCT00905580) was designed to investigate the efficacy and safety of pregabalin for reducing both acute postoperative pain and the development of chronic pain in patients after robot-assisted endoscopic thyroidectomy. Ninety-nine patients were randomly assigned to groups that received pregabalin 150 mg or placebo 1 h before surgery, with the dose repeated after 12 h. Assessments of pain and side effects were performed 48 h postoperatively. The incidences of chronic pain and hypoesthesia in the anterior chest were recorded 3 months after surgery. Ninety-four patients completed the study. Verbal numerical rating scale scores for pain and the need for additional analgesics were lower in the pregabalin group (n = 47) than the placebo group (n = 47) during 48 h postoperatively (P < 0.05). However, incidences of sedation and dizziness were higher in the pregabalin group (P < 0.05). There were no differences between the groups in the incidences of chronic pain and chest hypoesthesia at 3 months after surgery. Perioperative administration of pregabalin (150 mg twice per day) was effective in reducing early postoperative pain but not chronic pain in patients undergoing robot-assisted endoscopic thyroidectomy. Caution should be taken regarding dizziness and sedation.


Temperature distributions in tumor models heated by self-regulating nickel-copper alloy thermoseeds.
Needle-shaped thermoseeds have been manufactured from an alloy consisting of 70.4% nickel and 29.6% copper. The magnetic properties of the alloy were measured at various temperatures and from this the heating power produced by a thermoseed exposed to an electromagnetic induction field was computed as a function of the seed temperature. Calorimetric measurements were also performed. From these data, temperature distributions in simple tumor models assumed to be heated by an array of nickel-copper implants were computed. It was found that the nickel-copper implants produce substantially better temperature homogeneity than readily available constant power seeds, especially in tumors with unpredictable rates of blood perfusion or when the implant arrangement is not perfectly regular. Since such conditions are likely to be present in actual patients, the nickel-copper implants should be very useful in clinical hyperthermia.


Neurovascular responses to sequential deep inspirations assessed via laser-Doppler perfusion changes in dorsal finger skin.
A vasomotor reflex triggered by a rapid and deep inspiration causes arteriolar vasoconstriction and a transient decrease in skin blood flow in most people. This is the inspiratory gasp vascular response (IGVR). The most common site of its measurement has been on the palmar or plantar aspect of the digits and little is known about its features in skin with few or any arterial venous anastomoses (AVAs). A basic aspect of this response that has not been systematically studied is its associated with multiple sequential inspiratory gasps (IG) in the same person. Such information would provide insight as to whether there is any form of adaptation or temporal dependence and may serve as a basis for judging response variability. Thus, the present study was undertaken to characterize the normal pattern of responses in finger dorsum skin in a group of 28 normal persons who performed 21 sequential, uniformly spaced IG, over an interval of 42 min. The results show that IGVR measured on the finger dorsum have a magnitude comparable with that obtained on finger pulp, in spite of the relative dearth of sympathetically controlled AVAs on the dorsum. It was also found that the magnitude of the IGVR displays little if any tendency for sequential adaptation or temporal trending. Finally, the results indicate that the largest component of response variability is associated with subject-to-subject differences as compared with sequential variability within subjects.


Serum HDL-cholesterol in women using low dose oral contraceptives.
This study was done to appraise the effects of low-dose oral contraceptives (OCs) containing 30microgm ethinyl estradiol and 150microgm levonorgestrel on lipid metabolism by a lipid variable-serum HDL-cholesterol (HDL-C). HDL-C has been identified as a lipoprotein that protects against atherosclerosis and its levels are inversely proportional to the risk for developing ischemic coronary disease and venous thromboembolic disorders. Ninety young women within reproductive age group were picked for this study. Sixty women using low-dose oral contraceptives served as experimental group and thirty age matched hormonal contraceptive non users were selected for control group. Experimental group was again subdivided into OCs users for last one-year group, three-year group and five-year group. The result showed that there was no significant difference on serum HDL-cholesterol levels between users & non-users women. It is concluded that low-dose oral contraceptives regimens did not significantly affect the lipid metabolism. It can be safely used as contraceptive & non-contraceptive purposes. The value of studied parameter for serial longer duration of OCs uses needs to be assessed.


PATIENTS EXPERIENCES OF INVOLVEMENT IN CHOICE OF DIALYSIS MODE.
International guidelines recommend that patients choose dialysis mode based on their own values and preferences; thus, involvement is needed in dialysis choice. A literature review indicated a lack of knowledge concerning patient involvement in decision-making, especially concerning patients' experiences of the decision-making process just after making the decision and before starting dialysis. To gather information about how patients experienced involvement in the decision-making process of renal substation therapy just after they have made the decision and before starting dialysis. A qualitative method with a phenomenological and hermeneutic approach. The study was based on individual semi-structured interviews with nine adult patients with chronic kidney disease. A data-driven analysis based on systematic text condensation was used. Patients are a significant part of the decision. Health care professionals contribute to the experience of being involved. Patients keep putting off the final choice. The patients found themselves involved in the choice of dialysis mode and have different views on what is needed to feel being involved. Information, interaction, and advice from health care professionals affect this experience. However, the experience of not having any symptoms caused patients to put off the final choice of dialysis mode.


Material analysis end-station of the Hyogo-ken beamline at SPring-8.
Plans to construct surface-analysis equipment which will be placed on beamline BL24XU of SPring-8 are presented. There are three experimental hutches in BL24XU, which are available simultaneously by using diamond monochromators as beam splitters. The purpose of the surface-analysis equipment is the simultaneous measurement of fluorescent and diffracted X-rays in grazing-incidence geometry. The instrument is equipped with a solid-state detector (SSD) and a flat position-sensitive proportional counter (PSPC) combined with analysing crystals for X-ray fluorescence (XRF) analysis. A curved PSPC and the goniometer that mounts the SSD used for XRF are also installed for X-ray diffraction. X-ray fluorescence holography and polarized X-ray emission spectroscopy modes are available, so three-dimensional images of atomic configurations and also the anisotropic structure of materials will be studied.


Woody species diversity, population structure, and regeneration status in the Gra-Kahsu natural vegetation, southern Tigray of Ethiopia.
The study was conducted at Gra-Kahsu protected natural vegetation (PNV) and communal grazing land (CGL), in order to evaluate the conservation impact level. The diversity of plant species, population structure of woody species, and regeneration status were analysed from 62 quadrats, each with 20 m × 20 m for trees and 5 m × 5 m for shrubs, using systematic sampling methods. A total of 64 vascular plant species belonging to 52 genera and 37 families from PNV and 43 plant species belonging to 34 genera and 25 families from CGL was identified. Shannon diversity index values of PNV and CGL were 2.29 and 1.84, respectively. The mean basal area of PNV and CGL were 8.29 and 5.32 m2/ha, respectively. Three community types from PNV and two from CGL were identified. The population structure of woody species based on diameter and height class distribution showed reflected reversed J-shape for PNV however, bell-shaped, and interrupted inverted J-shape for CGL. The regeneration status of PNV and CGL were considered as good (sapling > seedling > matures) and fair (mature > sapling > seedling), respectively. Therefore, the floristic analysis of these two adjacent land use systems located in similar landscape showed distinctive variation in floristic composition, diversity, and regeneration status, which could be taken as the best practice of restoration and rehabilitation programs like, area exclosure.


Gynecologists' sex, clinical beliefs, and hysterectomy rates.
This study determined how gynecologists' sex, beliefs, appropriateness ratings, and practice characteristics influence hysterectomy rates in North Carolina. Gynecologists who performed hysterectomies at higher rates were further from training, practiced in areas with fewer gynecologists, and had more patients with abnormal bleeding or cancer. Male gynecologists performed 60% more hysterectomies than female gynecologists, but this may have been because they were further from their training. Appropriateness ratings were affected by gynecologists' attitudes toward surgery, recency of training, and practice case mix, and by patients' expressed desire to avoid surgery, but they did not predict hysterectomy rates. To decrease their chances of undergoing hysterectomy, patients should express their preferences and possibly seek the opinion of more recently trained gynecologists.


The use of synthetic peptides in the study of experimental autoimmune uveitis.
S-antigen is a highly pathogenic retinal autoantigen for the induction of experimental autoimmune uveitis (EAU). EAU is predominantly a T cell mediated autoimmune disease of the uveal tract and retina of the eye and the pinealocytes of the pineal gland. Using synthetic peptides it has been possible to identify several B cell and T cell epitopes in the molecule. In addition, synthetic peptides derived from proteins of diverse origin with amino acid sequence homology to pathogenic regions of S-antigen induce an EAU which is indistinguishable from the disease induced by native S-antigen. These studies aid in the understanding of immune mechanisms in EAU and provide a basis for the pathogenesis of uveitis in humans.


[Professor Drago Vrbanić - the important contribution to the development of oncology in Rijeka].
In Rijeka of the 1950s professor Drago Vrbanić was well-known as an excellent gynaecologist and surgeon, especially in the field of gynaecological malignant tumours. He headed the gynaecological and radiology departments of the Sobol Brothers General Hospital, and successfully applied several radiotherapy methods. Later in the 1960s, he introduced modern classification of tumours and multidisciplinary expertise in the diagnostics and treatment of gynaecological cancers. He combined a variety of operation procedures and methods with modern radiotherapy, significantly improving the results of malignant tumour therapy.


