A superconducting thermal switch with ultrahigh impedance for interfacing superconductors to semiconductors.
A number of current approaches to quantum and neuromorphic computing use superconductors as the basis of their platform or as a measurement component, and will need to operate at cryogenic temperatures. Semiconductor systems are typically proposed as a top-level control in these architectures, with low-temperature passive components and intermediary superconducting electronics acting as the direct interface to the lowest-temperature stages. The architectures, therefore, require a low-power superconductor-semiconductor interface, which is not currently available. Here we report a superconducting switch that is capable of translating low-voltage superconducting inputs directly into semiconductor-compatible (above 1,000 mV) outputs at kelvin-scale temperatures (1K or 4 K). To illustrate the capabilities in interfacing superconductors and semiconductors, we use it to drive a light-emitting diode (LED) in a photonic integrated circuit, generating photons at 1K from a low-voltage input and detecting them with an on-chip superconducting single-photon detector. We also characterize our device's timing response (less than 300 ps turn-on, 15 ns turn-off), output impedance (greater than 1MΩ), and energy requirements (0.18fJ/μm2,3.24mV/nW).


A DNA fragment mapped within the submicroscopic deletion of Ph1, a chromosome pairing regulator gene in polyploid wheat.
Bread wheat is an allohexaploid consisting of three genetically related (homoeologous) genomes. The homoeologous chromosomes are capable of pairing but strict homologous pairing is observed at metaphase 1. The diploid-like pairing is regulated predominantly by Ph1, a gene mapped on long arm of chromosome 5B. We report direct evidence that a mutant of the gene (ph1b) arose from a submicroscopic deletion. A probe (XksuS1-5) detects the same missing fragment in two independent mutants ph1b and ph1c and a higher intensity fragment in a duplication of the Ph1 gene. It is likely that XksuS1-5 lies adjacent to Ph1 on the same chromosome fragment that is deleted in ph1b and ph1c. XksuS1-5 can be used to tag Ph1 gene to facilitate incorporation of genetic material from homoeologous genomes of the Triticeae. It may also be a useful marker in cloning Ph1 gene by chromosome walking.


Consistency of traumatic brain injury reporting in older adults with and without cognitive impairment.
Medical history information regarding prior traumatic brain injury (TBI) usually relies on self-report, although little is known about the reliability of this information with regard to injuries sustained years or decades earlier. Even less is known about the reliability of self-reported medical history information in older individuals with cognitive impairment. To this end, we assessed the test-retest reliability of self-reported TBI history in a large, national sample. Participants (n = 4309) were older adults with intact cognition, mild cognitive impairment (MCI) and Alzheimer's disease (AD) from the National Alzheimer's Coordinating Center. Subjects provided TBI history information at baseline and one annual follow-up visit. Consistency of self-reported history of TBI with <5 minutes loss of consciousness (mLOC) and TBI with ≥5 mLOC reported at time 1 and 2 was analyzed across diagnostic groups. Overall, subjects provided reports of TBI history at follow-up that were highly consistent with baseline reports (97.8-99.6% agreement), and Cohen's kappa coefficients were all larger than .80 and statistically significant, maximum p < .001. Furthermore, level of cognitive impairment was not a significant predictor of consistency in reporting. These data are some of the first to suggest that self-report may be a consistent method of obtaining remote TBI history in the absence of medical records for older individuals, regardless of cognitive impairment.


[Plastic repair of oral and pharyngeal defects after extensive operations].
The report deals with reconstruction for defects in posterior areas of the mouth and stomatopharynx caused by extensive surgery. A myocutaneous sternomastoid flap was formed with due account of nutrient arterial trunks branching off from occipital and superior thyroid arteries thus promoting wound healing and preventing necrosis. The procedure was performed in 16 cases; in 12 of them, it was performed simultaneously with the removal of primary tumor and radical surgery on the neck.


Characterisation and application of antibodies specific for the long platelet-derived growth factor A and B chains.
The platelet-derived growth factor (PDGF) family comprises important mitogens for mesenchymal cells. The active dimeric form of PDGF consists of four structurally related A, B, C, and D chains. All PDGF-variants bind to PDGF-receptors. The A and B chains occur with and without basic C-terminal amino acid extensions as long (A(L) and B(L)) and short (A(S) and B(S)) isoforms. PDGF-A and -B form homo- or heterodimers. The biological relevance of short and long isoforms is unknown, although it may relate to different affinities for glycosaminoglycans of the cell glycocalix and intercellular matrix. Commercially available anti-PDGF-A and anti-PDGF-B antibodies cannot discriminate between the short and the long isoforms. Thus, to investigate the function of the long and short isoforms, we raised antibodies specific for the long A and B chain isoforms. The antibodies were affinity-purified and their properties analysed by surface plasmon resonance. Inhibition studies with different PDGF homodimers and dot-blot studies proved their high specificity for the respective isoforms. Both antibodies recognised the target PDGF homodimers complexed to the glycocalix of human arterial smooth muscle cells and human monocyte-derived macrophages. By using these specific antibodies, we were able to confirm at the protein level the synthesis of PDGF-A and -B during differentiation of human monocyte-derived macrophages and to demonstrate the presence of the PDGF-A(L) and PDGF-B(L) isoforms in human arterial tissue.


