Improving haematology care in Wales.
Care for patients with a malignant haematological disorder in Wales has been revised significantly since the mid-1990s. Recommendations from expert groups stated that a uniformly high standard of care should be provided as close to the patient's home as possible and variations in practice that had been causing concern and distress to patients and their families be reduced. The All Wales Haematology Nurses Group was established to promote and disseminate standards and guidelines that would contribute to achieving these aims. The basis for the group's work was transformational leadership and collaborative practice. Work is ongoing and the group is planning to consolidate achievements to date through country-wide audit and professional education.


Bioinspired nanofibers support chondrogenesis for articular cartilage repair.
Articular cartilage repair remains a significant and growing clinical challenge with the aging population. The native extracellular matrix (ECM) of articular cartilage is a 3D structure composed of proteinaceous fibers and a hydrogel ground substance that together provide the physical and biological cues to instruct cell behavior. Here we present fibrous scaffolds composed of poly(vinyl alcohol) and the biological cue chondroitin sulfate with fiber dimensions on the nanoscale for application to articular cartilage repair. The unique, low-density nature of the described nanofiber scaffolds allows for immediate cell infiltration for optimal tissue repair. The capacity for the scaffolds to facilitate cartilage-like tissue formation was evaluated in vitro. Compared with pellet cultures, the nanofiber scaffolds enhance chondrogenic differentiation of mesenchymal stems cells as indicated by increased ECM production and cartilage specific gene expression while also permitting cell proliferation. When implanted into rat osteochondral defects, acellular nanofiber scaffolds supported enhanced chondrogenesis marked by proteoglycan production minimally apparent in defects left empty. Furthermore, inclusion of chondroitin sulfate into the fibers enhanced cartilage-specific type II collagen synthesis in vitro and in vivo. By mimicking physical and biological cues of native ECM, the nanofiber scaffolds enhanced cartilaginous tissue formation, suggesting their potential utility for articular cartilage repair.


Mass spectrometry imaging as a tool for surgical decision-making.
Despite significant advances in image-guided therapy, surgeons are still too often left with uncertainty when deciding to remove tissue. This binary decision between removing and leaving tissue during surgery implies that the surgeon should be able to distinguish tumor from healthy tissue. In neurosurgery, current image-guidance approaches such as magnetic resonance imaging (MRI) combined with neuronavigation offer a map as to where the tumor should be, but the only definitive method to characterize the tissue at stake is histopathology. Although extremely valuable information is derived from this gold standard approach, it is limited to very few samples during surgery and is not practically used for the delineation of tumor margins. The development and implementation of faster, comprehensive, and complementary approaches for tissue characterization are required to support surgical decision-making--an incremental and iterative process with tumor removed in multiple and often minute biopsies. The development of atmospheric pressure ionization sources makes it possible to analyze tissue specimens with little to no sample preparation. Here, we highlight the value of desorption electrospray ionization as one of many available approaches for the analysis of surgical tissue. Twelve surgical samples resected from a patient during surgery were analyzed and diagnosed as glioblastoma tumor or necrotic tissue by standard histopathology, and mass spectrometry results were further correlated to histopathology for critical validation of the approach. The use of a robust statistical approach reiterated results from the qualitative detection of potential biomarkers of these tissue types. The correlation of the mass spectrometry and histopathology results to MRI brings significant insight into tumor presentation that could not only serve to guide tumor resection, but that is also worthy of more detailed studies on our understanding of tumor presentation on MRI.


Allergic contact dermatitis mimicking angioedema due to paraphenylendiamine hypersensitivity: a case report.
Active sensitization to paraphenylendiamine (PPD) and related compounds from temporary black henna tattoos has become an epidemic in the recent years. Hair dyes also include PPD like black henna tatoos which cause allergic contact dermatitis. Skin lesions of allergic contact dermatitis from PPD are mostly seen as an exudative erythema, an erythema multiforme-like eruption or a bullous contact dermatitis. We, herein, report a 27 year-old woman with an angioedema-like reaction occurring after the first exposure to hair dye who was unaware of being previously sensitized to PPD from black henna tattoo.


Health services research in anorexia nervosa.
The present paper reviews studies of the delivery of health services for individuals with anorexia nervosa, utilizing four interrelated concepts that guide much of health services research: equity, effectiveness, efficiency, and economy. It identifies major gaps in knowledge regarding health services utilization and costs.


Cost-Effectiveness of Lipid-Lowering Treatments in Young Adults.
Raised low-density lipoprotein cholesterol (LDL-C) in young adulthood (aged 18-39 years) is associated with atherosclerotic cardiovascular disease (ASCVD) later in life. Most young adults with elevated LDL-C do not currently receive lipid-lowering treatment. This study aimed to estimate the prevalence of elevated LDL-C in ASCVD-free U.S. young adults and the cost-effectiveness of lipid-lowering strategies for raised LDL-C in young adulthood compared with standard care. The prevalence of raised LDL-C was examined in the U.S. National Health and Nutrition Examination Survey. The CVD Policy Model projected lifetime quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios (ICERs) for lipid-lowering strategies. Standard care was statin treatment for adults aged ≥40 years based on LDL-C, ASCVD risk, or diabetes plus young adults with LDL-C ≥190 mg/dL. Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL. Approximately 27% of ASCVD-free young adults have LDL-C of ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL. The model projected that young adult lipid lowering with statins or lifestyle interventions would prevent lifetime ASCVD events and increase QALYs compared with standard care. ICERs were US$31,000/QALY for statins in young adult men with LDL-C of ≥130 mg/dL and US$106,000/QALY for statins in young adult women with LDL-C of ≥130 mg/dL. Intensive lifestyle intervention was more costly and less effective than statin therapy. Statin treatment for LDL-C of ≥130 mg/dL is highly cost-effective in young adult men and intermediately cost-effective in young adult women.


Advances in actinide thin films: synthesis, properties, and future directions.
Actinide-based compounds exhibit unique physics due to the presence of 5f electrons, and serve in many cases as important technological materials. Targeted thin film synthesis of actinide materials has been successful in generating high-purity specimens in which to study individual physical phenomena. These films have enabled the study of the unique electron configuration, strong mass renormalization, and nuclear decay in actinide metals and compounds. The growth of these films, as well as their thermophysical, magnetic, and topological properties, have been studied in a range of chemistries, albeit far fewer than most classes of thin film systems. This relative scarcity is the result of limited source material availability and safety constraints associated with the handling of radioactive materials. Here, we review recent work on the synthesis and characterization of actinide-based thin films in detail, describing both synthesis methods and modeling techniques for these materials. We review reports on pyrometallurgical, solution-based, and vapor deposition methods. We highlight the current state-of-the-art in order to construct a path forward to higher quality actinide thin films and heterostructure devices.


A "block and rescue" pharmacogenetic approach to dissecting a biochemical pathway controlling germ cell migration.
Specific small molecule inhibitors of the de novo cholesterol synthesis pathway (statins) and the protein prenylation pathway were used to study their effect on germ cell migration. Hydroxymethylglutaryl-Coenzyme A reductase (HMGCoAR) catalyzes the rate-limiting step in the mevalonate pathway that produces isoprenoids and cholesterol. Pharmacological HMGCoAR inhibition by statins alters zebrafish development and germ cell migration. These effects were completely blocked by prior injection of mevalonate, the product of HMGCoAR activity, or the prenylation precursors farnesol and geranylgeraniol. Finally, pharmacological inhibition of geranylgeranyl transferase I activity, an enzyme downstream from mevalonate synthesis and responsible for the transfer of a lipid to target proteins, resulted in abnormal germ cell migration. These data together with new data from Drosophila demonstrate that protein prenylation is an evolutionarily conserved pathway mediating germ cell migration. Further, pharmacological block-and-rescue approach provided detailed information about the elements of isoprenoid biosynthesis that contribute to germ cell migration. A key question raised by this work is the identity of the prenylated protein which facilitates proper germ cell migration. Work from other laboratories suggests that germ cell migration might be a general model for the long-range migration of other cell types including cancer metastasis.


[The problem of airtightness during the use of a laryngeal mask under conditions of carboperitoneum and muscle relaxation].
This study was aimed at assessing the airtightness of the airways during the use of a laryngeal mask (LM) under conditions of myoplegia and traditional forced ventilation of the lungs (FVL) with carboperitoneum (CP) during laparoscopic cholecystectomy (LCE). A total of 146 anesthesias for LCE were carried out using LM (n = 86) or endotracheal tube (ETT) (n = 60). The groups did not differ by the demographic characteristics or concomitant diseases. After premedication and induction of anesthesia it was maintained with N2O:O2--2/1 (Fi O2 = 0.3), fractionated administration of fentanyl (0.1-0.2 mg), and pipecuronium bromide (0.06 mg/kg). A gastric tube was inserted. Two variants of FVL were used: 1) permanent minute respiration volume (MRV) was maintained and 2) MRV was increased in order to maintain the Et CO2 at a constant level. The amount of gastric contents was measured and its pH assessed. Regurgitation and aspiration was assessed (in 33 patients) using methylene blue in gelatin capsules administered orally 10 min before anesthesia. Gas exchange was monitored by the Datex Capnomac-Ultima and by check-ups of acid base balance in the arterial capillary blood, hemodynamics was monitored by noninvasive Criticon Dynamap monitor. Manual FVL with inhalation P no more than 10 cm H2O completely prevented the entry of gas narcotic mixture into the stomach. Application of LM under conditions of total myoplegia and FVL with inhalation P of 23-25 cm H2O provided a satisfactory airtightness of the LM-airways contact without audible (appreciable) leaking of gas narcotic mixture. Leakage of gas narcotic mixture during LM application under total myoplegia and carboperitoneum (with CO2 pressure in the abdominal cavity 12 cm Hg) is no more than 6%, which indicates that LM is a reliable air guide providing good airtightness of the LM-airways contact even under conditions of increased abdominal pressure. No cases of regurgitation and aspiration were observed.