Angular color shift of micro-LED displays.
Sidewall emission of a micro-scale light emitting diode (micro-LED) improves the light extraction efficiency, but it causes mismatched angular distributions between AlGaInP-based red micro-LED and InGaN-based blue/green counterparts due to material difference. As a result, color shift of RGB micro-LED displays may become visually noticeable. To address this issue, we first analyze the angular distributions of RGB micro-LEDs and obtain good agreement between simulation and experiment. Next, we propose a device structure with top black matrix and taper angle in micro-LEDs, which greatly suppresses the color shift while keeping a reasonably high light extraction efficiency.


Abundance and diversity of ammonia-oxidizing archaea and bacteria in the rhizosphere soil of three plants in the Ebinur Lake wetland.
Ammonia oxidation is carried out by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA). The Ebinur Lake wetland is the best example of a temperate arid zone wetland ecosystem in China. Soil samples were collected from rhizosphere and non-rhizosphere soil containing Halocnemum strobilaceum (samples H and H'), Phragmites australis (samples R and R'), and Karelinia caspia (samples K and K') to study the relationship between environmental factors and the community structure of AOB and AOA. Phylogenetic analysis showed that the AOA sequences belonged to the Nitrosopumilus and Nitrososphaera clusters. AOB were grouped into Nitrosospira sp. and Nitrosomonas sp. Quantitative polymerase chain reaction results showed that the AOA abundance ranged from 2.09 × 104 to 2.94 × 105 gene copies/g soil. The highest number of AOA was detected in sample K, followed by samples R and H. AOB abundance varied between 2.91 × 105 and 1.05 × 106 gene copies/g soil, which was higher than that of AOA. Redundancy analysis indicated that electrical conductivity, pH, and NH4+-N might influence the community structure of AOA and AOB. AOB might play a more crucial role than AOA in ammonia oxidation based on AOB's higher diversity and abundance in the Ebinur Lake wetland in Xinjiang.


Space Compositional Aspects Regarding the Importance of Trees in the Urban Landscape.
Individual trees and tree compositions provide a wide range of cultural ecosystem services, including playing a key role in defining urban character. In Hungary, urban landscape protection tools have recently been expanded, bringing the topic into the spotlight. However, the significance of natural elements (and particularly trees) in relation to the urban landscape is still under-researched. In this paper, using a novel methodology, the character-forming significance of trees and tree-compositional elements of historic gardens in Hungary that define the urban character is analysed and evaluated. The urban landscape protection tools that establish the current recognition of green elements within the urban landscape are also analysed. In addition, the spatial situations and characteristics making certain trees in historic gardens defining character elements within Hungarian settlements are studied. Reasons behind the lack of significant tree features in certain historic gardens, as well as the external and internal characteristics of tree elements that determine their visual impact have been categorised. The results reveal that visually important trees, while diverse, show distinct trends in terms of visibility and are subject to constant change. The results imply that a paradigm shift is necessary to maintain, design and regulate green infrastructure in relation to visually important trees.


Barriers to accessing and using contraception in highland Guatemala: the development of a family planning self-efficacy scale.
Understanding the persistent inequalities in the prevalence rates of family planning and unmet need for family planning between indigenous and nonindigenous women in Guatemala requires localized explorations of the specific barriers faced by indigenous women. Based on social cognitive theory, elicitation interviews were carried out with a purposive sample of 16 young women, aged 20-24 years, married or in union, from the rural districts of Patzún, Chimaltenango, Guatemala. Content analysis was carried out using the constant-comparison method to identify the major themes. Based on this qualitative study, the following barriers are incorporated into the development of a self-efficacy scale: lack of knowledge about and availability of methods, fear of side effects and infertility, husbands being against family planning (and related fears of marital problems and abandonment), pressure from in-laws and the community, and the belief that using contraception is a sin. This is the first evidence-informed self-efficacy scale developed with young adult, indigenous women that addresses the issue of family planning in Latin America.


Low-beta cortico-pallidal coherence decreases during movement and correlates with overall reaction time.
Beta band oscillations (13-30 Hz) are a hallmark of cortical and subcortical structures that are part of the motor system. In addition to local population activity, oscillations also provide a means for synchronization of activity between regions. Here we examined the role of beta band coherence between the internal globus pallidus (GPi) and (motor) cortex during a simple reaction time task performed by nine patients with idiopathic dystonia. We recorded local field potentials from deep brain stimulation (DBS) electrodes implanted in bilateral GPi in combination with simultaneous whole-head magneto-encephalography (MEG). Patients responded to visually presented go or stop-signal cues by pressing a button with left or right hand. Although coherence between signals from DBS electrodes and MEG sensors was observed throughout the entire beta band, a significant movement-related decrease prevailed in lower beta frequencies (∼13-21 Hz). In addition, patients' absolute coherence values in this frequency range significantly correlated with their median reaction time during the task (r = 0.89, p = 0.003). These findings corroborate the recent idea of two functionally distinct frequency ranges within the beta band, as well as the anti-kinetic character of beta oscillations.


[Pathophysiology and epidemiology of listeriosis].
Listeriosis is a severe infectious disease occurring both in humans and in most other animal species. It is caused by a Gram-positive bacterium, Listeria monocytogenes. This facultative intracellular pathogen is widespread in nature and infects humans through contaminated food. After ingestion, bacteria can cross the gut mucosa and disseminate via the bloodstream. They may then invade the central nervous system and the placenta, causing severe meningoencephalitis and fetoplacental infections, respectively. The mortality rate is about 30%, despite antibiotic therapy. Listeriosis offers an excellent model for studying how bacterial pathogens can cross the blood-brain barrier and placenta. Our understanding of the molecular mechanisms of intracellular parasitism and dissemination to host tissues is better for L. monocytogenes than for any other bacterial pathogen.


High precision mass measurements for wine metabolomics.
An overview of the critical steps for the non-targeted Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-ToF-MS) analysis of wine chemistry is given, ranging from the study design, data preprocessing and statistical analyses, to markers identification. UPLC-Q-ToF-MS data was enhanced by the alignment of exact mass data from FTICR-MS, and marker peaks were identified using UPLC-Q-ToF-MS(2). In combination with multivariate statistical tools and the annotation of peaks with metabolites from relevant databases, this analytical process provides a fine description of the chemical complexity of wines, as exemplified in the case of red (Pinot noir) and white (Chardonnay) wines from various geographic origins in Burgundy.


[Bruch's Membrane Opening in OCT in Correlation with Corneal Correction - a Pilot Study].
Background: The measurement by optical coherence tomography (OCT) of the Bruch membrane opening (BMO) and the thinnest retinal fiber nerve layer in relation to it (BMO-MRW) has been performed in clinical routine since 2014. To compensate for astigmatism, or increased or decreased corneal power, a correction is performed through the mean K-value of the measured eye. The aim of this study was to measure the value of this correction and its influence on the measurement results. Methods: The sectors of BMO-MRW and BMO values of the five right eyes of five healthy patients were measured five times each with Heidelberg Spectralis OCT. Corneal compensation was systematically raised with each single measurement (7.1, 7.4, 7.7, 8.0, 8.3 mm). The data showed almost linear dependence on the given corneal compensation values, with intraindividual variability. For the BMO-MRW, only small effects of compensation were found (0.85 up to 1.97 % per K-value difference of 0.3 mm). For BMO, the effect was greater, with a mean change of 7.71 % for every 0.3 mm change in compensation. Conclusion: For BMO-MRW, corneal compensation is of low clinical relevance. BMO is more dependent on this correction. In follow-up measurements, the compensation might not account for significant changes, although we recommend using correct corneal compensation values when obtaining single or first-time measurements.


Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study.
High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study. The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty-four healthy subjects matched for age and sex formed the group control. Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p<0.001). Using previously reported cut off values (>150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009). Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.


Treatment of Crohn's disease in relapse with cyclosporin A.
It has been suggested that cyclosporin A might be of some benefit to patients with Crohn's disease. The clinical response and side-effects of cyclosporin A in Crohn's disease are described in a series of 13 adults. The majority of patients had ileal disease and all but one were started on an initial oral dose of 15 mg/kg per day. Duration of treatment ranged from 3 to 42 weeks. Of the 13 patients, 6 showed a response to therapy; the remainder showed no response or deteriorated. The commonest side-effect was hyperaesthesia, but one patient developed nephrotoxicity and one developed hepatotoxicity. Significant drug malabsorption occurred in one case. The side-effects were dose dependent and reversible. Cyclosporin A may have a part to play in the treatment of resistant Crohn's disease, and in our hands has been associated with a 46 per cent response rate; however, the precise role of cyclosporin A in the management of Crohn's disease awaits further study.


An examination of the factor structure of the Millon Clinical Multiaxial Inventory.
This study involved a comparison of the factor structure of the MCMI in: a general psychiatric sample, a substance misuse sample, and a drug misuse sample. Examination of the factor matrices for the three clinical samples provided evidence for a sturdy factor measuring a negativistic-avoidant personality style with associated anxiety, depression, and somatization. Evidence was also available in all three samples for factors measuring: a) a paranoid cognitive and interpersonal pattern, and b) an asocial-avoidant personal orientation.