Redox pathways in DNA oxidation: kinetic studies of guanine and sugar oxidation by para-substituted derivatives of oxoruthenium(IV).
The oxidation of nucleotides and DNA by a series of complexes based on Ru(tpy)(bpy)O2+ (1) was investigated (tpy = 2,2':6',2"-terpyridine; bpy = 2,2'-bipyridine). These complexes were substituted with electron-donating or-withdrawing substituents in the para positions of the polypyridyl ligands so that the oxidation potentials of the complexes were affected but the reaction trajectory of the oxo ligand with DNA was the same throughout the series. The prepared complexes were (with E1/2(III/II) and E1/2(IV/III) values in volts versus Ag/AgCl) Ru(4'-EtO-tpy)(bpy)O2+ (2; 0.47, 0.60), Ru(4'-Cl-tpy)(bpy)O2+ (3; 0.55, 0.63), Ru(tpy)(4,4'-Me2-bpy)O2+ (4; 0.48, 0.62), and Ru(tpy)(4,4'-Cl2-bpy)O2+ (5; 0.58, 0.63). The complexes oxidized deoxycytosine 5'-monophosphate at the sugar moiety (k = 0.24-0.47 M-1 s-1) and guanosine 5'-monophosphate at the base moiety (k = 6.1-15 M-1 s-1). The rate constants increase across these ranges in the order 3 > 1 > 4 > 2, which is the same order as the redox potentials of the complexes. The effect of the base on these reactions was also studied, and xanthine was found to react with 1 much faster than guanine while hypoxanthine was less reactive than the sugar moiety. The complexes all oxidized oligonucleotides to generate base-labile lesions at guanine and a combination of spontaneous and base-labile scission at the sugar functionalities. The selectivity of cleavage in duplex and single-stranded DNA was not a strong function of the substituents on the metal complex.


The effect of depth of dentin demineralization on bond strengths and morphology of the hybrid layer.
Previous studies have shown that different phosphoric acid-based etchants do not penetrate intertubular dentin to the same depth. The purpose of this study was to determine the effect of different phosphoric acid-based conditioners on dentin shear bond strengths of three one-bottle bonding systems and to evaluate the corresponding interfacial ultramorphology. The null hypothesis to be tested was that no correlation could be established between the depth of intertubular demineralization and dentin shear bond strengths. The labial surface of 90 bovine incisors was polished to expose middle dentin. The specimens were randomly assigned to three one-bottle adhesive systems (n = 30): OptiBond SOLO, Permaquick PQ1, and Single Bond. For each adhesive system the specimens were divided into three subgroups of different silica-thickened etching gels (n = 10): 37.5% phosphoric acid gel (Kerr Gel Etchant), 35% phosphoric acid gel (Ultraetch), and 35% phosphoric acid gel (Scotchbond Etching Gel). After 24 hours in water at 37 degrees C, the specimens were thermocycled for 500 cycles in baths kept at 5 degrees C and 55 degrees C and the shear bond strengths measured. The data were analyzed with one-way and two-way ANOVA. Further, the adhesives were applied to 800 microns-thick bovine dentin disks (two per subgroup), which were restored with a low-viscosity composite resin. Six small dentin/resin sticks with a cross-section of 1.0 mm x 1.0 mm were obtained from each bonded disk. They were then decalcified in a buffered solution of EDTA, fixed, stained, and sectioned in 90 nanometer-thick slices to observe under the Transmission Electron Microscope (TEM). The mean shear bond strengths were not statistically different at a confidence level of 95%. When the means were pooled for dentin adhesive and for etching gel, the number of cohesive failures was greater for Permaquick PQ1 and for Ultraetch, respectively. Pearson's correlation coefficient showed no correlation between hybrid layer thickness and bond strengths. The ultramorphological observation showed that all materials penetrated the dentin and formed a hybrid layer, regardless of the etching gel used.