Ethylphenol Formation by Lactobacillus plantarum: Identification of the Enzyme Involved in the Reduction of Vinylphenols.
Ethylphenols are strong odorants produced by microbial activity that are described as off flavors in several foods. Lactobacillus plantarum is a lactic acid bacterial species able to produce ethylphenols by the reduction of vinylphenols during the metabolism of hydroxycinnamic acids. However, the reductase involved has not been yet uncovered. In this study, the involvement in vinylphenol reduction of a gene encoding a putative reductase (lp_3125) was confirmed by the absence of reduction activity in the Δlp_3125 knockout mutant. The protein encoded by lp_3125, VprA, was recombinantly produced in Escherichia coli VprA was assayed against vinylphenols (4-vinylphenol, 4-vinylcatechol, and 4-vinylguaiacol), and all were reduced to their corresponding ethylphenols (4-ethylphenol, 4-ethylcatechol, and 4-ethylguaiacol). PCR and high-performance liquid chromatography (HPLC) detection methods revealed that the VprA reductase is not widely distributed among the lactic acid bacteria studied and that only the bacteria possessing the vprA gene were able to produce ethylphenol from vinylphenol. However, all the species belonging to the L. plantarum group were ethylphenol producers. The identification of the L. plantarum VprA protein involved in hydroxycinnamate degradation completes the route of degradation of these compounds in lactic acid bacteria.IMPORTANCE The presence of volatile phenols is considered a major organoleptic defect of several fermented alcoholic beverages. The biosynthesis of these compounds has been mainly associated with Brettanomyces/Dekkera yeasts. However, the potential importance of lactic acid bacteria in volatile phenol spoilage is emphasized by reports describing a faster ethylphenol production by these bacteria than by yeasts. The genetic identification of the bacterial vinylphenol reductase involved in volatile phenol production provides new insights into the role of lactic acid bacteria in the production of these off flavors. The development of a molecular method for the detection of ethylphenol-producing bacteria could be helpful to design strategies to reduce the bacterial production of vinylphenols in fermented foods.


Gene mutations in the D-loop region of mitochondrial DNA in oral squamous cell carcinoma.
The present study aimed to investigate gene mutations in the displacement‑loop (D‑loop) region of mitochondrial DNA (mtDNA) in patients with oral squamous cell carcinoma (OSCC) in order to examine the role of gene mutation in mtDNA in OSCC tumorigenesis. mtDNA was obtained from cancer tissues, paracancerous tissues and normal mucosal tissues of thirty patients with OSCC. The D‑loop region of the mtDNA was amplified using polymerase chain reaction, sequenced and then analyzed by Chromas software and BLAST to identify the mutation sites. Mutations in the D‑loop region were observed in the cancer tissue samples of eight out of thirty cases with OSCC, with a mutation rate of 27%. There were nine mutations in total, including one point mutation, two base deletions, three insertion mutations and three heterozygous mutations. In these mutations, base deletions were different from each other and heterozygous mutations did not have the same mutation form; however, the three insertion mutations were the same, consisting of an insertion of a C base. One case contained a T/A heterozygous mutation as well as base insertion of C. The eight cases with mutations in the D‑loop region consisted of three cases of tongue cancer, two cases of soft palate cancer, one case of floor of the mouth cancer, one case of oropharyngeal cancer and one case of lip cancer. This study demonstrated mutations in the mtDNA D‑loop region in OSCC cells; however, the association between occurrences of OSCC and mtDNA mutations requires further investigation.


[Effects of Astragalus injection on renal tubular function in patients with IgA nephropathy].
To investigate the relationship between the renal tubular function and the severity of tubulo interstitial lesion and the effects of Astragalus Injection (AI) on renal tubular function in patients with IgA nephropathy (IgAN). Sixty-seven patients with IgAN were randomly divided into the control group and the astragalus group, both received dipyridamole and benazepril orally, while the astragalus group treated with AI by intravenous dripping additionally. The indices for renal tubular function, including protein in blood and urine, urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (UNAG), were detected. Area of glomerular Bowman capsule, renal tubules, and capillary were measured with color magic image analysis system type CMIAS2000. Urinary RBP and UNAG were correlated with tubulointerstitial lesion. Urine protein concentration decreased, blood albumin increased remarkably and renal tubular function improved after treatment in the astragalus group, with the improvement significantly different to those in the control group respectively. The severity of tubulointerstitial lesion was positively related to urinary RBP concentration, and astragalus injection has obvious effect on IgAN.


Co-ordinated detection of microparticles using tunable resistive pulse sensing and fluorescence spectroscopy.
Tunable resistive pulse sensing (TRPS) has emerged as a useful tool for particle-by-particle detection and analysis of microparticles and nanoparticles as they pass through a pore in a thin stretchable membrane. We have adapted a TRPS device in order to conduct simultaneous optical measurements of particles passing through the pore. High-resolution fluorescence emission spectra have been recorded for individual 1.9 μm diameter particles at a sampling period of 4.3 ms. These spectra are time-correlated with RPS pulses in a current trace sampled every 20 μs. The flow rate through the pore, controlled by altering the hydrostatic pressure, determines the rate of particle detection. At pressures below 1 kPa, more than 90% of fluorescence and RPS events were matching. At higher pressures, some peaks were missed by the fluorescence technique due to the difference in sampling rates. This technique enhances the particle-by-particle specificity of conventional RPS measurements and could be useful for a range of particle characterization and bioanalysis applications.


Loss of the SIN3 transcriptional corepressor results in aberrant mitochondrial function.
SIN3 is a transcriptional repressor protein known to regulate many genes, including a number of those that encode mitochondrial components. By monitoring RNA levels, we find that loss of SIN3 in Drosophila cultured cells results in up-regulation of not only nuclear encoded mitochondrial genes, but also those encoded by the mitochondrial genome. The up-regulation of gene expression is accompanied by a perturbation in ATP levels in SIN3-deficient cells, suggesting that the changes in mitochondrial gene expression result in altered mitochondrial activity. In support of the hypothesis that SIN3 is necessary for normal mitochondrial function, yeast sin3 null mutants exhibit very poor growth on non-fermentable carbon sources and show lower levels of ATP and reduced respiration rates. The findings that both yeast and Drosophila SIN3 affect mitochondrial activity suggest an evolutionarily conserved role for SIN3 in the control of cellular energy production.


Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis.
Stem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM. We pooled participant-level data from twenty-two eligible clinical trials that satisfied our inclusion criteria, with a total of 524 patients. There were significant differences in the outcome based on the type and source of the infused cells. Out of all T1DM patients who received CD34+ hematopoietic stem cell (HSC) infusion, 58.9% became insulin independent for a mean period of 16 months, whereas the results were uniformly negative in patients who received umbilical cord blood (UCB). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) provided significantly beneficial outcome in T1DM, when compared to bone-marrow mesenchymal stem cells (BM-MSCs) (P<0.0001 and P = 0.1557). Administration of stem cell therapy early after DM diagnosis was more effective than intervention at later stages (relative risk = 2.0, P = 0.0008). Adverse effects were observed in only 21.72% of both T1DM and T2DM stem cell recipients with no reported mortality. Out of all poor responders, 79.5% were diagnosed with diabetic ketoacidosis. Stem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34+ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.


[Indoor air pollution produced by man (carbon dioxide, odors)].
Man contributes to indoor air pollution by the release of heat, humidity, carbon dioxide, particles, micro-organisms and body odours. The rise in temperature and the concentrations of the different pollutants depend on the number of persons in a room, the utilization of the room and the activities of the persons. Current parameters for the evaluation of man-made pollution in indoor air are carbon monoxide and odours. Experiments have been carried out in a test chamber under controlled conditions in order to determine the relations between carbon monoxide and odours, since these are two current parameters for the evaluation of man-made pollution in indoor air. In these experiments the variables were the number of persons in the room, the activity of the persons and the ventilation rate. For the measurement of odours a special method has been developed in which the undiluted air is tested by a test panel and compared with air containing two different pyridine concentrations. A significant relationship has been observed between the odour intensity and the carbon dioxide content of the air, and the correlation did not depend on the number of persons and the ventilation rate. At ventilation rates of 12 to 15 m3 per person and hour the carbon dioxide concentration was below 0.15% and the odour intensity was characterized as being only little annoying. Higher ventilation rates are necessary during physical activity and in rooms with tobacco smoke. The minimum ventilation rates as deduced from the laboratory experiments are compared to known standards.


Pain relief in labor by transcutaneous electrical nerve stimulation. Testing of a modified stimulation technique and evaluation of the neurological and biochemical condition of the newborn infant.
In this prospective randomized study of pain relief in labor, the effect of transcutaneous electrical nerve stimulation (TNS) performed over both the low-back and suprapubic region was evaluated and compared with a control group not receiving TNS. Both high frequency and pulse train TNS were used. The study included 24 induced labors. In the TNS group, conventional methods were added when needed, while in the control group only conventional methods were used. Assessment of low-back and suprapubic pain was performed by the parturient each hour during the first stage. In the TNS group most of the parturients reported minimal or moderate low-back pain throughout labor, while parturients in the control group reported an increased intensity of low-back pain as labor progressed. The effect of suprapubic pain was insignificant in both groups. Neither TNS nor nitrous oxide-oxygen mixture and pethidine could reduce this pain component. Course of labor, uterine activity and fetal heart patterns were similar in the two groups. The neonates were evaluated with Apgar score, assays of blood samples from the umbilical vein including blood lactate, plasma hypoxanthine and blood gas, and neurobehavioral assessment on two occasions. All newborn infants were in good condition and no significant differences between the two groups could be demonstrated.