Impact of brain natriuretic peptide reduction on the worsening renal function in patients with acute heart failure.
The prognostic impact of worsening renal function (WRF) in patients with acute heart failure (AHF) remains under debate. Successful decongestion might offset the negative impact of WRF, but little is known about indicators of successful decongestion in the very acute phase of AHF. We hypothesized that decongestion as evaluated by the percent reduction in brain natriuretic peptide (BNP) could identify relevant prognostic implications of WRF in the very acute phase of AHF. Data on 907 consecutive hospitalized patients with AHF in the REALITY-AHF study (age: 78±12 years; 55.1% male) were analyzed. Creatinine and BNP were measured at baseline and 48 hours from admission. WRF was defined as an increase in creatinine >0.3 mg at 48 hours from admission. The primary endpoint was 1-year all-cause mortality. Patients were divided into four groups according to the presence/absence of WRF and a BNP reduction higher/lower than the median: no-WRF/higher-BNP-reduction (n = 390), no-WRF/lower-BNP-reduction (n = 397), WRF/higher-BNP-reduction (n = 63), and WRF/lower-BNP-reduction groups (n = 57). Kaplan-Meier curve analysis showed that the WRF/lower-BNP-reduction group had a worse prognosis than the other groups. In a Cox regression analysis, only the WRF/lower-BNP-reduction group had higher mortality compared to the no-WRF/higher-BNP-reduction group (hazard ratio: 3.34, p<0.001). In the very acute phase of AHF, BNP reduction may aid in identifying relevant prognostic significance of WRF.


FAILURE OF ARSENATE TO UNCOUPLE THE PHOSPHOTRANSACETYLASE SYSTEM IN CLOSTRIDIUM ACIDIURICI.
Sagers, Richard D. (Brigham Young University, Provo, Utah), Moshe Benziman, and Sigrid M. Klein. Failure of arsenate to uncouple the phosphotransacetylase system in Clostridium acidiurici. J. Bacteriol. 86:978-984. 1963.-The conversion of pyruvate to acetyl phosphate by extracts of Clostridium acidiurici required coenzyme A (CoA), an electron-carrier system (ferredoxin and nicotinamide adenine dinucleotide), and a divalent metal. Other cofactors may be involved but are not presently defined. The metal activates the system transferring acetyl units between CoA and phosphate. Acetyl CoA could be generated from pyruvate or from acetyl phosphate, but in both cases arsenate failed to uncouple the high-energy acyl compounds. The rate of acetyl transfer between acetyl phosphate and CoA was markedly decreased by 0.005 m arsenate, but the generation of acetyl CoA from pyruvate was essentially unaffected until the arsenate concentration exceeded 0.02 m. Close agreement was observed between the amount of pyruvate utilized and the amount of acetyl phosphate formed, both in the presence and absence of arsenate. The CoA-dependent exchange of P(32)O(4) ( identical with) with acetyl phosphate proceeded at a rate approximately one-eightieth of the rate of acetylation of CoA, indicating an equilibrium value for the phosphotransacetylase reaction similar to that observed for Clostridium kluyveri. The failure of arsenate to uncouple the C. acidiurici enzyme may indicate a high degree of specificity in relation to the acetyl unit acceptor, giving preference to phosphate over arsenate.


Polymorphisms at GSTM1 and GSTP1 gene loci and risk of prostate cancer in a South Indian population.
Inter-individual differences in cancer susceptibility may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The glutathione S-transferases (GSTs), which are active in detoxification of wide variety of carcinogens, have been consistently implicated as cancer susceptibility genes in this context. We here assessed the association of GSTM1 and GSTP1 polymorphisms with susceptibility to prostate cancer in a case-control study of 75 patients and 100 age-matched controls in a South Indian population. The GSTM1 null polymorphism was detected by PCR and the GSTP1 Ile105Val polymorphism by PCR-RFLP using peripheral blood DNA. There was no significant link between the null genotype of GSTM1 and risk of prostate cancer (OR-1.79; 95% CI-0.78-4.11; P-0.18). However, the GSTP1 Ile/Val genotype was significantly associated with a decreased risk for prostate cancer (OR-0.36; 95% CI-0.18-0.73; P<0.001). Analysis of the variant GSTM1 and GSTP1 genotypes in combination did not reveal any significant difference between cases and controls, even with a stratified analysis tumor grades. Thus our study indicates that the GSTP1 Ile/Val genotype may decrease risk of prostate cancer in the South Indian population.


The Relation Between Multiple Informal Caregiving Roles and Subjective Physical and Mental Health Status Among Older Adults: Do Racial/Ethnic Differences Exist?
The present study examined whether race/ethnicity moderated the relation between type of caregiving role (none, one, or multiple care recipients) and subjective physical and mental health among older adults. The sample was drawn from the 2009 California Health Interview Survey. Racially/ethnically diverse adults aged 55 and older (n = 24,241) were categorized into 3 groups by caregiving roles: noncaregivers (n = 18,626; referent), caregivers with a single caregiving role (n = 4,023), and caregivers with multiple caregiving roles (n = 1,772). A 2-way analysis of covariance was conducted to test main and interaction effects. After adjustment for covariates, noncaregivers reported significantly worse self-rated health and lower psychological distress than caregivers with any type of role. The interaction between race/ethnicity and caregiving roles was significant only for self-rated health (p < .05). Blacks with multiple caregiving roles had poorer self-rated health than those with a single caregiving role and better self-rated health than noncaregivers, whereas other racial/ethnic groups with multiple caregiving roles had better self-rated health compared to both noncaregivers and those with a single caregiving role. Our sensitivity analysis showed that controlling caregiving-related variables present only among caregivers eliminated the differences in self-rated health between the two types of caregivers. Findings suggest that caregivers report better self-rated health than noncaregivers and that the relation of multiple caregiving roles with self-rated health differs by race/ethnicity, with blacks differing from other racial/ethnic groups. This implies that caregivers experience gain, or are selected into the role of caregiving by virtue of having good health.


Bafetinib, a dual Bcr-Abl/Lyn tyrosine kinase inhibitor for the potential treatment of leukemia.
Bafetinib (NS-187, INNO-406) is a second-generation tyrosine kinase inhibitor in development by CytRx under license from Nippon Shinyaku for treating Bcr-Abl+ leukemia's, including chronic myelogenous leukemia (CML) and Philadelphia+ acute lymphoblastic leukemia. It is a rationally developed tyrosine kinase inhibitor based on the chemical structure of imatinib, with modifications added to improve binding and potency against Bcr-Abl kinase. Besides Abl, bafetinib targets the Src family kinase Lyn, which has been associated with resistance to imatinib in CML. In preclinical studies, bafetinib was 25- to 55-fold more potent than imatinib in vitro and ≥ 10-fold more potent in vivo. Bafetinib inhibits 12 of the 13 most frequent imatinib-resistant Bcr-Abl point mutations, but not a Thr315Ile mutation. A small fraction of bafetinib crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. Data from a phase I clinical trial conducted in patients with imatinib-resistant or -intolerant CML have confirmed that bafetinib has clinical activity in this setting, inducing a major cytogenetic response in 19% of those patients in chronic phase. Currently, bafetinib is being developed in two phase II clinical trials for patients with B-cell chronic lymphocytic leukemia and prostate cancer, and a trial is in progress for patients with brain tumors.


Structural and magnetic study of order-disorder behavior in the double perovskites Ba2Nd1-xMnxMoO6.
The synthesis and structural and magnetic characterization of the site-ordered double perovskites, Ba2Nd1-xMnxMoO6, 0 < x ≤ 1, are reported in order to show the effect of doping Jahn-Teller active, S = 1/2, Mo(5+) into the structure of Ba2MnMoO6, which exhibits anomalous long-range antiferromagnetic order. Rietveld refinements against room temperature neutron powder diffraction data indicate that the tetragonal distortion present in the Ba2NdMoO6 end member persists to x ≤ 0.3. This is predominantly manifested as a tilting of the MO6 octahedra, and there is no evidence of any structural phase transitions on cooling to 1.5 K. For x > 0.3, no deviation from the ideal cubic Fm3̅m symmetry is observed. Furthermore, dc-susceptibility measurements confirm that Mn(2+) is being doped onto the Nd(3+) site, and the associated oxidation of Mo(5+) to Mo(6+). For all compositions, the Curie-Weiss paramagnetic behavior above 150 K indicates negative Weiss constants that range from -24(2) and -85(2) K. This net antiferromagnetic interaction is weakest when x ≈ 0.5, where the disorder in cation site occupancy and competition with ferromagnetic interactions is the greatest. Despite these strong antiferromagnetic interactions, there is no evidence in the dc-susceptibility of a bulk cancellation of spins for x > 0.05. Low-temperature neutron diffraction measurements indicate that there is no long-range magnetic order for 0.1 ≤ x < 0.9. Ba2Nd0.10Mn0.90MoO6 exhibits additional Bragg scattering at 2 K, indicative of long-range antiferromagnetic ordering of the Mn(2+) cations, with a propagation vector k = (1/2, 1/2, 1/2). The scattering intensities can be modeled using a noncollinear magnetic structure with the Mn(2+) moments orientated antiferromagnetically along the four different ⟨111⟩ directions.