Detection of the Peanut Allergens Ara h 2 and Ara h 6 in Human Breast Milk: Development of 2 Sensitive and Specific Sandwich ELISA Assays.
Little is known about breast milk as a vehicle for tolerance development or sensitization to peanuts very early in life. Thus, well-characterized and highly sensitive detection systems for the reliable determination of peanut allergens in breast milk are mandatory. For the quantification of the marker allergens Ara h 2 and Ara h 6 in the low nanogram per milliliter range in breast milk samples of a German cohort, sensitive and highly specific sandwich ELISAs were optimized and validated. The Ara h 2 ELISA revealed a limit of detection (LOD) of 1.3 ng Ara h 2/mL and a quantification range of 2.3-250 ng/mL, the Ara h 6 ELISA showed an LOD of 0.7 ng/mL and a working range of 1.1-14.4 ng/mL. The assays showed no relevant cross-reactivity against other potentially cross-reactive legume, seed, and tree nut extracts (<0.01%, except for Ara h 1 in the Ara h 2 ELISA <0.1%). Ara h 2 was detectable in breast milk samples from 14/40 (35%) of the participants in concentrations from 2.3 to 184 ng/mL, Ara h 6 appeared in 9/40 (22.5%) of the lactating mothers between 1.1 and 9.7 ng/mL, and 1 highly positive sample with 79 ng/mL. Both allergens appeared at the same time points, but Ara h 6 in lower concentrations than Ara h 2. Sensitive and specific diagnostic tools for the determination of Ara h 2 and Ara h 6 in human breast milk were established. The kinetics of secreted Ara h 2 and Ara h 6 seem to be similar but with a difference in concentration. Follow-up investigations on their tolerogenic or sensitizing properties in breast milk become now accessible.


Flower diversity and bee reproduction in an arid ecosystem.
Diverse flower communities are more stable in floral resource production along the flowering season, but the question about how the diversity and stability of resources affect pollinator reproduction remains open. High plant diversity could favor short foraging trips, which in turn would enhance bee fitness. In addition to plant diversity, greater temporal stability of floral resources in diverse communities could favor pollinator fitness because such communities are likely to occupy the phenological space more broadly, increasing floral availability for pollinators throughout the season. In addition, this potential effect of flower diversity on bee reproduction could be stronger for generalist pollinators because they can use a broader floral spectrum. Based on above arguments we predicted that pollinator reproduction would be positively correlated to flower diversity, and to temporal stability in flower production, and that this relationship would be stronger for the most generalized pollinator species. Using structural equation models, we evaluated the effect of these variables and other ecological factors on three estimates of bee reproduction (average number of brood cells per nest per site, total number of brood cells per site, and total number of nests per site), and whether such effects were modulated by bee generalization on floral resources. Contrary to our expectations, flower diversity had no effect on bee reproduction, stability in flower production had a weakly negative effect on one of the bee reproductive variables, and the strength of the fitness-diversity relationship was unrelated to bee generalization. In contrast, elevation had a negative effect on bee reproduction, despite the narrow elevation range encompassed by our sites. Flower diversity did not affect the reproduction of the solitary bees studied here. This result could stem from the context dependence of the diversity-stability relationship, given that elevation had a positive effect on flower diversity but a negative effect on bee reproduction. Although high temporal stability in flower production is expected to enhance pollinator reproduction, in our study it had a weakly negative-instead of positive-effect on the average number of brood cells per nest. Other environmental factors that vary with elevation could influence bee reproduction. Our study focused on a small group of closely-related bee species, which cautions against generalization of our findings to other groups of pollinators. More studies are clearly needed to assess the extent to which pollinator demography is influenced by the diversity of floral resources.