Impaired neurocognitive functions affect social learning processes in oppositional defiant disorder and conduct disorder: implications for interventions.
In this review, a conceptualization of oppositional defiant (ODD) and conduct disorder (CD) is presented according to which social learning processes in these disorders are affected by neurocognitive dysfunctions. Neurobiological studies in ODD and CD suggest that the ability to make associations between behaviors and negative and positive consequences is compromised in children and adolescents with these disorders due to reduced sensitivity to punishment and to reward. As a result, both learning of appropriate behavior and learning to refrain from inappropriate behavior may be affected. Likewise, problem solving is impaired due to deficiencies in inhibition, attention, cognitive flexibility, and decision making. Consequently, children and adolescents with ODD and CD may have difficulty learning to optimize their behavior in changeable environments. This conceptualization of ODD and CD is relevant for the improvement of the effect of psychological treatments. Behavioral and cognitive-behavioral interventions that have been shown to be modestly effective in ODD and CD are based on social learning. Limited effectiveness of these interventions may be caused by difficulties in social learning in children and adolescents with ODD and CD. However, although these impairments have been observed at a group level, the deficits in reward processing, punishment processing, and cognitive control mentioned above may not be present to the same extent in each individual with ODD and CD. Therefore, the neurocognitive characteristics in children and adolescents with ODD and CD should be assessed individually. Thus, instead of delivering interventions in a standardized way, these programs may benefit from an individualized approach that depends on the weaknesses and strengths of the neurocognitive characteristics of the child and the adolescent.


Monaural and binaural inhibition underlying duration-tuned neurons in the inferior colliculus.
Duration-tuned neurons (DTNs) in the mammalian inferior colliculus (IC) arise from a combination of excitatory and inhibitory synaptic inputs. Previous research has shown that the inhibition responsible for creating DTNs has a shorter latency than that of excitation and lasts longer than the stimulus duration. We used monotic and dichotic paired tone stimulation and recorded responses of DTNs from the IC of the bat to assess the relative contributions of each ear in forming duration-tuned circuits. The stimulus consisted of a short best duration (BD) excitatory tone and a longer duration nonexcitatory (NE) tone. In the monotic condition, when the BD and NE tones were presented to the contralateral ear and were sufficiently close in time, the NE tone always suppressed spikes evoked by the BD tone. In the dichotic condition, when the BD tone was presented to the contralateral ear and the NE tone to the ipsilateral ear, half of DTNs no longer showed spike suppression to the NE tone. Of those DTNs with suppression in both conditions, the latency of the inhibition was shorter and the duration of the inhibition was longer in the monotic condition. Therefore, in the monotic condition, DTNs received a contralaterally evoked inhibitory input that preceded the excitatory input to the same neuron. In the dichotic condition, DTNs received an ipsilaterally evoked inhibitory input that was weaker, longer in latency, and shorter in duration than the inputs from the contralateral ear. These findings indicate that the neural mechanisms that create DTNs in the IC are monaural.


Drusen characteristics of type 2 macular neovascularization in age-related macular degeneration.
Type 2 macular neovascularization (MNV) is supposed to be a rare condition in age-related macular degeneration (AMD). The main purpose of this study was to assess accompanying factors of type 2 MNV in AMD. Retrospective data analysis of eyes previously diagnosed with neovascular AMD in a tertiary eye care center (Medical Retina Unit, Rudolf Foundation Hospital, Vienna, Austria) between June 2008 and December 2017. Drusen subtypes, fibrosis, atrophy and subfoveal choroidal thickness (SFCT) of both eyes in patients with type 2 MNV lesions were categorized based on multimodal imaging. Type 2 MNV was diagnosed in 27 (3.2%) of 835 eyes (749 patients). Drusen characteristics in type 2 MNV were observed as followed: drusen < 63 μm in 2 eyes (7.4%), drusen ≥63 μm in 10 eyes (37%), subretinal drusenoid deposits (SDD) in 8 eyes (29.6%), cuticular drusen in 2 eye (7.4%) and no drusen were evident in 10 eyes (37%). Drusen distribution in 23 fellow eyes was detected as followed: drusen < 63 μm in 2 eyes (8.7%), drusen ≥63 μm in 9 eyes (39.1%), SDD in 5 eyes (21.7%), cuticular drusen in 1 eye (4.3%) and no drusen were evident in 9 eyes (39.1%). Mean SFCT was 140 ± 49 μm in affected eyes and 152 ± 41 μm in the fellow eyes. Patients with drusen or SDD were significantly younger (mean 70.88 ± 6.85, p = 0.04) than patients without deposits (mean 77.40 ± 5.74). Type 2 MNV remains a rare entity in AMD. It was frequently seen in the absence of drusen, a hallmark of AMD. These findings contribute to the heterogeneity of phenotypes related to pure type 2 lesions.


Cytotoxic activity of 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (mitotane) and its analogs on feminizing adrenal neoplastic cells in culture.
Mitotane [1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane], an antineoplastic agent for inoperable adrenal carcinoma, was studied for its cytotoxic activity on a clonal line of feminizing human adrenal neoplastic cells (Fang-8 cells) in culture. At concentrations higher than 1.68 X 10(-4) M, mitotane produced a dose-related toxic effect on the cells. The effect of the drug was specific to Fang-8 cells because the same treatment produced little or no toxicity on lines of rat pituitary GH3 cells and human skin fibrocytes. The effect of mitotane to Fang-8 cells was a reversible one. Electron microscopic pictures revealed that the drug was causing mitochondrial degeneration. In this testing system, several isomers and analogs of mitotane were found equally or more toxic than was mitotane itself. The dichloro- or trichloroethylene structure was essential for the cytotoxic activity while the chloro substituents on phenyl rings appeared to be unimportant. This system appears to be useful in elucidating the biochemical mechanism of mitotane action on adrenal cancer.


Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma.
Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.


Stress, strain and deformation of poly-lactic acid filament deposited onto polyethylene terephthalate woven fabric through 3D printing process.
Although direct deposition of polymeric materials onto textiles through 3D printing is a great technique used more and more to develop smart textiles, one of the main challenges is to demonstrate equal or better mechanical resistance, durability and comfort than those of the textile substrates before deposition process. This article focuses on studying the impact of the textile properties and printing platform temperature on the tensile and deformations of non-conductive and conductive poly lactic acid (PLA) filaments deposited onto polyethylene terephthalate (PET) textiles through 3D printing process and optimizing them using theoretical and statistical models. The results demonstrate that the deposition process affects the tensile properties of the printed textile in comparison with the ones of the textiles. The stress and strain at rupture of the first 3D printed PLA layer deposited onto PET textile material reveal to be a combination of those of the printed layer and the PET fabric due to the lower flexibility and diffusion of the polymeric printed track through the textile fabric leading to a weak adhesion at the polymer/textile interface. Besides, printing platform temperature and textile properties influence the tensile and deformation properties of the 3D printed PLA on PET textile significantly. Both, the washing process and the incorporation of conductive fillers into the PLA do not affect the tensile properties of the extruded polymeric materials. The elastic, total and permanent deformations of the 3D-printed PLA on PET fabrics are lower than the ones of the fabric before polymer deposition which demonstrates a better dimensional stability, higher stiffness and lower flexibility of these materials.


Dental caries prevalence among HIV adult population in India: A systematic review.
Dental caries is a universal disease. Untreated dental caries adds to the existing burden of diseases. It is necessary to have national data on the same, especially in HIV cases, to understand the epidemiological aspects and formulate a treatment plan for the population. Hence, a systematic review was carried out to collectively report the dental caries prevalence among this population. A systematic search for articles was done in PubMed and Google Scholar using the keywords: Dental Caries, India, HIV, AIDS and adults from January 1990 to December 2019. All freely available full-text articles were evaluated based on the inclusion criteria. Only four articles fulfilled the criteria based on qualitative analysis. Decayed, Missing and Filled Teeth index was used to record dental caries. Risk factors related to the same were not specified by any of the authors. Studies were not from different regions of India. More epidemiological studies are needed to understand the prevalence rate and correlated to dental caries among HIV-positive population in India.


The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it.
Filamin A (FlnA) has been associated with actin as cytoskeleton regulator. Recently its role in the cell has come under scrutiny for FlnA's involvement in cancer development. FlnA was originally revealed as a cancer-promoting protein, involved in invasion and metastasis. However, recent studies have also found that under certain conditions, it prevented tumor formation or progression, confusing the precise function of FlnA in cancer development. Here, we try to decipher the role of FlnA in cancer and the implications for its dual role. We propose that differences in subcellular localization of FlnA dictate its role in cancer development. In the cytoplasm, FlnA functions in various growth signaling pathways, such as vascular endothelial growth factor, in addition to being involved in cell migration and adhesion pathways, such as R-Ras and integrin signaling. Involvement in these pathways and various others has shown a correlation between high cytoplasmic FlnA levels and invasive cancers. However, an active cleaved form of FlnA can localize to the nucleus rather than the cytoplasm and its interaction with transcription factors has been linked to a decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a tumor-promoting effect, only when it is localized to the cytoplasm, whereas if FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of drugs to target FlnA and cause cleavage and subsequent localization to the nucleus could be a new and potent field of research in treating cancer.


Involvement of capsaicin-sensitive nerves in regulating the hormone and glucose metabolic response to endotoxin.
This study investigated the role that sensory nerves play in mediating the hormone and glucose metabolic response to endotoxin [lipopolysaccharide (LPS)]. Adult rats were pretreated subcutaneously with capsaicin to selectively destroy primary sensory afferent nerve fibers. Ten days later, [3-3H]glucose was infused intravenously to assess whole body glucose flux before and after the intravenous injection of Escherichia coli LPS (100 micrograms/100 g body wt). Control animals responded to LPS with characteristic increases in the plasma concentration of glucose (91%) and lactate (threefold) and elevations in the rates of glucose appearance and disappearance (77%). In capsaicin-treated rats, the maximal LPS-induced increase in these parameters was attenuated by 50-60%. In addition, these animals were hypoglycemic at the conclusion of the experiment. Control animals demonstrated early and sustained elevations in circulating levels of corticosterone, glucagon, and catecholamines. In contrast, the early LPS-induced elevation in epinephrine and norepinephrine, and to a lesser extent glucagon, was completely absent or greatly impaired by capsaicin pretreatment. In a separate study, the epinephrine-induced increase in glucose flux was blunted by 75% in capsaicin-treated rats. These data indicate that sensory afferent neurons play a critical role in the early secretory response of glucagon and catecholamines, the maintenance of tissue catecholamine responsiveness, and the stimulation of glucose production after LPS.