Surviving within the amoebal exocyst: the Mycobacterium avium complex paradigm.
Most of environmental mycobacteria have been previously demonstrated to resist free-living amoeba with subsequent increased virulence and resistance to antibiotics and biocides. The Mycobacterium avium complex (MAC) comprises of environmental organisms that inhabit a wide variety of ecological niches and exhibit a significant degree of genetic variability. We herein studied the intra-ameobal location of all members of the MAC as model organisms for environmental mycobacteria. Type strains for M. avium, Mycobacterium intracellulare, Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense, Mycobacterium marseillense, Mycobacterium timonense and Mycobacterium bouchedurhonense were co-cultivated with the free-living amoeba Acanthamoeba polyphaga strain Linc-AP1. Microscopic analyses demonstrated the engulfment and replication of mycobacteria into vacuoles of A. polyphaga trophozoites. Mycobacteria were further entrapped within amoebal cysts, and survived encystment as demonstrated by subculturing. Electron microscopy observations show that, three days after entrapment into A. polyphaga cysts, all MAC members typically resided within the exocyst. Combined with published data, these observations indicate that mycobacteria are unique among amoeba-resistant bacteria, in residing within the exocyst.


Regulatory roles of introns in fungicide sensitivity of Fusarium graminearum.
Although the roles of introns have been much debated in eukaryotic organisms, none of them have been functionally characterized in Fusarium graminearum. In this study, we characterized the roles of introns in regulation of fungicide-sensitivity of F. graminearum. β2 tub, cyp51A and myosin-5 are important target genes of benzimidazoles, triazoles and cyanoacrylates respectively. To explore the sensitivity regulation functions of introns in target genes, several detailed deletion studies were completed on the intronic regions of β2 tub, cyp51A and myosin-5. Phenotypic analyses showed that deletion of the fourth intron from β2 tub gene (designated β2 Δi4), the sole intron from cyp51A gene (cyp51A-Δi) and the second intron from myosin-5 gene (myo5-Δi2) exhibited an increased sensitivity to corresponding fungicides. In contrast, deletion of the first or second intron from β2 tub gene exhibited a decreased sensitivity to carbendazim. qRT-PCR showed that the mRNA transcript levels of target genes were significantly downregulated in β2 Δi4, cyp51A-Δi and myo5-Δi2 respectively. Meanwhile, Western blot assays revealed that the protein expression levels of β2 tub was also dramatically reduced in β2 Δi4, but accumulated in β2 Δi1 and β2 Δi2. Overall, our results indicate that introns in target genes significantly regulate the fungicide-sensitivity by influencing expression of the corresponding resident genes in F. graminearum.


Specificity of the actinomycin-D-sensitive function of some RNA plant viruses.
The actinomycin-D(AMD)-sensitive step of replication of three plant viruses - cowpea chlorotic mottle virus (CCMV), cowpea mosaic virus, and the cowpea strain of tobacco mosaic virus - in cowpea was specific for each virus. Different combinations of the viruses were examined in which leaves were inoculated with one virus and incubated for 48 h until multiplication was almost resistant to AMD. At that time, the same leaves were inoculated with a different virus and the ability of AMD to inhibit multiplication of the second virus was determined at intervals afterwards. In all combinations tested, the first virus had no effect on the sensitivity of the second virus to AMD. Also, resistance to AMD, which appeared to spread from cell to cell in advance of the virus in mechanically inoculated leaves, did not spread appreciably faster than CCMV into systemically infected upper leaves.


Estimates of available iron in diets of individuals 1 year old and older in the Nationwide Food Consumption Survey.
Levels of total iron and available iron were estimated in the diets of individuals 1 year and older. The source of data was 1-day dietary recall records from the U.S. Department of Agriculture's 1977-78 Nationwide Food Consumption Survey. Total iron intakes of 1- to 2- and 3- to 5-year-old children were 51% and 77% of their respective RDAs. Total iron intakes of 12- to 50-year-old girls and women averaged only 55% to 61% of their RDA. Total iron intakes of other groups came close to or exceeded their respective RDAs. The proportion of total iron calculated to be available ranged from 6.5% to 8.7%, which is less than the 10% assumption of availability used as a basis for setting the iron RDA. When compared with the RDAs, total iron presented a more favorable picture of dietary iron intake than available iron. In relation to the RDAs, proportions of available iron were consistently lower than proportions of total iron. Available iron was lower than total iron in relation to recommended allowances because less than 10% of total dietary iron was available.


Relationship between sugar structure and competition for the sugar transport system in Bakers' yeast.
Twenty-five sugars have been compared as inhibitors of l-sorbose or d-xylose transport by the constitutive, monosaccharide transport system in bakers' yeast. d-Glucose showed the highest activity (i.e., apparent K(i) = 5 mm). Since all sugars except 2-deoxyglucose showed a decrease in activity relative to glucose (i.e., apparent K(i) = 25 - >2,000 mm), an attempt was made to relate the activity of each sugar with the way its structure differs from that of d-glucose. Assuming that the inhibition was the result of sugar-carrier complex formation, the analysis showed that the transport system has a rather broad specificity for pyranoses. Single changes at each of the five carbons of d-glucose (except for the 2-deoxy derivative) result in variable decreases in activity depending upon the carbon number and the alteration. The largest decrease in activity effected by a single change is the methylation or glucosylation of the anomeric hydroxyl. The combination of two or more changes leads to a decrease which is greater than the decrease in activity resulting from the individual changes occurring alone.


Sirolimus-eluting stent implantation for bare-metal in-stent restenosis: is there any evidence for a late catch-up phenomenon?
In-stent restenosis occurs not infrequently after intracoronary implantation of bare-metal stents. Many techniques have been proposed for the treatment of in-stent restenosis, but drug-eluting stents seem to provide the best early and mid-term results. We aimed to appraise whether the effectiveness of drug-eluting stents for in-stent restenosis is maintained even in the long term. Participants in this prospective multicenter study were patients with in-stent restenosis treated with sirolimus-eluting stents. The primary endpoint was freedom from major adverse cardiovascular events (i.e. death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis) in the long term (> or =24 months), with 6-month angiography planned for all patients. A total of 271 consecutive patients were enrolled (332 sirolimus-eluting stents). Procedural success was obtained in all patients, with no case of in-hospital death, acute/subacute stent thrombosis, stroke, or urgent coronary bypass. Survival free from major cardiovascular events decreased progressively from 98.8% at 1 month, to 95.7, 83.7, 75.4, and 65.8% at 6, 12, 24, and 30 months, respectively. A similar attrition in freedom from repeat target vessel was found from 97.6% at 6 months to 76.7% at 30 months. A total of four possible and one definite stent thromboses (2.6%) were noted, all occurring several months after clopidogrel discontinuation and in patients on life-long aspirin. The present study supports the mid-term safety and effectiveness of sirolimus-eluting stents for the treatment of in-stent restenosis in comparison with the other available treatments. Whether the late catch-up phenomenon observed in repeat target revascularization and stent thrombosis is an incidental finding deserves further rigorous scrutiny.


Recent Advances in Ionic Liquids in Biomedicine.
The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task-specific solvents.


Exploring cognitive skill development in midwifery education.
Changes in maternity services and the role of the midwife mean that the midwife must provide flexible, evidence-based, woman-centred care. As the lead professional, the midwife must use a high level of professional judgement, clinical reasoning and decision-making to enable choice while ensuring the safety and wellbeing of mother and infant. Delayed development of these cognitive skills is suggested by the continuing theory-practice gap, suboptimal practice and students requiring to conform to non-evidence-based practice. The purpose of this research was to explore midwifery students' understanding and experience of the development of cognitive skills. The research employed analysis of undergraduate midwifery programme documentation and a focus group discussion with student midwives from second and third year of the programme. Document analysis and thematic analysis of the interview data indicated a lack of emphasis on cognitive skill development and a sense that these skills improve naturally through exposure to clinical practice. The findings suggest a need to change our approach to learning in clinical practice and to conduct further research to improve understanding of mechanisms to support the development of cognitive skills.


Enforced expression of E47 has differential effects on Lmo2-induced T-cell leukemias.
LIM domain only-2 (LMO2) overexpression in T cells induces leukemia but the molecular mechanism remains to be elucidated. In hematopoietic stem and progenitor cells, Lmo2 is part of a protein complex comprised of class II basic helix loop helix proteins, Tal1and Lyl1. The latter transcription factors heterodimerize with E2A proteins like E47 and Heb to bind E boxes. LMO2 and TAL1 or LYL1 cooperate to induce T-ALL in mouse models, and are concordantly expressed in human T-ALL. Furthermore, LMO2 cooperates with the loss of E2A suggesting that LMO2 functions by creating a deficiency of E2A. In this study, we tested this hypothesis in Lmo2-induced T-ALL cell lines. We transduced these lines with an E47/estrogen receptor fusion construct that could be forced to homodimerize with 4-hydroxytamoxifen. We discovered that forced homodimerization induced growth arrest in 2 of the 4 lines tested. The lines sensitive to E47 homodimerization accumulated in G1 and had reduced S phase entry. We analyzed the transcriptome of a resistant and a sensitive line to discern the E47 targets responsible for the cellular effects. Our results suggest that E47 has diverse effects in T-ALL but that functional deficiency of E47 is not a universal feature of Lmo2-induced T-ALL.