Two-level corpectomy versus three-level discectomy for cervical spondylotic myelopathy: a comparison of perioperative, radiographic, and clinical outcomes.
In the treatment of cervical spondylotic myelopathy (CSM), anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) are effective decompressive techniques. It remains to be determined whether ACCF and ACDF offer equivalent outcomes for multilevel CSM. In this study, the authors compared perioperative, radiographic, and clinical outcomes between 2-level ACCF and 3-level ACDF. Between 2006 and 2012, all patients at the authors' hospital who underwent 2-level ACCF or 3-level ACDF performed by 1 of 2 surgeons were identified. Primary outcomes of interest were sagittal Cobb angle, adjacent-segment disease (ASD) requiring surgery, neck pain measured by visual analog scale (VAS), and Nurick score. Secondary outcomes of interest included estimated blood loss (EBL), length of stay, perioperative complications, and radiographic pseudarthrosis rate. Chi-square tests and 2-tailed Student t-tests were used to compare the 2 groups. A subgroup analysis of patients without posterior spinal fusion (PSF) was also performed. Twenty patients underwent 2-level ACCF, and 35 patients underwent 3-level ACDF during a 6-year period. Preoperative Nurick scores were higher in the ACCF group (2.1 vs 1.1, p = 0.014), and more patients underwent PSF in the 2-level ACCF group compared with patients in the 3-level ACDF group (60.0% vs 17.1%, p = 0.001). Otherwise there were no significant differences in demographics, comorbidities, and baseline clinical parameters between the 2 groups. Two-level ACCF was associated with significantly higher EBL compared with 3-level ACDF for the anterior stage of surgery (382.2 ml vs 117.9 ml, p < 0.001). Two-level ACCF was also associated with a longer hospital stay compared with 3-level ACDF (7.2 days vs 4.9 days, p = 0.048), but a subgroup comparison of patients without PSF showed no significant difference in length of stay (3.1 days vs 4.4 days for 2-level ACCF vs 3-level ACDF, respectively; p = 0.267). Similarly, there was a trend toward more complications in the 2-level ACCF group (20.0%) than the 3-level ACDF group (5.7%; p = 0.102), but a subgroup analysis that excluded those who had second-stage PSF no longer showed the same trend (2-level ACCF, 0.0% vs 3-level ACDF, 3.4%; p = 0.594). There were no significant differences between the ACCF group and the ACDF group in terms of postoperative sagittal Cobb angle (7.2° vs 12.1°, p = 0.173), operative ASD (6.3% vs 3.6%, p = 0.682), and radiographic pseudarthrosis rate (6.3% vs 7.1%, p = 0.909). Both groups had similar improvement in mean VAS neck pain scores (3.4 vs 3.2 for ACCF vs ACDF, respectively; p = 0.860) and Nurick scores (0.8 vs 0.7, p = 0.925). Two-level ACCF was associated with greater EBL and longer hospital stays when patients underwent a second-stage PSF. However, the length of stay was similar when patients underwent anterior-only decompression with either 2-level ACCF or 3-level ACDF. Furthermore, perioperative complication rates were similar in the 2 groups when patients underwent anterior decompression without PSF. Both groups obtained similar postoperative cervical lordosis, operative ASD rates, radiographic pseudarthrosis rates, neurological improvement, and pain relief.


Primary hyperparathyroidism and coexisting hyperthyroidism--review of the literature.
Concomitance of hyperthyroidism and hyperparathyroidism is rare and only forty-nine well documented cases could be found in the literature. In the present study, only forty-three patients with adequate available clinical and laboratory data are reported. Hypercalcemia was found in all the patients and five of them (12%) had acute hyperparathyroidism. Two patients were also pregnant and had pancreatitis. Hypercalcuria was found in 73% and hypophosphatemia in 55% of the patients. Eleven patients (26%) had renal concretions. Skeletal roentgenograms showed abnormalities in 63% of the patients. Elevated serum level of alkaline phosphatase was present in 64% of the patients. However, there seemed to be no correlation with the severity of the skeletal lesions. Thyrotoxicosis commenced before that of Hyperparathyroidism in twenty-three patients (53%) whereas in the remaining twenty patients it was impossible to determine which disease began first. The etiologies of hyperparathyroidism as well as the differential diagnosis of parathyroid-related and nonparathyroid-related hypercalcemia are discussed. Microscopically, 74% of the patients had a single adenoma; 16% had hyperplasia of one to three parathyroid glands. One patient had an adenoma in combination with hyperplasia of one parathyroid gland, one had an adenoma and three hyperplastic glands, one had adenomas of two parathyroid glands in combination with hyperplasia of one parathyroid gland, and the other one had carcinoma of a parathyroid gland.2+ Finally, if a thyrotoxic patient still has hypercalcemia when becoming euthyroid after antithyroid therapy, coexisting hyperthyroidism should be considered and an operation should be performed as surgical treatment cured both diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


The science of sustaining health behavior change: the health maintenance consortium.
To enhance understanding of the long-term maintenance of behavior change, as well as effective strategies for achieving sustainable health promotion and disease prevention through the Health Maintenance Consortium (HMC). This introductory research synthesis prepared by the resource center gives context to this theme issue by providing an overview of the HMC and the articles in this journal. It explores the contributions to our conceptualization of behavior change processes and intervention strategies, the trajectory of effectiveness of behavioral and social interventions, and factors influencing the long-term maintenance of behavioral and social interventions. Future directions for furthering the science of maintaining behavior change and reducing the gaps between research and practice are recommended.