The effect of monopolar radiofrequency treatment pattern on joint capsular healing. In vitro and in vivo studies using an ovine model.
The purpose of this study was to compare joint capsular healing after two delivery patterns of monopolar radiofrequency energy: 1) uniform treatment of the joint capsule (paintbrush pattern) and 2) multiple single linear passes (grid pattern). First, an in vitro study was performed to compare the percent shrinkage of these two treatment patterns using the femoropatellar joints (stifles) of six sheep. Monopolar radiofrequency energy (settings, 70 degrees C/15W) was applied to the lateral joint capsule; the treated area was approximately 10 x 10 mm. There was no significant difference in shrinkage between the grid (27% +/- 8.7%) and paintbrush (29% +/- 7.9%) patterns. In the in vivo study, stifles of 24 sheep were randomly assigned to the paintbrush or the grid pattern groups and treatment was performed arthroscopically. Sheep were sacrificed immediately after surgery, or at 2, 6, or 12 weeks after surgery. At 6 weeks after surgery, confocal microscopy demonstrated that treated areas had almost completely repaired in the grid group; some nonviable areas were still present in the paintbrush group. Mechanical testing at 6 weeks indicated that joint capsule in the grid group had better mechanical properties than capsule in the paintbrush group. This study revealed that radiofrequency treatment of joint capsule in a grid pattern allowed faster healing than tissue treated in a paintbrush pattern.


Space plasma physics: atmospheric emissions photometric imaging experiment.
The atmospheric emissions photometric imaging experiment was flown on Spacelab 1 to study faint natural and artificial atmospheric emission phenomena. The instrument imaged optical emission in the region 2000 to 7500 angstroms with a television system consisting of two optical channels, one wide-angle and one telephoto. A third optical channel imaged onto the photochathode of a microchannel plate photomultiplier tube that has 100 discrete anodes. A hand-held image intensifier camera with an objective grating permitted spectral analysis of the earth's airglow and the shuttle glow. Preliminary data show magnesium ion emission features in the lower ionosphere as well as the spececraft glow spectrum.


Molecular architecture of SMC proteins and the yeast cohesin complex.
Sister chromatids are held together by the multisubunit cohesin complex, which contains two SMC (Smc1 and Smc3) and two non-SMC (Scc1 and Scc3) proteins. The crystal structure of a bacterial SMC "hinge" region along with EM studies and biochemical experiments on yeast Smc1 and Smc3 proteins show that SMC protamers fold up individually into rod-shaped molecules. A 45 nm long intramolecular coiled coil separates the hinge region from the ATPase-containing "head" domain. Smc1 and Smc3 bind to each other via heterotypic interactions between their hinges to form a V-shaped heterodimer. The two heads of the V-shaped dimer are connected by different ends of the cleavable Scc1 subunit. Cohesin therefore forms a large proteinaceous loop within which sister chromatids might be entrapped after DNA replication.


Mother's Infant and Young Child Feeding (IYCF) knowledge improved timely initiation of complementary feeding of children aged 6-24 months in the rural population of northwest Ethiopia.
Appropriate complementary feeding is vital to reduce young child morbidity and mortality. However, it continues as sub-optimal in Ethiopia, and literatures are also scarce. Therefore, this study aimed to determine timely initiation of complementary feeding and associated factors among mothers with children aged 6-24 months in the rural population of northwest Ethiopia. In the community based cross-sectional study, data on child feeding practices, individual and household characteristics were collected in Dabat Demographic Surveillance System site, Dabat District, northwest Ethiopia from 01 May to 29 June 2015. The bivariate and backward stepwise multivariable statistical methods were carried out to identify factors associated with timely initiation of complementary feeding. About 53.8% [95% CI 45.9, 61.7] and 4.6% [95% CI 1.3, 7.9] of children were found with timely initiation of complementary feeding and had minimum dietary diversity, respectively. The odds of timely initiation of complementary feeding was higher among mothers with medium [AOR = 2.34, 95% CI 1.54, 3.81] and high [AOR = 2.10, 95% CI 1.41, 3.87] mother's IYCF knowledge. In Dabat district, complementary feeding practice is lower. Thus, efforts should be strengthened to boost mother's IYCF knowledge.


Engineering the redox potential over a wide range within a new class of FeS proteins.
MitoNEET is a newly discovered mitochondrial protein and a target of the TZD class of antidiabetes drugs. MitoNEET is homodimeric with each protomer binding a [2Fe-2S] center through a rare 3-Cys and 1-His coordination geometry. Both the fold and the coordination of the [2Fe-2S] centers suggest that it could have novel properties compared to other known [2Fe-2S] proteins. We tested the robustness of mitoNEET to mutation and the range over which the redox potential (E(M)) could be tuned. We found that the protein could tolerate an array of mutations that modified the E(M) of the [2Fe-2S] center over a range of ∼700 mV, which is the largest E(M) range engineered in an FeS protein and, importantly, spans the cellular redox range (+200 to -300 mV). These properties make mitoNEET potentially useful for both physiological studies and industrial applications as a stable, water-soluble, redox agent.


Exploring organic matter conversion pathway and its effect on nitrogen removal in tidal flow constructed wetlands.
Achieving effective nitrogen removal remains a significant challenge faced by constructed wetlands. Although organic matter is a crucial factor influencing nitrogen removal, little attention has been paid to the impact of organic matter conversion pathways on nitrogen removal in constructed wetlands. Here, we showed that endogenous microorganisms performing carbon internalization could be easily enriched in tidal flow constructed wetlands (TFCWs) under its special rhythmic cycle of anaerobic/aerobic operational mode. Endogenous microorganisms could translate influent carbon sources into intracellular carbons during the anaerobic stage and supply the carbon source for endogenous denitrification after the aerobic stage (rest period). Based on these findings, an innovative combined TFCW and Nitrifying-CW system was developed, and robust total nitrogen (TN) removal (82% on average) was achieved even under carbon source limiting conditions. This performance was a substantial improvement compared to the conventional single bed TFCW with multiple "tides" (corresponding to the multiple contact/rest periods) with TN removal of only 54% on average. Simultaneous nitrification-endogenous denitrification (SNED) was found to be the major nitrogen removal pathway in the proposed system. Compared with classical nitrification-denitrification, simultaneous nitrification-endogenous denitrification brings high nitrogen conversion rates and significantly reduces the demand for oxygen and organic carbon. Furthermore, microbial community analysis indicated that endogenous microorganisms such as Candidatus_Competibacter and Defluviicoccus were successfully enriched, accounting for 50.73% and 3.46% in CW1, and 25.25% and 1.76% in CW2, respectively. Together, these mechanisms allow the proposed system to achieve efficient TN removal.


The isolated supported canine heart: a model for the evaluation of drug effects on regional myocardial blood flow.
The effect of independently varying heart rate, left ventricular systolic pressure, coronary blood flow or coronary artery perfusion pressure on the transmural distribution of myocardial blood flow was determined in the isolated supported dog heart preparation by use of radioactive microspheres. The distribution of radioactivity was expressed as the epicardial/endocardial blood flow ratio (epi/endo). At a constant coronary blood flow, increases in heart rate (111-250 beats/min) or decreases in coronary artery perfusion pressure (100-46 mm Hg) resulted in an elevation of epi/endo (0.64 to 1.12 and 0.71 to 1.41, respectively). Increasing coronary artery perfusion pressure (40-130 mm Hg) and coronary blood flow from low values resulted in a decreased epi/endo (1.28 to 0.76). The absolute level of coronary blood flow had no direct effect on epi/endo but acted through changes in coronary artery perfusion pressure. The major physiological determinants of intramyocardial blood flow distribution in the isolated dog heart are coronary artery perfusion pressure and heart rate, whereas left ventricular systolic pressure and coronary blood flow are of minor importance. An equation was developed relating the mean epi/endo of the left ventricle to hemodynamic factors studied, and a highly significant correlation was found between predicted and experimental ratios. These results indicate the potential usefulness of this model for predicting epicardial-endocardial blood flow ratios based upon drug-induced changes in hemodynamic parameters.


Toward collaborative open data science in metabolomics using Jupyter Notebooks and cloud computing.
A lack of transparency and reporting standards in the scientific community has led to increasing and widespread concerns relating to reproduction and integrity of results. As an omics science, which generates vast amounts of data and relies heavily on data science for deriving biological meaning, metabolomics is highly vulnerable to irreproducibility. The metabolomics community has made substantial efforts to align with FAIR data standards by promoting open data formats, data repositories, online spectral libraries, and metabolite databases. Open data analysis platforms also exist; however, they tend to be inflexible and rely on the user to adequately report their methods and results. To enable FAIR data science in metabolomics, methods and results need to be transparently disseminated in a manner that is rapid, reusable, and fully integrated with the published work. To ensure broad use within the community such a framework also needs to be inclusive and intuitive for both computational novices and experts alike. To encourage metabolomics researchers from all backgrounds to take control of their own data science, mould it to their personal requirements, and enthusiastically share resources through open science. This tutorial introduces the concept of interactive web-based computational laboratory notebooks. The reader is guided through a set of experiential tutorials specifically targeted at metabolomics researchers, based around the Jupyter Notebook web application, GitHub data repository, and Binder cloud computing platform.