Structure and in vitro transcription of a glycine tRNA gene from Bombyx mori.
We report the sequences of a Bombyx mori tRNA1Gly gene, its flanking regions, and its in vitro transcription products. The 5' flanking DNA contains the sequences TATAC, TATTTT and TTC located 30, 18 and 4 nucleotides, respectively, in front of the transcription initiation site. These resemble, in both position and composition, sequences preceding other RNA polymerase III genes of B. mori. A deletion mutant retaining these conserved sequences and an additional 8 bp of flanking DNA is transcribed better than the wild-type gene in cell-free extracts from Xenopus laevis and B. mori. A mutant lacking the conserved sequences is expressed in the frog extract, but is inactive in the homologous system.


[Liver abscesses with portal and mesenteric vein thrombosis in combination with late onset of appendicitis].
Pyogenic liver abscesses are caused by appendicitis in less than 10%. Also the ascending septic inflammation of portal vein (pylephlebitis) could be a serious complication of intra-abdominal infection. Although pylephlebitis is not frequent today, its' mortality and morbidity rates remain high. We describe a case of young man with fever, abdominal pain, and multiple hepatic abscesses. After the symptomatic relief due to antibiotic therapy the pain returned as a result of the development of portal and mesenteric vein thrombosis. The cause of either hepatic abscesses or thrombosis was not clear at the time of dismissal. 2 months later the patient underwent acute abdominal revision with appendectomy for acute phlegmonous and gangrenous appendicitis. Since that time he has been without any clinical symptoms.


Topical analgesia for the cutting of split-skin grafts: a multicenter comparison of two doses of a lidocaine/prilocaine cream.
The topical analgesic effect of two doses of a local anesthetic cream (EMLA, Astra) in the harvesting of split-skin grafts was compared in a double-blind multicenter trial. A standardized area of 200 cm2 at the donor site of 78 patients was randomly treated with 30 or 60 gm of cream 2 to 5 hours before the operation. There was no difference in pain between the groups (p = 0.53). In each group, 92 percent of the patients rated the pain as either none or slight, and 8 percent rated it as either moderate or severe. In conclusion, with the application times of 2 to 5 hours used in this trial, a dose of 15 gm EMLA cream per 100 cm2 is sufficient to provide analgesia for the cutting of split-skin grafts.


[Early septicemia episodes in 143 bone marrow grafts].
Twenty-one early bacteremias have occurred before engraftment in 143 allogeneic bone marrow transplantation recipients. In the majority of cases (13/21) Gram positive cocci were isolated with a predominance of coagulase-negative staphylococci (62%). The analysis of the infection prevention program showed that: 1) the adjunction of vancomycin to a total gut decontamination did not decrease significantly the incidence of bacteremia caused by Gram positive cocci. 2) The isolation in laminar air flow room seems to decrease the severity of infections but does not influence their frequency.


Randomized controlled trial of neurofeedback on chemotherapy-induced peripheral neuropathy: A pilot study.
Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors. This was a randomized controlled trial with survivors assigned to an NFB group or a wait-list control (WLC) group. The NFB group underwent 20 sessions of NFB, in which visual and auditory rewards were given for voluntary changes in EEGs. The Brief Pain Inventory (BPI) worst-pain item was the primary outcome. The BPI, the Pain Quality Assessment Scale, and EEGs were collected before NFB and again after treatment. Outcomes were assessed with general linear modeling. Cancer survivors with CIPN (average duration of symptoms, 25.3 mo), who were mostly female and had a mean age of 62.5 years, were recruited between April 2011 and September 2014. One hundred percent of the participants starting the NFB program completed it (30 in the NFB group and 32 in the WLC group). The NFB group demonstrated greater improvement than the controls on the BPI worst-pain item (mean change score, -2.43 [95% confidence interval, -3.58 to -1.28] vs 0.09 [95% confidence interval, -0.72 to -0.90]; P =·.001; effect size, 0.83). NFB appears to be effective at reducing CIPN symptoms. There was evidence of neurological changes in the cortical location and in the bandwidth targeted by the intervention, and changes in EEG activity were predictive of symptom reduction. Cancer 2017;123:1989-1997. © 2017 American Cancer Society.


Hereditary Polyposis Syndromes: Opportunities for Early Detection in Individuals and Families
People with multiple polyps may have a germline mutation that places them at higher risk for developing colorectal, gastrointestinal, and other cancers. Genetic testing can often identify the specific polyposis syndrome and provide insight into appropriate recommendations for cancer prevention and early detection. Individuals with hereditary polyposis syndromes often begin developing polyps in their teenage years and require aggressive gastrointestinal surveillance to remove polyps. For some, the polyp burden will be too high to manage endoscopically and will require risk-reducing colectomies. Identification of individuals with hereditary polyposis syndromes may help to reduce morbidity and mortality. .


Construction and effect evaluation of different sciatic nerve injury models in rats.
The most commonly used experimental model for preclinical studies on peripheral nerve regeneration is the sciatic nerve injury model. However, no experimental study has been conducted to evaluate acute injury modes at the same time. We conducted sciatic nerve transverse injury, clamp injury, keep epineurium and axon cutting injury, and chemical damage injury in rats to evaluate the degree of damage of the four different injury modes and the degree of self-repair after injury. The sciatic nerve transverse injury model, clamp injury model, keep epineurium injury model, and chemical damage injury model were constructed. Then, the sciatic nerve function was assessed using clinical evaluation methods and electrophysiological examinations, as well as immunofluorescence and axonal counting assessments of the reconstructed nerve pathways. The evaluations showed that the transverse group had the lowest muscle action potential, sciatic functional index, nociceptive threshold, mechanical threshold, rate of wet gastrocnemius muscle weight, area of muscle fiber, and numbers of myelinated nerve fibers. The chemical group had the highest, while the clamp group and the keep epineurium group had medium. Transverse injury models have the most stable effect among all damage models; chemical injury models self-recover quickly and damage incompletely with poor stability of effect; and clamp injury models and keep epineurium injury models have no significant differences in many ways with medium stability.


The molecular genetics of complex inherited diseases.
The majority of inherited diseases are due to unknown biochemical defects, or are either polygenetic or multifactorial. Due to advances in molecular genetics, it is now possible to study these conditions, either by reverse genetics (using cloning techniques to move from linkage to gene, and then determining the protein involved) or by dissecting a complex disease into a set of monogenic paradigms.


The PharmNet Harm Reduction Intervention for Community Pharmacies: Protocol for a Pilot Randomized Controlled Trial.
The overdose epidemic in the United States has continued to worsen despite substantial efforts to mitigate its harms. The opioid antagonist naloxone has been identified as a key means of reducing the prevalence of fatal overdoses. An important evidence-based approach to optimizing naloxone's impact is to seed it throughout the community, because bystanders are often able to reverse overdoses more quickly than first responders and sometimes are the only possible means of overdose reversal. As part of a multipronged approach to distributing naloxone nationwide, community pharmacies have been identified as ideal venues for naloxone dispensing, especially under standing orders. However, dispensing rates remain surprisingly low, and there is a need to understand how best to engage community pharmacies in naloxone-based harm reduction services. The objective of this trial is to determine whether a tailored, pragmatic pharmacy intervention (PharmNet) results in greater naloxone dispensing relative to baseline (the prior 3 months) compared to a control condition. This pilot trial is intended to determine whether it is appropriate to invest the substantial resources that would be required to conduct a full-scale, randomized controlled study of PharmNet. We will conduct a 3-month randomized controlled pilot trial consisting of 2 parallel groups with a 4:3 allocation ratio. A group of 7 independent pharmacies from rural areas in Indiana will be randomly assigned to either the PharmNet intervention arm (n=4) or the control arm (n=3). The primary outcome will be overall naloxone dispensing (both at cost and free), and secondary outcomes will include the distribution of referral cards and multiple variables at the level of individual staff members. Dispensing data will be collected for the 3 months prior to the intervention and the 3 months of the intervention, and all other data will be collected using a pretest-posttest design. The primary analysis will be a generalized linear mixed model with a Poisson distribution with fixed effects for group, time, and their interaction and a random effect for pharmacy ID to account for repeated measures within pharmacies. This study was approved by the Indiana University institutional review board in 2 phases (August 2, 2021, and April 26, 2022) and was funded by the Indiana University Grand Challenge: Responding to the Addictions Crisis. If this study produces evidence that the PharmNet intervention results in increased naloxone dispensing relative to control pharmacies, it will be both appropriate and important to study it in a large, full-scale randomized controlled trial. PRR1-10.2196/42373.


Midterm health and personnel outcomes of recent combat amputees.
Warfighters who sustained combat amputations in Operation Enduring Freedom or Operation Iraqi Freedom (OEF/OIF) have unique challenges during rehabilitation. This study followed their outcomes. Subjects were 382 U.S. warfighters with major limb amputations after combat injury in OEF/OIF between 2001 and 2005. Outcome measures were diagnoses, treatment codes, and personnel events captured by health and personnel databases during 24 months postinjury. Most patients had multiple complications generally within 30 days postinjury (e.g., infections, anemia), with important exceptions (e.g., heterotopic ossification). Lower limb amputees had 50% more complications than upper limb amputees. Two-thirds of patients had a mental health disorder (e.g., adjustment, post-traumatic stress disorder), with rates of major disorder categories between 18% and 25%. Over 80% of patients used physical and occupational therapy, prosthetic/orthotic services, and psychiatric care. Combat amputees had a complex set of outcomes supporting the continued need for military amputee care programs.