Comparison of Ultrasound, Radiography, and Clinical Investigations in the Diagnosis of Early Rheumatoid Synovitis in Patients with Nonspecific Musculoskeletal Symptoms: A Multicenter Cross-Sectional Study.
BACKGROUND Early diagnosis and treatment of rheumatoid synovitis can reduce the progression of rheumatoid arthritis (RA). However, in the early stages of rheumatoid synovitis, patients may only have non-specific musculoskeletal symptoms, and plain film radiographs may not detect early synovial changes. The aim of this study was to compare the sensitivity and specificity of ultrasound with radiography, and clinical investigations in the detection of rheumatoid synovitis in patients presenting with nonspecific musculoskeletal symptoms. MATERIAL AND METHODS This was a non-randomized, cross-sectional, clinical study that included 189 patients who had nonspecific musculoskeletal symptoms. All patients underwent clinical investigations, postero-anterior and dorsal radiographic imaging, and bilateral grey-scale ultrasound examinations of the third and second metacarpophalangeal (MCP) joints, the third and the second proximal interphalangeal (PIP) joints, the second and the fifth metatarsophalangeal (MTP) joints, and the wrist. RESULTS There was no clear predictive value for detection of early synovitis by clinical investigations alone. Plain film radiography of patients only provided accurate information of joint erosions but less information for synovitis. Grey-scale ultrasound was more effective at detecting early synovitis compared with clinical investigations (p=0.00015; q=4.548) and compared with plain film radiography (p=0.0002; q=4.537), and quantified the synovial changes. The predictive values of plain film radiography and clinical investigations had 0.43 and 0.24 sensitivity and 0 specificity compared with ultrasound. CONCLUSIONS The findings of this study support the use of grey-scale ultrasound in the detection of early rheumatoid synovitis of the fingers and the wrist.


Modification to a testing assembly to enable strain-life measurements in pressurized hydrogen gas.
Strain-controlled fully reversed fatigue testing, or strain-life testing, provides critical information on material lifetime and damage response. Strain-life data in hydrogen gas environments is missing in the literature and could provide valuable insights into hydrogen effects on the mechanical response of metals such as steel. We adapted existing hydrogen-gas-environment mechanical-testing equipment, which had been designed only for tensile loads, to accommodate the large compressive loads needed to perform strain-life testing. The considerations of these adaptations are discussed. Successful strain-life testing data were acquired from a 4130 pressure vessel steel.


Isolated limb perfusion with tumour necrosis factor-alpha and melphalan for unresectable bone sarcomas of the lower extremity.
Isolated limb perfusion (ILP) with recombinant tumour necrosis factor-alpha (rTNF-alpha) and melphalan has recently been reported to induce major tumour responses and permit limb salvage in over 80% of patients with unresectable soft-tissue sarcomas of the extremities. We investigated whether TNF-based ILP could allow limb-sparing surgery in patients with primary, recurrent or metastatic bone sarcoma to the lower extremity who met the criteria for an amputation and had failed or refused chemotherapy. From August 1992 to December 1997, we employed ILP with rTNF-alpha and melphalan in 13 patients with unresectable bone sarcoma of the lower extremity, all of whom were candidates for amputation. The aim was to reduce tumour size and allow the performance of a limb-sparing surgery (LSS). Following ILP, none of the patients had severe local toxicity and only one patient experienced significant systemic side-effects. LSS was subsequently performed in nine of the 13 patients. LSS was feasible in an additional three patients but was not performed because of the emergence of diffused metastatic disease. ILP with rTNF-alpha and melphalan can allow limb salvage in patients wih locally advanced bone sarcomas who had failed standard treatment options. Its potential role in the treatment of unresectable bone sarcomas of the extremities merits further evaluation.


Are lycopene metabolites metabolically active?
Lycopene is the most abundant carotenoid found in tomatoes and thus has been touted as the bioactive component for the reduced risk of chronic diseases such as prostate cancer. We and others hypothesize that lycopene metabolites are responsible for positively modulating biomarkers and risk factors for the prevention of chronic diseases. Lycopene metabolites circulate in serum and accumulate in tissues at concentrations equivalent to bioactive retinoids. Recent studies report that lycopene metabolites reduce the proliferation of cancer cells, induce apoptosis, enhance gap junction communication between cells, alter normal cell cycle progression, and modulate androgen signaling pathways. Here we review recent literature and provide new evidence to suggest that lycopene metabolites may be bioactive at physiological concentrations.


The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.
Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. Case series, level IV.


Coding of serial order in verbal, visual and spatial working memory.
In the domain of working memory, recent theories postulate that the maintenance of serial order is driven by position marking. According to this idea, serial order is maintained though associations of each item with an independent representation of the position that the item constitutes in the sequence. Recent studies suggest that those position markers are spatial in nature, with the beginning items associated with left side and the end elements with the right side of space (i.e., the ordinal position effect). So far however, it is unclear whether serial order is coded along the same principles in the verbal and the visuospatial domain. The aim of the current study was to investigate whether serial order is coded in a domain general fashion or not. To unravel this question, 6 experiments were conducted. The first 3 experiments revealed that the ordinal position effect is found with verbal but not with spatial information. In the subsequent experiments, the authors isolated the origin of this dissociation and conclude that to obtain spatial coding of serial order, it is not the nature of the encoded information (verbal, visual, or spatial) that is crucial, but whether the memoranda are semantically processed or not. This work supports the idea that serial order is coded in a domain general fashion, but suggests that position markers are only spatially coded when the to-be-remembered information is processed at the semantic level. (PsycINFO Database Record


USP7 reduces the level of nuclear DICER, impairing DNA damage response and promoting cancer progression.
Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl-terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin-protein ligase for DICER. This USP7-MDM2-DICER axis impaired histone γ-H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.