Risk factors for nonunion in patients with transcondylar fracture of the distal humerus after open reduction and internal fixation.
Transcondylar fractures have been reported to rarely occur in the distal humerus, and stable fixation is difficult because of the unique fracture pattern. However, few studies have reported the risk factors for nonunion after open reduction and internal fixation (ORIF). This study aimed to evaluate the demographic and surgical risk factors for nonunion in patients who had undergone ORIF for transcondylar fractures. We retrospectively reviewed 68 patients who underwent ORIF for transcondylar fractures. Preoperative demographic factors, including diabetes mellitus (DM) and smoking, and operative factors, including fixation methods (eg, dual plate/single plate/tension band wiring [TBW]) were assessed as risk factors for nonunion. Nonunion occurred in 8 out of 68 patients (11.8%). Univariate analysis revealed that among the demographic factors, DM (4/8 [50%] vs. 8/60 [13.3%], P = .028) and smoking (3/8 [37.5%] vs. 4/60 [6.7%], P = .031) were significantly different between nonunion and union patients. Regarding operative factors, the fixation method (dual plate/single plate/TBW; 2 [25.0%]/2 [25.0%]/4 [50%] vs. 29 [48.3%]/25 [41.7%]/6 [10.0%], P = .033) showed significant differences between nonunion and union patients. Multivariate regression analysis showed that DM (odds ratio [OR], 10.560; 95% confidence interval [CI], 1.308-85.247; P = .027), smoking (OR 22.371; 95% CI, 2.111-237.081; P = .010), and TBW (OR 15.390; 95% CI, 1.348-175.666; P = .028) were independent risk factors for nonunion. Nonunion occurred in approximately 12% of the patients who underwent ORIF in the transcondylar region of the distal humerus. The risk of nonunion was higher in patients with DM than those who smoked. In addition, among the fixation methods, the TBW technique was a significant risk factor for nonunion.


Evolutionarily dynamic roles of a PUF RNA-binding protein in the somatic development of Caenorhabditis briggsae.
Gene duplication and divergence has emerged as an important aspect of developmental evolution. The genomes of Caenorhabditis nematodes encode an ancient family of PUF RNA-binding proteins. Most have been implicated in germline development, and are often redundant with paralogs of the same sub-family. An exception is Cbr-puf-2 (one of three Caenorhabditis briggsae PUF-2 sub-family paralogs), which is required for development past the second larval stage. Here, we provide a detailed functional characterization of Cbr-puf-2. The larval arrest of Cbr-puf-2 mutant animals is caused by inefficient breakdown of bacterial food, which leads to starvation. Cbr-puf-2 is required for the normal grinding cycle of the muscular terminal bulb during early larval stages, and is transiently expressed in this tissue. In addition, rescue of larval arrest reveals that Cbr-puf-2 also promotes normal vulval development. It is expressed in the anchor cell (which induces vulval fate) and vulval muscles, but not in the vulva precursor cells (VPCs) themselves. This contrasts with the VPC-autonomous repression of vulval development described for the Caenorhabditis elegans homologs fbf-1/2. These different roles for PUF proteins occur even as the vulva and pharynx maintain highly conserved anatomies across Caenorhabditis, indicating pervasive developmental system drift (DSD). Because Cbr-PUF-2 shares RNA-binding specificity with its paralogs and with C. elegans FBF, we suggest that functional novelty of RNA-binding proteins evolves through changes in the site of their expression, perhaps in concert with cis-regulatory evolution in target mRNAs.


Clinical practice guidelines for evidence-based management of sedoanalgesia in critically ill adult patients.
Optimal management of sedation, analgesia and delirium offers comfort and security for the critical care patient, allows support measures to be applied more easily and enables an integral approach of medical care, at the same time that lowers the incidence of complications, wich translates in better patient outcomes. To update the Guía de práctica clínica basada en la evidencia para el manejo de la sedoanalgesia en el paciente adulto críticamente enfermo published in Medicina Intensiva in 2007, and give recommendations for the management of sedation, analgesia, and delirium. A group of 21 intensivists from 9 countries of the Federación Panamericana e Ibérica de Sociedades de Medicina Crítica y Terapia Intensiva, 3 of them also specialists in clinical epidemiology and methodology, gathered for the development of guidelines. Assessment of evidence quality and recommendations were made based on the Grading of Recommendations Assessment, Development and Evaluation system. Strength of recommendations was classified as 1=strong, or 2=weak, and quality of evidence as A=high, B=moderate, or C=low. Two authors searched the following databases: MEDLINE through PUBMED, The Cochrane Library and Literatura Latinoamericana y del Caribe en Ciencias de la Salud and retrieved pertinent information. Members assigned to the 11 sections of the guidelines, based on the literature review, formulated the recommendations, that were discussed in plenary sessions. Only those recommendations that achieved more than 80% of consensus were approved for the final document. The Colombian Association of Critical Medicine and Intensive Care (AMCI) supported the elaboration of this guidelines. Four hundred sixty-seven articles were included for review. An increase in number and quality of publications was observed. This allowed to generate 64 strong recommendations with high and moderate quality of evidence in contrast to the 28 recommendations of the previous edition. This Guidelines contains recommendations and suggestions based on the best evidence available for the management of sedation, analgesia and delirium of the critically ill patient, including a bundle of strategies that serves this purpose. We highlight the assessment of pain and agitation/sedation through validated scales, the use of opioids initially to apropiate analgesic control, associated with multimodal strategies in order to reduce opioide consumption; to promote the lowest level of sedation necessary avoiding over-sedation. Also, in case of the need of sedatives, choose the most appropiate for the patient needs, avoiding the use of benzodiazepines and identify risk factors for delirium, in order to prevent its occurrence, diagnose delirium and treat it with the most suitable pharmacological agent, whether it is haloperidol, atypical antipsychotics or dexmedetomidine, once again, avoiding the use of benzodiazepines and decreasing the use of opioids.


[Clinical course and causes of death in patients with HIV/AIDS-associated tuberculosis].
It was determined that most of the patients with HIV/AIDS-associated tuberculosis were antisocial way of life. There were more causes of newly diagnosed tuberculosis and drug resistance tuberculosis among the dead cases of HIV/AIDS-associated tuberculosis. Tuberculosis more often had started after HIV-infection. In patients who died of co-infection disseminated and infiltrative forms of pulmonary tuberculosis were determined more often. Death came more often from progression of disseminated pulmonary tuberculosis. Most patients had no commitment to a specific anti-TB and antiretroviral treatment.


Sulfate Cooling Effect on Climate Through In-Cloud Oxidation of Anthropogenic SO2.
Anthropogenic SO(2) emissions may exert a significant cooling effect on climate in the Northern Hemisphere through backscattering of solar radiation by sulfate particles. Earlier estimates of the sulfate climate forcing were based on a limited number of sulfate-scattering correlation measurements from which a high sulfate-scattering efficiency was derived. Model results suggest that cloud processing of air is the underlying mechanism. Aqueous phase oxidation of SO(2) into sulfate and the subsequent release of the dry aerosol by cloud evaporation render sulfate a much more efficient scatterer than through gas-phase SO(2) oxidation.


Selective coverage of the left subclavian artery without revascularization in patients with bilateral patent vertebrobasilar junctions during thoracic endovascular aortic repair.
The primary purpose of the current study was to evaluate the safety and effectiveness of selective coverage of the left subclavian artery (LSCA) without revascularization during thoracic endovascular aortic repair (TEVAR) in patients with bilateral patent vertebrobasilar junctions. The secondary purpose was to assess morphologic change of the vertebral artery (VA) after the procedure. Among 126 patients who underwent TEVAR between 2006 and 2011, 29 patients requiring LSCA coverage without preemptive revascularization were retrospectively analyzed in this study. The patients were a mean age of 63.1 years (range, 45-84 years). The mean follow-up period was 19.9 months (range, 1-63 months). Bilateral patent vertebrobasilar junctions were evaluated by contrast-enhanced computed tomography (CT), time-of flight magnetic resonance angiography, or conventional angiography. Neurologic complications, such as spinal cord ischemia (SCI) or cerebrovascular accidents, were analyzed. Preprocedural and postprocedural changes in VAs were evaluated on follow-up contrast-enhanced CT. The overall 30-day mortality was 6.9% (2 of 29). None of the patients had SCI or a stroke of posterior circulation alone. Cerebrovascular accidents from embolic infarctions occurred in two patients (7.4%). Transient left arm ischemic symptoms were present in five patients (18.5%), but none required secondary interventions. Delayed development of type I endoleak occurred due to stent deformity in one patient, who underwent surgery. One patient required reintervention after the 10-month follow-up contrast-enhanced CT showed a pseudoaneurysm had developed at the distal margin of the previously placed stent graft. Hypertrophy of the right VA after TEVAR was seen in seven of 27 patients (25.9%); two patients showed bilateral hypertrophy of VAs. LSCA coverage without revascularization can be safely performed during TEVAR in patients with bilateral patent vertebrobasilar junctions. Hypertrophy of the right VA was noted in 25.9% of patients after LSCA coverage.


[Estrogen feedback tests in women with laryngeal carcinomas].
The high incidence ratio males to females is the reason for considering a hormonal dependency of these tumours for many years. The low incidence of laryngeal cancer in women has generally been suggested as being due to "oestrogen defense". Although we do have some circumstantial evidence in the meantime, no final evidence on this topic is available so far. The oestrogen feedback effect could be another more objective parameter to bring more light to the research of this question. As one of the regulation mechanisms of the hypothalamic-pituitary-adrenal axis the oestrogen feedback mechanism represents the regulation of LH and FSH production in the pituitary gland by peripheral oestrogens. The mechanism is known to exist lifelong under normal conditions. Whereas the positive oestrogen feedback is typical for women, a negative response pattern is mostly found in men. The positive response pattern is characterised by increasing LH values, higher than the starting level, on the 3 th and 4 th day after intravenious application of oestrogens. The results of the present investigation show some difference. 5 of 6 examined women with laryngeal cancer were found to have a clearly negative oestrogen feedback, whereas 4 of 5 healthy women had a positive oestrogen feedback effect. 5 healthy men showed the typical negative effect for men. We may assume a narrow relationship between the male regulation type and the occurrence of laryngeal cancer in women, if further trials including more patients are able to reproduce these results.