[Traumatology in the elderly. Problems from the anesthesiologic point of view].
In order to prevent cardiopulmonary complications, persons injured in an accident should be operated immediately and remobilized afterwards as soon as possible, especially if they are old. Preexistent diseases that could possibly be improved should be treated adequately before operation. Concerning the kind of anaesthesia, for operations of the lower extremities we usually prefer general anaesthesia. Operations of the upper extremities are carried out whenever possible under a subaxillary block. The postoperative treatment on the ICU or a regular ward includes physical therapy and emphasizes early mobilisation of the patient.


Conservation of S20 as an Ineffective and Disposable IFNγ-Inducing Determinant of Plasmodium Sporozoites Indicates Diversion of Cellular Immunity.
Despite many decades of research to develop a malaria vaccine, only one vaccine candidate has been explored in pivotal phase III clinical trials. This candidate subunit vaccine consists of a portion of a single Plasmodium antigen, circumsporozoite protein (CSP). This antigen was initially identified in the murine malaria model and shown to contain an immunodominant and protective CD8+ T cell epitope specific to the H-2K d (BALB/c)-restricted genetic background. A high-content screen for CD8+ epitopes in the H2K b /D b (C57BL/6)-restricted genetic background, identified two distinct dominant epitopes. In this study, we present a characterization of one corresponding antigen, the Plasmodium sporozoite-specific protein S20. Plasmodium berghei S20 knockout sporozoites and liver stages developed normally in vitro and in vivo. This potent infectivity of s20(-) sporozoites permitted comparative analysis of knockout and wild-type parasites in cell-based vaccination. Protective immunity of irradiation-arrested s20(-) sporozoites in single, double and triple immunizations was similar to irradiated unaltered sporozoites in homologous challenge experiments. These findings demonstrate the presence of an immunogenic Plasmodium pre-erythrocytic determinant, which is not essential for eliciting protection. Although S20 is not needed for colonization of the mammalian host and for initiation of a blood infection, it is conserved amongst Plasmodium species. Malarial parasites express conserved, immunogenic proteins that are not required to establish infection but might play potential roles in diverting cellular immune responses.


Structure and expression of cytosolic cyclophilin/peptidyl-prolyl cis-trans isomerase of higher plants and production of active tomato cyclophilin in Escherichia coli.
cDNA clones encoding proteins of approximately 18 kDa in which 83% of the amino acids are conserved relative to the published sequences of mammalian cyclophilin/rotamase (CyP) have been isolated from tomato, maize, and Brassica napus. In correspondence with the mammalian genes, but in contrast with the Neurospora gene and one yeast CyP gene, the plant CyP genes encode only mature proteins lacking transit peptides. RNA blot analyses demonstrate that CyP genes are expressed in all plant organs tested. Southern blots of genomic DNA indicate that there are small families (two to eight members) of CyP-related genes in maize and B. napus. A vector was constructed for expression of the tomato cDNA in E. coli. SDS/polyacrylamide gels show that extracts of appropriately induced cells harboring this vector contain nearly 40% of the protein as a single approximately 18-kDa band. While the majority of this protein is sequestered in insoluble inclusion bodies, the soluble extracts have higher levels of peptidyl-prolyl cis-trans isomerase (rotamase) activity than extracts of wild-type cells. This additional activity is sensitive to inhibition by the cyclic undecapeptide cyclosporin A.


Synthesis of diastereoisomeric peptides incorporating cycloglutamic acids. Substrate specificity of vitamin K-dependent carboxylation.
Tripeptides Boc-X-Glu-Val where X is alpha-methyl glutamic acid or various cyclic analogues of glutamic acid, such as 1-amino-1,3-dicarboxycyclohexane (cis or trans-CHGA) or -cyclopentane (cis or trans-CPGA) have been synthesized. Methods for the selective protection, activation, and coupling of such unnatural amino acids are described. The peptides, which are potential competitive inhibitors of the vitamin K-dependent carboxylation, have been preliminarily tested with the rat liver microsomal carboxylase and found to be effective substrates of the carboxylation reaction.


Medical therapy for benign prostatic hyperplasia: new terminology, new concepts, better choices.
This article discusses 3 areas of medical therapy for benign prostatic hyperplasia (BPH) that are undergoing extensive research and evaluation: 1) the use of muscarinic receptor antagonists to treat lower urinary tract symptoms (LUTS) in men with BPH; 2) the definition of an "enlarged prostate"; and 3) sexual function and LUTS. Fears of worsening obstructive symptoms or causing acute urinary retention often keep practitioners from prescribing muscarinic receptor antagonists to men who might have concomitant bladder outlet obstruction; a multicenter, multinational, double-blind study showed that tolterodine is safe for men with low postvoid residual volumes. Most urologists accept that a prostate volume of more than 40 mL is consistent with an enlarged prostate; there is more debate regarding prostate volumes of 30 to 40 mL. Recently presented data suggest that combination medical therapy might be effective for men having prostates with volumes of more than 25 mL. The association between voiding and sexual function has been increasingly recognized and investigated, and there seem to be common pathophysiologic mechanisms governing both conditions. Targeted treatment algorithms addressing both conditions seem warranted.


Has Current French Training for Military Orthopedic Surgeons Deployed in External Operations Been Appropriately Adapted?
The current evolution of surgical practices is increasingly trending toward hyper-specialization. For military surgeons, their practice in France does not differ from their civilian counterparts. In contrast, in external operations, they have to deal with specific war injuries in austere conditions. They are also required to take care of local populations. Therefore, specific training is necessary, and the French Military Health Service Academy (Ecole du Val-de-Grâce) Paris has set up a specific training called Advanced Course for Deployment Surgery (ACDS) in 2007. The aim of this study is to assess the relevance of this teaching regarding pathologies encountered during current conflicts. The activity of deploying orthopedic surgeons during the three recent major external operations (Afghanistan, Mali, and Central African Republic) has been retrospectively recorded in terms of global volume, types of trauma, status of patients who had been operated on, and indications. These data have been compared with teaching during the ACDS. Our study found a high variability in terms of operating volume, types of trauma, patients' statuses, and types of operations performed depending on the operation theaters. The volume of surgical activity carried out within Role 3 is much more important than that in Role 2 with more than half of the surgeries performed as scheduled surgery to the benefit of the local population. Within advanced Role 2 surgical structures deployed in Mali and Central Africa, more than 70% of the activity was performed as emergencies. Surgical indications were varied, ranging from emergency surgery to limb reconstructive surgery. A lot of non-orthopedic procedures such as vascular repairs and decompressive craniotomies were also performed. All of the encountered pathologies were taught during ACDS. The large variety and technical nature of the performed operations requires the training of highly qualified military orthopedic surgeons with both experience in war surgery and management of after-effects and complications. Orthopedists are also required to carry out procedures dealing with neurosurgery, general, and/or vascular surgery on missions. These data highlight the complexity of military surgeons' training along with the hyper-specialization of the civilian medical world. For more than 10 yr, French military surgeons have benefited from a training program called ACDS to meet these objectives. This initial training seems to be appropriated adapted in view of the managed pathologies.


Systemic Inflammatory Response After Open, Laparoscopic and Robotic Surgery in Endometrial Cancer Patients.
To study inflammatory response and nutritional biomarkers in operated endometrial cancer (EC) patients. A total 109 consecutive EC patients undergoing open laparotomy (LT), laparoscopic (LS) or robot-assisted surgery (RS) were studied. Twenty four patients served as controls. Pre- and postoperative levels of inflammatory and nutritional biomarkers were analyzed prospectively. The estimated blood loss was significantly lower in RS compared to all other groups. C-reactive protein (CRP) and interleukin-6 (IL-6) correlated with each other and exhibited positive correlation with age, body-mass index (BMI), leukocyte count, platelet count, kynurenine, kynurenine/tryptophan ratio and urinary neopterin and a negative correlation with vitamin D and retinol. Hemoglobin, retinol, alpha-tocopherol, vitamin D and citrulline concentrations decreased and inflammatory biomarkers increased after surgery to a different extent in LT, LS, RS and control groups. The present data demonstrate a differential response to surgical trauma in patients with endometrial carcinoma.


Dual blockade of BRD4 and ATR/WEE1 pathways exploits ARID1A loss in clear cell ovarian cancer.
ARID1A, an epigenetic tumor suppressor, is the most common gene mutation in clear-cell ovarian cancers (CCOCs). CCOCs are often resistant to standard chemotherapy and lack effective therapies. We hypothesized that ARID1A loss would increase CCOC cell dependency on chromatin remodeling and DNA repair pathways for survival. We demonstrate that combining BRD4 inhibitor (BRD4i) with DNA damage response inhibitors (ATR or WEE1 inhibitors; e.g. BRD4i-ATRi) was synergistic at low doses leading to decreased survival, and colony formation in CCOC in an ARID1A dependent manner. BRD4i-ATRi caused significant tumor regression and increased overall survival in ARID1AMUT but not ARID1AWT patient-derived xenografts. Combination BRD4i-ATRi significantly increased γH2AX, and decreased RAD51 foci and BRCA1 expression, suggesting decreased ability to repair DNA double-strand-breaks (DSBs) by homologous-recombination in ARID1AMUT cells, and these effects were greater than monotherapies. These studies demonstrate BRD4i-ATRi is an effective treatment strategy that capitalizes on synthetic lethality with ARID1A loss in CCOC.