A Library of Polymer-based Microelectrode Array Designs for Recording from the Brain of Different Animal Models.
Large-scale network recording technology is critical in linking neural activity to behavior. Stable, long-term recordings collected from behaving animals are the foundation for understanding neural dynamics and the plasticity of neural circuits. Penetrating microelectrode arrays (MEAs) can obtain high-resolution neural activity from different brain regions. However, ensuring the longevity of implantable devices and the consistency of neural signals over time remains one big challenge. A potential solution is to use flexible, polymer-based MEAs to minimize the foreign body response and prolong the lifetime of neural interfacing devices. Rodents and nonhuman primates (NHP) are commonly used animal models in neuroscience and neuroengineering studies. Specially designed MEAs that capture morphological features of different animal brains and various brain structures are powerful tools to simultaneously obtain neural activities from multiple brain regions. In this work, we develop a set of prototype designs of polymer MEAs that cover cortical, sub-cortical, and multiple brain regions of rodents and NHP.


Differences between HIV-positive and HIV-negative African American men who have sex with men in two major U.S. metropolitan areas.
Alarmingly high HIV prevalence rates among African American men who have sex with men (AAMSM) require the development of effective prevention interventions. In this study of AAMSM conducted in two cities, we explored similarities and differences between HIV-positive and HIV-negative AAMSM on sociodemographic variables, HIV-related risk behaviors, and attitudinal constructs. Differences emerged in several major life areas: (1) poverty, employment, and use of mental health services, (2) sexual risk behaviors, and (3) self-identification with gay identity and culture. With regard to sociodemographic indicators, HIV-positive AAMSM were doing worse than HIV-negative AAMSM in that they were more likely to be disabled, to be living below the poverty level, and accessing mental health services. With regard to risk behaviors and partner characteristics, HIV-positive AAMSM were acting more responsibly than their HIV-negative counterparts, as they were more likely to have used a condom the last time they had sex. In addition, when compared to their HIV-negative counterparts, HIV-positive AAMSM were more likely to have either no casual partners at all or main or casual partners who were HIV-positive, thus preventing new HIV transmission by partnering with other HIV-positive men. Attitudinally, HIV-positive men were more accepting of their sexual attractions to men and were more likely to identify as gay than their HIV-negative peers. Although causality cannot be determined, the findings of this study can be used to strengthen HIV prevention efforts by improving the selection of targeted behaviors and prevention messages for HIV-positive and HIV-negative AAMSM.


Differences in thromboxane A2 synthesis by megakaryocytes and platelets.
The capacity for thromboxane A2 synthesis in response to exogenous arachidonic acid, calcium ionophore A23187, thrombin, and collagen was studied during megakaryocyte maturation. Studies were performed in (1) isolated megakaryocytes not separated, (2) isolated megakaryocytes separated into subgroups at different stages of maturation, and (3) washed platelets. When comparisons were based on equal amounts of cell protein (10(5) megakaryocytes vs 10(8) platelets), isolated megakaryocytes, not separated into subgroups, responded to exogenous arachidonic acid with synthesis of thromboxane A2 equal to that of platelets from the same animals at their respective times of maximum synthesis (30 minutes vs 10 minutes). In similar fashion, megakaryocytes and platelets synthesized thromboxane A2 from endogenous arachidonic acid at the same minimum concentration of A23187, 0.1 mumol/L, and showed equal maximum synthesis at 1 mumol/L (167 +/- 9 pmol and 150 +/- 18 pmol, respectively). In contrast, maximum thromboxane A2 synthesis in response to thrombin (10 U/ml) was three times higher in platelets than in megakaryocytes (230 +/- 15 pmol and 74 +/- 5 pmol, respectively), and synthesis in response to collagen (20 micrograms/ml) was 20 times higher in platelets (130 +/- 20 pmol vs 7 +/- 1.2 pmol). When synthesis was studied in isolated megakaryocytes at different stages of maturation, the capacity for thromboxane A2 synthesis was established in immature megakaryocytes but was not fully developed in the most immature megakaryocytes. Synthesis in response to thrombin was not significantly enhanced by megakaryocyte maturation. Thus the ability to metabolize arachidonic acid occurs early during megakaryocyte maturation, but the ability to respond to thrombin and collagen is only fully established in platelets.