Effect of the side-chain-distribution density on the single-conjugated-polymer-chain conformation.
The spatial arrangement of the side chains of conjugated polymer backbones has critical effects on the morphology and electronic and photophysical properties of the corresponding bulk films. The effect of the side-chain-distribution density on the conformation at the isolated single-polymer-chain level was investigated with regiorandom (rra-) poly(3-hexylthiophene) (P3HT) and poly(3-hexyl-2,5-thienylene vinylene) (P3HTV). Although pure P3HTV films are known to have low fluorescence quantum efficiencies, we observed a considerable increase in fluorescence intensity by dispersing P3HTV in poly(methyl methacrylate) (PMMA), which enabled a single-molecule spectroscopy investigation. With single-molecule fluorescence excitation polarization spectroscopy, we found that rra-P3HTV single molecules form highly ordered conformations. In contrast, rra-P3HT single molecules, display a wide variety of different conformations from isotropic to highly ordered, were observed. The experimental results are supported by extensive molecular dynamics simulations, which reveal that the reduced side-chain-distribution density, that is, the spaced-out side-chain substitution pattern, in rra-P3HTV favors more ordered conformations compared to rra-P3HT. Our results demonstrate that the distribution of side chains strongly affects the polymer-chain conformation, even at the single-molecule level, an aspect that has important implications when interpreting the macroscopic interchain packing structure exhibited by bulk polymer films.


Energy-containing beverages: reproductive hormones and ovarian function in the BioCycle Study.
Energy-containing beverages are widely consumed among premenopausal women, but their association with reproductive hormones is not well understood. The objective was to assess the association of energy-containing beverages, added sugars, and total fructose intake with reproductive hormones among ovulatory cycles and sporadic anovulation in healthy premenopausal women. Women (n = 259) in the BioCycle Study were followed for up to 2 menstrual cycles; they provided fasting blood specimens during up to 8 visits/cycle and four 24-h dietary recalls/cycle. Women who consumed ≥1 cup (1 cup = 237 mL) sweetened soda/d had 16.3% higher estradiol concentrations compared with women who consumed less sweetened soda (86.5 pg/mL compared with 74.4 pg/mL, P = 0.01) after adjustment for age, BMI, race, dietary factors, and physical activity. Similarly elevated estradiol concentrations were found for ≥1 cup cola/d and noncola soda intake. Neither artificially sweetened soda nor fruit juice intake ≥1 cup/d was significantly associated with reproductive hormones. Added sugar above the average US woman's intake (≥73.2 g/d) or above the 66th percentile in total fructose intake (≥41.5 g/d) was associated with significantly elevated estradiol but not consistently across all models. No associations were found between beverages, added sugars, or total fructose intake and anovulation after multivariate adjustment. Even at moderate consumption amounts, sweetened soda is associated with elevated follicular estradiol concentrations among premenopausal women but does not appear to affect ovulatory function. Further research into the mechanism driving the association between energy-containing beverages and reproductive hormones, and its potential implications for women's health, is warranted.


Gravity-dominated Collisions: A Model for the Largest Remnant Masses with Treatment for "Hit and Run" and Density Stratification.
We develop empirical relationships for the accretion and erosion of colliding gravity-dominated bodies of various compositions under conditions expected in late-stage solar system formation. These are fast, easily coded relationships based on a large database of smoothed particle hydrodynamics (SPH) simulations of collisions between bodies of different compositions, including those that are water rich. The accuracy of these relations is also comparable to the deviations of results between different SPH codes and initial thermal/rotational conditions. We illustrate the paucity of disruptive collisions between major bodies, as compared to collisions between less massive planetesimals in late-stage planet formation, and thus focus on more probable, low-velocity collisions, though our relations remain relevant to disruptive collisions as well. We also pay particular attention to the transition zone between merging collisions and those where the impactor does not merge with the target, but continues downrange, a "hit-and-run" collision. We find that hit-and-run collisions likely occur more often in density-stratified bodies and across a wider range of impact angles than suggested by the most commonly used analytic approximation. We also identify a possible transitional zone in gravity-dominated collisions where larger bodies may undergo more disruptive collisions when the impact velocity exceeds the sound speed, though understanding this transition warrants further study. Our results are contrary to the commonly assumed invariance of total mass (scale), density structure, and material composition on the largest remnants of giant impacts. We provide an algorithm for adopting our model into N-body planet formation simulations, so that the mass of growing planets and debris can be tracked.


A 5-year study of attachment loss and tooth loss in community-dwelling older adults.
Tooth loss is a widely recognized endpoint measure for the effects of periodontal diseases and the impact of periodontal therapy. In fact, traditional clinical measures of periodontal status often are considered to be surrogate endpoints in that they are assumed to be related to tooth loss. However, the strength of the relationship between attachment loss and tooth loss in a representative population of untreated subjects has not been studied extensively. The purpose of this paper is to present the trends in attachment loss over a 5-yr period in a population of community-dwelling elderly blacks and whites. Specifically, this paper presents attachment loss trends both at the person and tooth level to address the following issues; 1) whether teeth that experience attachment loss during 1 time period are more likely to be lost at the next time period; and 2) given similar levels of attachment loss, why are some people more likely to lose teeth? In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-country area who were examined again at 18, 36 and 60 months. Our findings indicated that teeth with poorer attachment level at baseline had a higher probability of being lost during the next 5 yr and teeth that experienced attachment loss during a time period were more likely to be lost during the next time period than teeth without additional attachment loss. In addition, it appears that there are person-level characteristics associated with increasing tendency towards tooth loss in people with similar periodontal status, a finding that may clarify the relationship between attachment loss and tooth loss.


Arrangement of sympathetic fibers within the human common peroneal nerve: implications for microneurography.
Recently, interest has grown in the firing patterns of individual or multiunit action potential firing patterns in human muscle sympathetic nerve recordings using microneurography. Little is known, however, about sympathetic fiber distribution in human lower limb nerves that will affect the multiunit recordings. Therefore, the purpose of this study was to examine the sympathetic fiber distribution within the human common peroneal nerve using immunohistochemical techniques (tyrosine hydroxylase, avidin-biotin complex technique). Five-micrometer transverse and 10-μm longitudinal sections, fixed in formaldehyde, were obtained from the peroneal nerve that had been harvested from three human cadavers (83 ± 11 yr) within 24 h of death. Samples of rat adrenal gland and brain served as controls. Sympathetic fiber arrangement varied between left and right nerves of the same donor, and between donors. However, in general, sympathetic fibers were dispersed throughout ∼25-38 fascicles of the peroneal nerve. The fibers were grouped in bundles of ∼2-44 axons or expressed individually throughout the fascicles, and the distribution was skewed toward smaller bundles with median and interquartile ratio values of 5 and 1 axons/bundle, respectively. These findings confirm the bundled organization of sympathetic axons within the peroneal nerve and provide the anatomical basis for outcomes in microneurographic studies.


Safety and immunogenicity of heterologous prime-boost immunization with viral-vectored malaria vaccines adjuvanted with Matrix-M™.
The use of viral vectors in heterologous prime-boost regimens to induce potent T cell responses in addition to humoral immunity is a promising vaccination strategy in the fight against malaria. We conducted an open-label, first-in-human, controlled Phase I study evaluating the safety and immunogenicity of Matrix-M adjuvanted vaccination with a chimpanzee adenovirus serotype 63 (ChAd63) prime followed by a modified vaccinia Ankara (MVA) boost eight weeks later, both encoding the malaria ME-TRAP antigenic sequence (a multiple epitope string fused to thrombospondin-related adhesion protein). Twenty-two healthy adults were vaccinated intramuscularly with either ChAd63-MVA ME-TRAP alone (n=6) or adjuvanted with 25μg (n=8) or 50μg (n=8) Matrix-M. Vaccinations appeared to be safe and generally well tolerated, with the majority of local and systemic adverse events being mild in nature. The addition of Matrix-M to the vaccine did not increase local reactogenicity; however, systemic adverse events were reported more frequently by volunteers who received adjuvanted vaccine in comparison to the control group. T cell ELISpot responses peaked at 7-days post boost vaccination with MVA ME-TRAP in all three groups. TRAP-specific IgG responses were highest at 28-days post boost with MVA ME-TRAP in all three groups. There were no differences in cellular and humoral immunogenicity at any of the time points between the control group and the adjuvanted groups. We demonstrate that Matrix-M can be safely used in combination with ChAd63-MVA ME-TRAP heterologous prime-boost immunization without any reduction in cellular or humoral immunogenicity. Clinical Trials Registration NCT01669512.


Molecular cloning of DNA complementary to Drosophila melanogaster alpha-amylase mRNA.
Several lambda clones containing cDNAs from Drosophila melanogaster were identified in a lambda cDNA bank using two different approaches: (i) cross-species hybridization using a mouse amylase cDNA probe, and (ii) probing with a differential probe, generated from Drosophila RNA. An amylase cDNA fragment was used, in turn, for the isolation and characterization of amylase genomic clones. The size of the Drosophila amylase mRNA was estimated at 1650 b. This is comparable with the size of the murine amylase messenger that encodes a protein of similar molecular weight. In Drosophila larvae, amylase mRNA can account for as little as 0.01% of the poly(A)+ RNA under conditions of dietary glucose repression or greater than 1% of poly(A)+ RNA under derepressing dietary conditions.


LITAF Promotes Atherosclerotic Plaque Formation by Stimulating the NF-κB Inflammatory Pathway.
Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) protein is a newly discovered inflammatory protein. This study aims to study the role of LITAF in the formation of atherosclerosis. A total of 10 C57BL/6J mice and 10 C57BL/6J mice with knockout of LITAF gene (C57BL/6J-LITAF-) were divided into two groups: the control group and the LITAF-/- group. The animals were accommodated for 16 weeks and then euthanized with their hearts and aortas isolated thereafter. Next, the roots of the mouse aorta were cryosectioned and stained with Oil Red O staining and immunohistochemical staining (CD68, α-SMA, and Masson), respectively. The area of Oil Red O staining and the proportion of positive expression after immunohistochemical staining were then compared between the control and LITAF-/- groups. At the same time, the blood of mice was collected for the extraction of proteins and RNA. The proteins and RNA were used to detect the expression of major molecules of the NF-κB inflammatory pathway in mice in the control group and the LITAF-/- group by Western blotting and RT-PCR. Oil Red O staining of the aortic root sections of the mice in each group revealed that the area of atherosclerotic plaques in the LITAF-/- group was substantially lower than that in the control group (P<0.05). Moreover, immunohistochemical staining determined that the expression level of α-SMA and CD68 in the LITAF-/- group was significantly lower than that in the control group, whereas the results were reversed following Masson staining (P<0.05). The expression levels of P65 and caspase 3 were significantly lower in the LITAF-/- group than in the control group (P<0.05), whereas the expression level of IκB was higher in the LITAF-/- group. LITAF might participate in the formation of atherosclerotic plaque through the NF-κB pathway and play a promoting role in the formation of atherosclerosis.