S-layer and cytoplasmic membrane - exceptions from the typical archaeal cell wall with a focus on double membranes.
The common idea of typical cell wall architecture in archaea consists of a pseudo-crystalline proteinaceous surface layer (S-layer), situated upon the cytoplasmic membrane. This is true for the majority of described archaea, hitherto. Within the crenarchaea, the S-layer often represents the only cell wall component, but there are various exceptions from this wall architecture. Beside (glycosylated) S-layers in (hyper)thermophilic cren- and euryarchaea as well as halophilic archaea, one can find a great variety of other cell wall structures like proteoglycan-like S-layers (Halobacteria), glutaminylglycan (Natronococci), methanochondroitin (Methanosarcina) or double layered cell walls with pseudomurein (Methanothermus and Methanopyrus). The presence of an outermost cellular membrane in the crenarchaeal species Ignicoccus hospitalis already gave indications for an outer membrane similar to Gram-negative bacteria. Although there is just limited data concerning their biochemistry and ultrastructure, recent studies on the euryarchaeal methanogen Methanomassiliicoccus luminyensis, cells of the ARMAN group, and the SM1 euryarchaeon delivered further examples for this exceptional cell envelope type consisting of two membranes.


Braid topologies for quantum computation.
In topological quantum computation, quantum information is stored in states which are intrinsically protected from decoherence, and quantum gates are carried out by dragging particlelike excitations (quasiparticles) around one another in two space dimensions. The resulting quasiparticle trajectories define world lines in three-dimensional space-time, and the corresponding quantum gates depend only on the topology of the braids formed by these world lines. We show how to find braids that yield a universal set of quantum gates for qubits encoded using a specific kind of quasiparticle which is particularly promising for experimental realization.


ACTION OF NEW 3-HYDROXYPYRIDINE DERIVATIVES WITH ANTI-NAUPATHIA PROPERTIES ON CENTRAL NEURONS.
Experiments with cats showed that microinjections into the lung of new 3-hydroxypyridine derivatives SK-119 and IBKhF-27 had a direct action on 50 and 84 % of medial vestibular nucleus (MVN) neurons respectively. The inhibitory response to the compounds was observed 6 and 25 times more frequently than exciting; inhibition by IBKhF-27 was observed 1.9 times more frequently than by SK-119. Also, microinjections of SK-1 19 and IBKhF-27 acted directly on 44 % and 81 % of cat's Purkinje cells, respectively. In case of Purkinje cells, the inhibitory reaction was seen 5.5 and 25 times oftener than exciting, respectively, and inhibition by IBKhF-27 occurred 2.1 times more frequently than by SK-119. Investigations of rat's cerebellum sections evidenced that 5 mM of IBKhF-27 inhibited population responses of Purkinje cells 95 1 3 %. In the presence of specific noncompetitive NMDA-receptor antagonist (MK-801, 100 pM) the depressive effect was annulled almost fully by 96 * 2 %. It follows that IBKhF-27 nearly entirely inhibits synaptic transmission from cerebellar parallel fibers to Purkinje cells, while MK-801 has a similarly strong anti-depression effect that testifies the involvement of the NMDA-receptor complex predominantly.


Role of poly(ADP-ribose) polymerase activation in the pathogenesis of periodontitis in diabetes.
The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP-ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor. Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5-isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP-ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro-CT analyses. Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine-positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor. These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.


Homogeneous Assays of Second Messenger Signaling and Hormone Secretion Using Thermofluorimetric Methods That Minimize Calibration Burden.
Homogeneous assays are characterized by rapidity, low cost, and simple workflows. However, relatively few specialized homogeneous platforms have garnered significant use in biological studies. Inconsistencies in matrix interferences, limited multiplexability, and the requirement for specialized instrumentation are among the various reasons for delayed acceptance. Recently, we have shown that DNA-driven protein assays using thermofluorimetric analysis (TFA) can limit matrix interference and promote multiplexing, all while requiring only a standard qPCR instrument for readout. Here, we show that homogeneous, one step (mix-and-read) TFA methods can be extended to the analysis of both a small molecule second messenger, cyclic adenosine monophosphate (cAMP), and a downstream cell-secreted hormone, insulin. Differential thermal analysis of DNA melting in these assays allowed analytical discrimination of background and signal without physical separation. The direct-readout, differential nature of TFA also promoted assay consistency and minimized calibration burden; analyte response curves were shown to be highly repeatable for up to 7 months. TFA protocols were validated by homogeneous quantification of both cAMP and insulin from single pancreatic islets undergoing a variety of treatments (glucose, KCl, glucose-responsive insulinotropic peptide (GIP), forskolin) that act upon glucose transporters, potassium and calcium channels, and G-protein-coupled receptors to modulate exocytosis. The results of this study suggest that TFA should be applicable to homogeneous quantification of a variety of small molecule messengers and protein analytes with standard instrumentation, thereby simplifying workflows in studies of cell-signaling cascades.


Pyridine-2,4-dicarboxylate: a versatile building block for the preparation of functional coordination polymers.
The hydrothermal reaction of the pyridine-2,4-dicarboxylate (2,4-pdc) dianion with various 3d metal(II) cations resulted in the formation of a series of one-, two- and three-dimensional coordination polymers with varied network topologies. 2,4-pdc reacted directly with MnCI2 or FeCl2 in water at 200 degrees C under mild basic conditions to give a dense three-dimensional polymer, [M(2,4-pdc)] (M = Mn, 1a; M = Fe, 1b), which supports a highly-connected three-dimensional magnetic exchange lattice. Both 1a and 1b undergo antiferromagnetic ordering and the latter Fe(II)-containing material exhibited spin-canting behavior below 6.5 K. Reaction of 2,4-pdc with CoCl2 under identical conditions gave an unusual zigzag chain polymer, [Co4(2,4-pdc)4(OH2)10] (2), that has large amounts of coordinated H2O. The magnetism of 2 based on isolated Co(II) dimers was modeled using a modified van Vleck approach. Adjustment of the reaction pH resulted in the formation of additional Co(II)-containing materials with strongly contrasting structures: at lower pH in the presence of oxalic acid, the same reaction components gave a protonated molecular species, [Co(2,4-pdcH)2(OH2)2]. 2H2O (3); at higher pH in the presence of excess hydroxide, a highly porous, three-dimensional material was obtained, [Co3(micro3-OH)2(2,4-pdc)2] x 9H2O (4a). 4a contains cobalt hydroxide chains, whose magnetic behavior has been studied in detail by neutron diffraction. A Ni(II)-containing analogue was also prepared using NiCI2 (4b), which shows weak antiferromagnetic coupling. Attempts to obtain a Zn(II)-based analogue of the porous material 4 gave instead a unique coordination material, [Zn(micro2-OH)2(2,4-pdc)] (5), which contains uncommon zinc hydroxide bridging modes.


Tetrabutylphosphonium Bromide Reduces Size and Polydispersity Index of Tat2:siRNA Nano-Complexes for Triticale RNAi.
Cell-penetrating peptides (CPPs) are short 8-30 amino-acid oligopeptides that act as effective transducers of macromolecular cargo, particularly nucleic acids. They have been implemented in delivering dsDNA, ssDNA, and dsRNA into animal and plant cells. CPPs and nucleic acids form nano-complexes that are often 100-300 nm in size but still effectively transit the cell membrane of animal cells, but are less effective with plant cells due to the plant cell wall. To overcome this obstacle, nano-complexes of the CPP Tat2 and various lengths of nucleic acid (21-mer siRNA duplex (dsRNA) to ~5.5 kb circular plasmid) were evaluated for size using dynamic light scattering (DLS), under conditions of increasing ionic strength (Ic) and addition of phase transfer catalyst salts (tetrabutylammonium bromide-TBAB and tetrabutylphosphonium bromide-TBPB) and sugars (maltose-mannitol solution). It was found that the combination of 21-mer siRNA:Tat2 complexes with TBPB produced small 10-20 nm diameter nano-complexes with a polydispersity index (PDI) of ~0.1. Furthermore, it was found that for each length of nucleic acid that a linear mathematical relationship existed between the theoretical volume of the nano-complex and the nucleic acid length. Next, nano-complex formulation was tested for its ability to carry small interfering RNA molecules into plant cells and to trigger silencing of phytoene desaturase (PDS) in Triticale leaves. RT-qPCR showed 75% suppression of PDS, demonstrating that TBPB acts as an adjuvant in effecting the entry and efficacy of siRNA in young Triticale plants.


Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project.
Differences between blacks and whites have been reported in the incidence of several forms of cardiovascular disease, including hypertension and stroke. We examined racial differences in the incidence of cardiac arrest in a large urban population and in subsequent survival. We collected data on all nontraumatic, out-of-hospital cardiac arrests in Chicago from January 1, 1987, through December 31, 1988, and compared the incidence and survival rates for blacks and whites. We examined the association between survival and race and seven other known risk factors by logistic-regression analysis. We computed incidence rates by coupling our data with U.S. Census population data. Our study population comprised 6451 patients: 3207 whites, 2910 blacks, and 334 persons of other races. The incidence of cardiac arrest was significantly higher for blacks than for whites in every age group. The survival rate after cardiac arrest was 2.6 percent in whites, as compared with 0.8 percent in blacks (P < 0.001). Blacks were significantly less likely to have a witnessed cardiac arrest, bystander-initiated cardiopulmonary resuscitation, or a "favorable" initial rhythm or to be admitted to the hospital. When they were admitted, blacks were half as likely to survive. The association between race and survival persisted even when other recognized risk factors were taken into account. We did not find important differences between blacks and whites in the response times of the emergency medical services. The black community in our study was at higher risk for cardiac arrest and subsequent death than the white community, even after we controlled for other variables.


A general one-pot strategy for the synthesis of high-performance transparent-conducting-oxide nanocrystal inks for all-solution-processed devices.
For all-solution-processed (ASP) devices, transparent conducting oxide (TCO) nanocrystal (NC) inks are anticipated as the next-generation electrodes to replace both those synthesized by sputtering techniques and those consisting of rare metals, but a universal and one-pot method to prepare these inks is still lacking. A universal one-pot strategy is now described; through simply heating a mixture of metal-organic precursors a wide range of TCO NC inks, which can be assembled into high-performance electrodes for use in ASP optoelectronics, were synthesized. This method can be used for various oxide NC inks with yields as high as 10 g. The formed NCs are of high crystallinity, uniform morphology, monodispersity, and high ink stability and feature effective doping. Therefore, the inks can be readily assembled into films with a surface roughness of 1.6 nm. Typically, a sheet resistance of 110 Ω sq(-1) can be achieved with a transmittance of 88%, which is the best performance for TCO NC ink-based electrodes described to date. These electrodes can thus drive a polymer light-emitting diode (PLED) with a luminance of 2200 cd m(-2) at 100 mA cm(-2).


Klinefelter's syndrome with renal tubular acidosis: impact on height.
A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature.


How common are non-acute coronary syndrome (ACS) diagnoses in patients with suspected ACS investigated with coronary angiography in New Zealand? (ANZACS-QI 58).
The last two decades in New Zealand have seen increased availability of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and early invasive coronary angiography (ICA) for other high-risk acute coronary syndrome (ACS) patients. One metric to assess the clinical appropriateness of these invasive strategies is to examine the false-positive rate for the investigation (ie, the rate of non-ACS diagnoses). All patients presenting to New Zealand public hospitals with suspected ACS who underwent ICA between 2015 and 2019 were recorded prospectively in the All New Zealand Acute Coronary Syndrome Quality Improvement registry. The cohort was divided according to clinical impression at presentation: (1) suspected STEMI <24h and (2) other suspected ACS. The final discharge diagnosis for each patient were obtained from the registry. There were 6,059 (20%) patients with suspected STEMI <24h and 24,258 (80%) with other suspected ACS. Of the suspected STEMIs <24h, 90.6% had a final diagnosis of STEMI, 3.5% non-ST segment elevation ACS (NSTEACS) and only 5.9% had a non-ACS diagnosis. Of those with other suspected ACS, 80.7% had a final ACS diagnosis. Across all New Zealand district health boards (DHBs), the proportion of non-ACS diagnoses was similar for suspected STEMI presentations. However, for other suspected ACS, the proportions were higher in DHBs with rapid access to coronary interventional facilities than in those without (17.6% vs 7.0%, p<0.001). False-positive catheter laboratory activations for suspected STEMI patients are low across New Zealand. The differences in the proportion of non-ACS diagnoses according to DHB interventional capability for other suspected ACS requires further investigation.


Breast tumor resembling the tall cell variant of papillary thyroid carcinoma: report of 4 cases with evidence of malignant potential.
A new type of breast carcinoma resembling the tall cell variant of papillary thyroid carcinoma has recently been described. To date, rare cases are on record. Here, 4 new cases of the tall cell variant of papillary thyroid carcinoma of the breast are described in women aged from 45 to 80 years old. All patients presented with palpable breast nodules and were treated with quadrantectomy. One patient presented with a long clinical history and a metastatic intramammary lymph node. The patient is alive and well 3 months after surgery. The remaining 3 patients are disease free at mean 7.5 months (range, 5 to 10 months) after surgery. These data suggest that papillary thyroid-like carcinomas of the breast show malignant potential.


A case of Déjerine-Sottas disease with schizophrenic symptoms. A clinical and pathological study.
A case of hypertrophic interstitial neuritis with a disturbance of intelligence and schizophrenic symptoms was reported. The patient, a 41-year-old male, showed monologia at the age of 14 and auditory hallucination at the age of 21. He was diagnosed as schizophrenia. Torsion of the head to the right side and muscular atrophy were also noticed at 21 years. Atrophy of the muscles progressed gradually, particularly in the distal parts of the upper and lower extremeties. Psychiatric examination revealed schizophrenic symptoms such as auditory hallucination, thought disorder, lack of spontaneity, autism, apathy, etc. There was also a disturbance of intelligence (imbecility). In neurological examination, the torsion of the head to the right side, slight exaggeration of the peripheral reflexes, muscular atrophy in the distal parts of the extremeties were noted. The bilateral ulnar nerves were markedly hypertrophied. The biopsy of the right ulnar nerve revealed a remarkable thickening of the endoneuria and "onion bulb" formations. A large amount of the interstitial accumulation of PAS positive substance, which showed metachromasia in cresyl violet staining, was also noted. Schwann cell processes were proved electron-microscopically to surround the myelin sheaths and some of them meandered and extended and into the metachromatic substance. The basement membrane of the sheath cell was hypertrophic in some portions and elongated into interstitium. The nucleus of the sheath cell was hyperchromic and showed marked atrophy. Histological examination of the biopsy specimen obtained from the gastrocnemius muscle suggested neurogenic muscular atrophy. The relationship among the hypertrophic interstitial neuritis, schizophrenic symptoms, disturbance of intelligence and torsion of the head was also discussed.


[The identification and sequence analysis of ALV-J isolated from layers].
Two Avian leukosis viruses of subgroup J (ALV-J) were isolated from layers by inoculating the sample into chicken embryo fibroblast (CEF) cells and by indirect fluorescent assay (IFA) with ALV-J specific monoclonal antibody JE-9. Sequence comparison indicated the gp85 identities were only in the ranges of 83.4%-87.3% compared with five international reference strains and 86.4%-89.6% compared with eight Chinese strains isolated from white meat-type chickens. The gp37 identities were in the range of 91.8-96.4% compared with the five international strains and 93.4-95.9% compared with the eight domestic strains. When compared with the above thirteen strains, two layers isolates were more close to the prototype HPRS-103 and had less deletion in 3'-Ter than those strains. All strains isolated from white meat-type chickens in China had a deletion in the "E" region of 3'-Ter except these two isolates, suggesting these two ALV-J isolates from layers have different evolution origins from other Chinese isolates from white meat-type chickens.


Synthesis and structure-activity relationship of methyl-substituted indolo[2,3-b]quinolines: novel cytotoxic, DNA topoisomerase II inhibitors.
In furtherance of our SAR study on the chemistry and antitumor activity of fused nitrogen heteroaromatic compounds, a series of linear, methyl-substituted derivatives of 5H- and 6H-indolo[2,3-b]quinolines were synthesized according to the modified Graebe-Ullmann reaction. To establish the relationship between the physicochemical and biological activities of indolo[2,3-b]quinolines, their lipophilic properties, cytotoxic and antimicrobial activity, and ability to induce topoisomerase II dependent pSP65 DNA cleavage in vitro were investigated. We found that the antimicrobial and cytotoxic activity of indolo[2,3-b]quinolines was strongly influenced by the position, and the number of methyl substituents and the presence of methyl group at pyridine nitrogen was essential for the cytotoxicity of these compounds. All indolo[2,3-b]quinolines belonging to the 5H series, i.e., bearing a methyl group on the pyridine nitrogen, showed significant activity against procaryotic and eucaryotic organisms. They inhibited the growth of Gram-positive bacteria and pathogenic fungi at MIC range 3 x 10(-2) to 2.5 x 10(-1) mumol/mL, displayed cytotoxicity against KB cells ID50 in the range 2 x 10(-3) to 9 x 10(-3) mumol/mL, and stimulated the formation of calf thymus topoisomerase II mediated DNA cleavage at concentration between 0.4 and 10 microM. None of the indolo[2,3-b]quinolines belonging to the 6H series, i.e., lacking a methyl group on the pyridine nitrogen, was active in analogous tests. Of the investigated compounds, the most active was 2,5,9,11-tetramethyl-5H-indolo[2,3-b]quinoline, a compound bearing the highest number of symmetrically distributed methyl groups. The interaction of indolo[2,3-b]quinolines with DNA was studied by measuring the increase of calf thymus DNA denaturating temperature (Tm). The delta Tm values for the 5H series were found to be about 10 times as high as those for the 6H compounds. Indolo[2,3-b]quinolines with the highest number of methyl groups had the greatest contribution to the increase in the Tm of calf thymus DNA. The values of delta Tm reached 19 degrees C and 1.6 degrees C for the most substituted compounds of both series.