Prediction of neutral noble gas insertion compounds with heavier pnictides: FNgY (Ng = Kr and Xe; Y = As, Sb and Bi).
A novel class of interesting insertion compounds obtained through the insertion of a noble gas atom into the heavier pnictides have been explored by various ab initio quantum chemical techniques. Recently, the first neutral noble gas insertion compounds, FXeY (Y = P, N), were theoretically predicted to be stable; the triplet state was found to be the most stable state, with a high triplet-singlet energy gap, by our group. In this study, we investigated another noble gas inserted compound, FNgY (Ng = Kr and Xe; Y = As, Sb and Bi), with a triplet ground state. Density functional theory (DFT), second order Møller-Plesset perturbation theory (MP2), coupled-cluster theory (CCSD(T)) and multi-reference configuration interaction (MRCI) based techniques have been utilized to investigate the structures, stabilities, harmonic vibrational frequencies, charge distributions and topological properties of these compounds. These predicted species, FNgY (Ng = Kr and Xe; Y = As, Sb and Bi) are found to be energetically stable with respect to all the probable 2-body and 3-body dissociation pathways, except for the 2-body channel leading to the global minimum products (FY + Ng). Nevertheless, the finite barrier height corresponding to the saddle points of the compounds connected to their respective global minima products indicates that these compounds are kinetically stable. The structural parameters, energetics, and charge distribution results as well as atoms-in-molecules (AIM) analysis suggest that these predicted molecules can be best represented as F(-)[(3)NgY](+). Thus, all the aforementioned computed results clearly indicate that it may be possible to experimentally prepare the most stable triplet state of FNgY molecules under cryogenic conditions through a matrix isolation technique.


MELD scores do not predict patient morbidity while on the liver transplant waiting list.
The goals of this study were to assess waitlist morbidity in terms of the frequency of health care services utilized by patients while on the liver transplant (LTX) waiting list and to determine whether that utilization can be predicted by the Model for End-Stage Liver Disease (MELD). Sixty-three noncomatose subjects were followed from waitlist placement until death, change in status, LTX, or study discontinuance. Health care events included doctor/clinic visits, labs, outpatient/inpatient tests and procedures, and hospital/intensive care unit days. Listing MELD scores and LTX MELD scores were examined against the number of health care event occurrences within 60 days of listing and 60 days of LTX, respectively, as were changes in MELD scores between listing and LTX and differences in the number of occurrences between the two time points. The only significant correlations noted were between LTX MELD scores and number of hospital days near LTX (r = .360, P = .046) and between LTX MELD scores and the sum total number of occurrences near LTX (r = .370, P = .044). These results suggest that MELD scores do not appear to predict morbidity in terms of health care utilization in patients awaiting LTX. Developing a system capable of predicting waitlist morbidity may lead to the implementation of medical interventions aimed at circumventing foreseeable complications and/or crises in patients awaiting LTX.


A cell-electrode interface noise model for high-density microelectrode arrays.
A cell-electrode interface noise model is developed which is dedicated to enable the co-simulation of the cell-electrode electrical characteristics, along with the electronics of novel CMOS-based MEA. The electrode noise is investigated for Pt and Pt black electrodes. It is shown that the electrode noise can be the dominant noise source in the full system. Moreover, Pt black electrodes benefit from up to 5 microV(rms) decrease of the electrode output noise, for small electrodes. Furthermore, the cell-electrode interface noise spectral density is shown to be 10 dB to 20 dB larger at 1 kHz when a cell is lying on top of the electrode. This increase depends on the neural cell adhesion on the MEA surface.


Panchromatic symmetrical squaraines: a step forward in the molecular engineering of low cost blue-greenish sensitizers for dye-sensitized solar cells.
Two novel symmetrical blue squaraine sensitizers were synthesized, which exhibit panchromatic light harvesting and a record efficiency over 6% with Jsc exceeding 14 mA cm(-2), and Voc over 620 mV under 1 sun. Their color, low cost, easiness of synthesis, and relatively high photo- and thermal stability open up the way for commercial applications.


[The finite and infinite development. II. Recent psychoanalytic theory and therapeutic considerations].
Freud's characterization of the manifest dream is typified by an implicit appreciation and an explicit devaluation of dream images. According to the author, the theoretical-historical motive behind this divergent evaluation is already evident in Freud's prepsychoanalytic writings, where he assigns primacy to the written word. The author holds that the biographic motive derives from an ambivalent internalization of the Mosaic sanction against graven images, conveyed to Freud by his father through the spirit of the Phillipson Bible.