Allosteric regulation of phosphonoacetaldehyde hydrolase by n-butylphosphonic acid.
The effect of n-butylphosphonic acid on the activity of phosphonoacetaldehyde hydrolase from Pseudomonas aeruginosa was investigated: at low concentrations this compound appeared as an activator of the enzyme activity, whereas at higher concentrations it exhibited inhibitory properties. The experimental results were modelled according to an allosteric model involving two different classes of sites for n-butylphosphonic acid.


A new generalizable test for detection of mutations affecting Tn10 transposition.
We describe here a new rapid screen that allows easy detection of transposon or host mutations that affect Tn10 transposition in Escherichia coli. This test involves a new Tn10 derivative called the "mini-lacZ-kanR fusion hopper" or mini-Tn10-LK for short. This element does not direct expression of beta-galactosidase when present at its original starting location on a suitably engineered plasmid or phage genome because it lacks appropriate transcription and translation start signals. However, transposition of this element into the chromosome of E. coli lacZ- bacteria leads to productive fusions in which the lacZ gene within the transposon is expressed from external chromosomal signals. Such fusions are readily detectable on MacConkey lactose indicator plates as red (Lac+) papillae inside of white (LacZ-) colonies. The length of time required to see red papillae appearing in a white colony sensitively and accurately reflects the transposition frequency of the mini-transposon within the colonies. Differences in times for color formation are sensitive enough that 10-fold differences in transposition frequency can readily be detected. This papillation assay can be used to identify mutant clones in which the frequency of Tn10 transposition is either increased or decreased. We have successfully used the assay to identify mutations in the terminal sequences of Tn10; mutations in the Tn10 transposase gene or the bacterial host can be isolated just as easily. This screen should be readily adaptable to transposable elements other than Tn10.


Thermoregulatory consequences of long-term microwave exposure at controlled ambient temperatures.
This study was designed to identify and measure changes in thermoregulatory responses, both behavioral and physiological, that may occur when squirrel monkeys are exposed to 2450-MHz continuous wave microwaves 40 hr/week for 15 weeks. Power densities of 1 or 5 mW/cm2 (specific absorption rate = 0.16 W/kg per mW/cm2) were presented at controlled environmental temperatures of 25, 30, or 35 degrees C. Standardized tests, conducted periodically, before, during, and after treatment, assessed changes in thermoregulatory responses. Dependent variables that were measured included body mass, certain blood properties, metabolic heat production, sweating, skin temperatures, deep body temperature, and behavioral responses by which the monkeys selected a preferred environmental temperature. Results showed no reliable alteration of metabolic rate, internal body temperature, blood indices, or thermoregulatory behavior by microwave exposure, although the ambient temperature prevailing during chronic exposure could exert an effect. An increase in sweating rate occurred in the 35 degrees C environment, but sweating was not reliably enhanced by microwave exposure. Skin temperature, reflecting vasomotor state, was reliably influenced by both ambient temperature and microwaves. The most robust consequence of microwave exposure was a reduction in body mass, which appeared to be a function of microwave power density.


Telomerase activity in normal adult Brown Norway rat seminal vesicle: regional distribution and age-dependent changes.
Telomerase activity is essential for protection of cells against the telomere erosion that occurs with each round of cell replication, and thus appears to play a role in the indefinite replication potential of some, but not all, eukaryotic cells. In this regard, some tissues contain stem cells that have a long proliferative life-span and are capable of regenerating or renewing the somatic epithelial cell population within the tissue. Because the adult seminal vesicle exhibits the ability to regenerate during androgen-replacement after castration, we hypothesized that a pool of cells with regenerating potential is present in the adult seminal vesicle, which expresses telomerase activity. In this study, we used a highly sensitive PCR-based telomerase assay [the telomeric repeat amplification protocol (TRAP) assay] to detect telomerase activity in rat seminal vesicle. Our results show that telomerase activity is, indeed, present in the normal adult rat seminal vesicle, but that, in the presence of seminal vesicle fluid, telomerase activity cannot be detected. In fact, seminal vesicle fluid was found to contain some factor(s) that is inhibitory for the TRAP assay. In addition, we found that telomerase activity in the seminal vesicle changes with age and is regionally distributed within the distal, intermediate, and proximal segments of the duct. These results suggest that as is the case for the rat prostate, a population of telomerase-positive cells is present within the adult rat seminal vesicle, and thereby, this organ retains throughout life the potential to regenerate in response to androgen replacement following castration-induced apoptotic cell death.


New Insight into the Mechanism of the Hydrogen Evolution Reaction on MoP(001) from First Principles.
Molybdenum phosphide-based catalysts have recently exhibited excellent catalytic activities for the hydrogen evolution reaction (HER) in wide pH range conditions; the intrinsic reaction mechanism, on the other hand, has not been well established. Herein, by employing the MoP as the prototypical molybdenum phosphide-based catalyst, HER activities in both acid and neutral conditions were studied by conducting periodic density functional theory calculations. Thermodynamic analysis of hydrogen atoms absorbed on both P- and Mo-terminated surfaces were compared, as well as all the reaction energy and activation energy barriers for reactions involved in the HER process. Calculation results revealed that, in an acid condition, the Volmer-Heyrovsky and Volmer-Tafel reaction mechanisms were dominated on the P-terminated and Mo-terminated catalyst surfaces, where Heyrovsky and Volmer reactions were the rate-determining step, respectively. Additionally, water splitting was introduced to the current reaction mechanism and a small reaction activation energy barrier was revealed on the P-terminated surface. Besides, a relevant small activation energy was obtained in the Tafel reaction on the defect of the P-terminated surface in a neutral solution. Theoretical results proved that HER could take place readily on both P- and Mo-terminated catalyst surfaces via different reaction mechanisms in the acid condition from the view of atom scale. More important, computational results uncovered that HER could also occur on the P-terminated surface with the assistance of surface defect in the neutral condition, which sheds new light on the HER mechanism on transition metal phosphite-based catalysts. The doping effect on HER activity was further investigated in theory and calculation results, indicating that catalytic performance could be improved by substitutional doping of the Mo atom with metals such as Mn and W.


Comparison of oxidation products from DNA components by gamma-irradiation and Fenton-type reactions.
The four 2'-deoxyribonucleosides were gamma-irradiated or were aerobically treated with Fenton-type-reagents, Fe(II)-EDTA or a renal carcinogen Fe(II)-nitrilotriacetic acid (NTA) under the neutral conditions. The reaction mixtures were immediately analyzed by reverse-phase HPLC. Major products detected were 2-hydroxydeoxyadenosine (2-OH-dA), 8,5'-cyclodeoxyadenosine (cyclo-dA), 8-hydroxydeoxyadenosine (8-OH-dA). 5-formyldeoxyuridine (5-CHO-dU), 5-hydroxydeoxycytidine (5-OH-dC), 8-hydroxydeoxyguanosine (8-OH-dG), 8,5'-cyclodeoxyguanosine (cyclo-dG), and glyoxal and its adduct with dG. Ratio of these oxidized products were dramatically changed depending upon the agents used. For example, 2-OH-dA was a modified nucleoside produced most efficiently by Fe(II)-EDTA, while 5-CHO-dU and 5-OH-dC were the major products by the Fe(II)-NTA treatment and gamma-irradiation, respectively. Glyoxal itself was estimated to be produced most frequently (13 folds of 8-OH-dG) when treated with Fe(II)-EDTA, but its formation was not detected by the treatment with Fe(II)-NTA or by gamma-irradiation. 8-OH-dA was not produced by Fe-EDTA or Fe-NTA but was produced by gamma-irradiation. In contrast, 2-OH-dA was not produced by gamma-irradiation. These results suggest that triphosphates of 2-OH-dA, cyclo-dA, 8-OH-dA, cyclo-dG, 5-CHO-dU, 5-OH-dC, and glyoxal-dG as well as 8-OH-dG may be produced in cells with different ratio by various types of oxidative stress and involved in mutagenesis and carcinogenesis.


[Consensus on physical health of patients with schizophrenia from the Spanish Societies of Psychiatry and Biological Psychiatry].
Schizophrenia has traditionally been associated with higher rates of physical comorbidity and excess mortality. To develop a Spanish consensus document concerning the physical health of patients with schizophrenia and the interventions required to reduce the over-morbidity and over-mortality of these patients. Method. The process consisted of: a) systematic review of the literature in the Medline database up to January 2006 and manual review of the bibliographical references of the papers obtained; b) reviews of national and international guides by the coordinating committee and medical specialist acting as expert advisors; c) multidisciplinary consensus meetings, and d) editing of the final consensus document. Compared to the general population, patients with schizophrenia present higher rates of infection (HBV, HCV, HIV), endocrine/metabolic disorders, cardiac and respiratory diseases (over-morbidity) and higher global death risk, as well as death from natural causes--basically respiratory, cardiovascular and oncological diseases (over-mortality). As a guide, therefore, this document proposes a series of interventions to be performed by psychiatrists to reduce the current rates. Given the over-morbidity and overmortality of patients with schizophrenia, awareness of these aspects should be increased among primary healthcare providers and specialists, including psychiatrists, and physical health problems should be incorporated into psycho-educational programs, and treatment compliance and severe mental disorder treatment units.


Inhibition of morphine tolerance by NMDA receptor antagonists in the formalin test.
5-Nitro-6,7-dimethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1328) was characterized in vitro for antagonism of excitatory amino acid receptors, and subsequently tested in vivo and compared with MK-801 for phencyclidine (PCP)-like motor stimulation, antinociception, and effects on morphine tolerance in mice. Assayed on rat cerebral cortical glutamate receptors expressed in Xenopus oocytes ACEA-1328 showed potent (Kb approximately 40 nM) antagonism at NMDA receptor/glycine sites and moderate (Kb approximately 3 microM) antagonism at non-NMDA receptors. In both cases inhibition was predominantly competitive. ACEA-1328 was weak, or inactive, at NMDA receptor glutamate recognition sites, metabotropic receptors and opioid binding sites. In the formalin and rotarod tests ACEA-1328 and MK-801 produced both antinociception and disturbances of motor coordination. MK-801 caused a PCP-like motor stimulatory effect, whereas ACEA-1328 was devoid of such an effect. In tolerance studies, ACEA-1328 and MK-801 each blocked morphine tolerance in the formalin test, the effect of ACEA-1328 was dose-dependent. Our data contribute to a growing body of evidence which suggests that activation of NMDA receptors is critical for the development of opioid tolerance, and that antagonism at NMDA receptor/glycine sites may have potential as a means of diminishing tolerance with no PCP-like motor stimulatory side effects.


Dietary omega-3 fatty acid deficiency and visual loss in infant rhesus monkeys.
Linolenic acid (18:3 omega 3) is a dietary precursor of docosahexaenoic acid (22:6 omega 3), the major fatty acid in the photoreceptor membranes of the retina. We hypothesized that rhesus monkeys deprived of dietary omega-3 fatty acids during prenatal and postnatal development would show plasma depletion of these fatty acids and visual impairment. Semipurified diets low in omega-3 fatty acids were fed to one group of adult female rhesus monkeys throughout pregnancy and to their infants from birth. A control group of mothers and infants received similar diets but supplying ample linolenic acid. In the plasma phospholipids of deficient infants, linolenic acid was generally undetectable and 22:6 omega 3 levels became progressively depleted, falling from 42% of control values at birth to 21% at 4 wk, 9% at 8 wk, and 6% at 12 wk of age. In the other plasma lipid classes, 22:6 omega 3 was undetectable by 12 wk. The visual acuity of the deprived infants, as measured by the preferential looking method, was reduced by one-fourth at 4 wk (P less than 0.05) and by one-half at 8 and 12 wk (P less than 0.0005) compared with control infants. These results suggest that omega-3 fatty acids may be an essential nutrient, and that 22:6 omega 3 may have a specific function in the photoreceptor membranes of the retina.


Drug-induced sleep endoscopy improves intervention efficacy among patients treated for obstructive sleep apnea with a mandibular advancement device.
To compare the short-term treatment effect of a mandibular advancement device (MAD) with and without previous drug-induced sleep endoscopy (DISE) on polysomnography (PSG) and other sleep apnea-related treatment outcomes (Short Form Health Survey [SF-36] and Epworth Sleepiness Scale [ESS]) among adults with mild, moderate, and severe obstructive sleep apnea (OSA). We hypothesized that using DISE would improve the efficacy of MADs on the sleep apnea parameters. The study sample consisted of patients with OSA who were unable or unwilling to tolerate a CPAP device, divided into an experimental (with DISE) and a control (without DISE) group. Of 50 patients with OSA, 40 men (80%), mean age was 48.8 ± 12,3 years. The mean apnea-hypopnea index (AHI) score of both groups decreased significantly between baseline and the 8-week follow-up titration PSG with MAD in situ, from 31.7 ± 17.3 (mean ± SD) apnea-hypopnea episodes/h to 7.0 ± 6.4/h (p < 0.0001) in the experimental group, and from 22.5 ± 16.6 episodes/h to 11.4 ± 8.0/h (p < 0.024) in the control group. Capillary oxygen saturation (SpO2) levels did not change significantly between the two timepoints for either group. The SF-36 (p < 0.023) and ESS (p < 0.036) results of both groups improved significantly between baseline and the 8-week follow-up after starting MAD treatment; however, the improvement in quality of life was significantly more pronounced in the experimental group than in the control group (p < 0.0001). DISE provides a significant benefit to patients with OSA undergoing MAD treatment. It can be used as a valuable prediction tool in clinical practice for the management of patients with OSA, even those with moderate and severe disease.


DNA-dependent protein kinase interacts with antigen receptor response element binding proteins NF90 and NF45.
The DNA-dependent protein kinase (DNA-PK) is composed of a large catalytic subunit of approximately 470 kDa (DNA-PKcs) and the DNA-binding protein, Ku. Absence of DNA-PK activity confers sensitivity to x-rays and defects in both DNA double-strand break repair and V(D)J recombination. However the precise function of DNA-PK in DNA double-strand break repair is not known. Here we show, using electrophoretic mobility shift assays, that polypeptides in a fraction purified from human cells interact with DNA-PK and stabilize the formation of a complex containing DNA-PKcs-Ku and DNA. Five polypeptides in this fraction have been identified by amino-terminal sequence analysis and/or immunoblotting. These proteins are NF90 and NF45, which are the 90- and 45-kDa subunits of a protein known to bind specifically to the antigen receptor response element of the interleukin 2 promoter, and the alpha, beta, and gamma subunits of eukaryotic translation initiation factor eIF-2. We also show that NF90, NF45, and eIF-2 beta are substrates for DNA-PK in vitro. In addition, recombinant NF90 promotes formation of a complex between DNA-PKcs, Ku, and DNA, and antibodies to recombinant NF90 or recombinant NF45 immunoprecipitate DNA-PKcs in vitro. Together, our data suggest that NF90, in complex with NF45, interacts with DNA-PKcs and Ku on DNA and that NF90 and NF45 may be important for the function of DNA-PK.


The effect of temperature on sulfur and oxygen isotope fractionation by sulfate reducing bacteria (Desulfococcus multivorans).
Temperature influences microbiological growth and catabolic rates. Between 15 and 35 °C the growth rate and cell specific sulfate reduction rate of the sulfate reducing bacterium Desulfococcus multivorans increased with temperature. Sulfur isotope fractionation during sulfate reduction decreased with increasing temperature from 27.2 ‰ at 15 °C to 18.8 ‰ at 35 °C which is consistent with a decreasing reversibility of the metabolic pathway as the catabolic rate increases. Oxygen isotope fractionation, in contrast, decreased between 15 and 25 °C and then increased again between 25 and 35 °C, suggesting increasing reversibility in the first steps of the sulfate reducing pathway at higher temperatures. This points to a decoupling in the reversibility of sulfate reduction between the steps from the uptake of sulfate into the cell to the formation of sulfite, relative to the whole pathway from sulfate to sulfide. This observation is consistent with observations of increasing sulfur isotope fractionation when sulfate reducing bacteria are living near their upper temperature limit. The oxygen isotope decoupling may be a first signal of changing physiology as the bacteria cope with higher temperatures.


Examination of selection criteria for a program in occupational therapy.
The purpose of this study was to determine if the results of preselection interviews in combination with preselection academic performance offer better predictions of academic performance in occupational therapy than either of these criteria taken singly. The sample consisted of 48 high school students and 31 university students admitted to the program in occupational therapy at the University of Western Ontario from 1978 to 1980. The results indicated that for university students, previous academic performance alone was the best predictor for their performance in first-year occupational therapy. For high school students, the combination of 5 of the 12 interview items with previous academic performance produced the best predictor of successful academic performance in occupational therapy. This implies that for high school students at least, the interview and previous academic performance should both be considered as important selection criteria.


Central pulmonary artery lesions in chronic obstructive pulmonary disease: A transesophageal echocardiography study.
In patients with acute pulmonary embolism, transesophageal echocardiography (TEE) often reveals presumably thrombotic lesions within the central pulmonary arteries (CPAs). These CPA lesions, when found in patients with primary pulmonary hypertension, have been attributed to in situ thrombosis or atherosclerosis. We hypothesized that similar CPA lesions may also develop in patients with chronic obstructive pulmonary disease (COPD) in the absence of pulmonary embolism. We examined by TEE 25 patients with COPD and 27 control patients with left heart disease. None of the patients had previous pulmonary embolism or ileofemoral and popliteal vein thrombosis. By use of TEE, CPA lesions were found in 12 COPD patients (48%) and 2 control patients (7.4%) (P<0.01). When CPA lesions were subdivided into types 1 (protruding and mobile) and 2 (wall-adherent), type 1 lesions proved to be uncommon, being found within the pulmonary trunk in 12% and 3.7% of COPD and control patients, respectively (P=NS). Conversely, type 2 lesions, which were always localized in the right pulmonary artery, were frequent in COPD patients (36%) and rare in control patients (3.7%) (P<0.01). When available, helical CT and MR angiography confirmed TEE findings, supporting an atherosclerotic origin of type 2 lesions, which were different from typical thrombotic lesions. FEV(1)/FVC ratio, RV/TLC ratio, PaO(2), hematocrit value, and pulmonary artery systolic pressure were not significantly different in COPD patients with and without CPA lesions. At TEE, however, COPD patients with CPA lesions showed a larger size of the main and right pulmonary arteries. TEE often reveals CPA lesions in stable patients with COPD even in the absence of significant pulmonary hypertension and not in close relation with the severity of pulmonary dysfunction.


A microfluidic device for immuno-affinity-based separation of mitochondria from cell culture.
In this work, we present a method to isolate mitochondria of mammalian cells after cell disruption on microscale. The device is composed of linear microchannels cast in PDMS (polydimethylsiloxane). Specific antibodies against the translocase outer membrane protein of the mitochondria are immobilized on the surface of the substrate using an avidin-biotin sandwich construct. The mitochondria can be captured in the channel, whereas the remains of the cell lysate flow out the chip unhindered. The captured mitochondria can be observed directly on chip. A successful immobilization of pre-isolated mitochondria was shown at a flow rate between 0 and 5 μl min(-1) (≈0-2.5 mm s(-1)). After fluorescence staining, we demonstrated that the mitochondria covered around 3% of the channel surface. The mitochondria appeared in a distinct spherical shape with a diameter of around 0.8-1.2 μm. Further validation of the microfluidic device using non-treated cell lysate was done at 2 μl min(-1). The immobilized mitochondria were smaller with a diameter of around ≈490 nm. We observed a surface coverage of around 4%. The immobilized mitochondria were active and stable for over 2 h without cooling and were shown to be able to produce ATP under stage 3 respiration on chip.