Selectivity control between Mizoroki-Heck and homo-coupling reactions for synthesising multinuclear metal complexes: unique addition effects of tertiary phosphines and O2.
The addition of a tertiary phosphine and O2 to reaction solutions strongly affected the reactivity and selectivity of coupling reactions between transition metal complexes. The Mizoroki-Heck reaction between metal complexes with bromo and those with vinyl groups in the diimine ligand did not proceed using Pd(OAc)2 in the presence of 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (Sphos) under Ar but proceeded selectively after injection of air into the reaction vessel. In the absence of the phosphine ligand, on the other hand, not only the Mizoroki-Heck reaction but also a homo-coupling reaction between the metal complexes with the bromo groups proceeded at the same time. Mechanistic investigation showed that nanoparticles of Pd species were produced in the absence of the phosphine ligand and worked as catalysts for both the Mizoroki-Heck and homo-coupling reactions. On the other hand, larger Pd particles, which were produced in the presence of Sphos but after addition of air for oxidising Sphos, selectively catalysed the Mizoroki-Heck reaction. 'Molecular' Pd species that were stabilised in the presence of non-oxidised Sphos could not catalyse both coupling reactions under the reaction conditions. Based on these results, reaction conditions were established for the selective progress of the Mizoroki-Heck and the homo-coupling reactions.


Exploration of ecological factors related to the spatial heterogeneity of tuberculosis prevalence in P. R. China.
The current prevalence of tuberculosis (TB) in the People's Republic of China (P. R. China) demonstrates geographical heterogeneities, which show that the TB prevalence in the remote areas of Western China is more serious than that in the coastal plain of Eastern China. Although a lot of ecological studies have been applied in the exploration on the regional difference of disease risks, there is still a paucity of ecological studies on TB prevalence in P. R. China. To understand the underlying factors contributing to the regional inequity of TB burden in P. R. China by using an ecological approach and, thus, aiming to provide a basis to eliminate the TB spatial heterogeneity in the near future. Latent ecological variables were identified by using exploratory factor analysis from data obtained from four sources, i.e. the databases of the National TB Control Programme (2001-2010) in P. R. China, the China Health Statistical Yearbook during 2002-2011, the China Statistical Yearbook during 2002-2011, and the provincial government websites in 2013. Partial least squares path modelling was chosen to construct the structural equation model to evaluate the relationship between TB prevalence and ecological variables. Furthermore, a geographically weighted regression model was used to explore the local spatial heterogeneity in the relationships. The latent ecological variables in terms of 'TB prevalence', 'TB investment', 'TB service', 'health investment', 'health level', 'economic level', 'air quality', 'climatic factor' and 'geographic factor' were identified. With the exception of TB service and health levels, other ecological factors had explicit and significant impacts on TB prevalence to varying degrees. Additionally, each ecological factor had different impacts on TB prevalence in different regions significantly. Ecological factors that were found predictive of TB prevalence in P. R. China are essential to take into account in the formulation of locally comprehensive strategies and interventions aiming to tailor the TB control and prevention programme into local settings in each ecozone.


Physical support with and without optical support: reaction to apprarent depth by chicks and rats.
The locomotor reactions to apparent depth made by chicks and rats were measured in situations offering physical support with and without optical information for support. Chicks avoided an optical void though it provided physical support. Rats responded indifferently to the presence or absence of optical information for support as long as physical support was available.


Artificial insemination history: hurdles and milestones.
Artificial insemination with homologous (AIH) or donor semen (AID) is nowadays a very popular treatment procedure used for many subfertile women worldwide. The rationale behind artificial insemination is to increase gamete density at the site of fertilisation. The sequence of events leading to today's common use of artificial insemination traces back to scientific studies and experimentation many centuries ago. Modern techniques used in human artificial insemination programmes are mostly adapted from the work on cattle by dairy farmers wishing to improve milk production by using artificial insemination with sperm of selected bulls with well chosen genetic traits. The main reason for the renewed interest in artificial insemination in human was associated with the refinement of techniques for the preparation of washed motile spermatozoa in the early years of IVF. The history of artificial insemination is reviewed with particular interest to the most important hurdles and milestones.


Transcription factor short stature homeobox 2 is required for proper development of tropomyosin-related kinase B-expressing mechanosensory neurons.
Dorsal root ganglia (DRG) contain somatosensory neurons of diverse sensory modalities. Among these different types of sensory neurons, the molecular mechanisms that regulate the development and specification of touch neurons are the least well understood. We took a candidate approach and searched for transcription factors that are expressed in subsets of DRG neurons, and found that the transcription factor Shox2 (short stature homeobox 2) is expressed in subpopulations of TrkB (tropomyosin-related kinase B)- and Ret-expressing neurons at neonatal stages. Since TrkB is a known marker that is selectively expressed in touch sensory neurons, we decided to examine the function of Shox2 in specifying TrkB-positive DRG neurons. Conditional deletion of Shox2 in neural crest cells (which give rise to all DRG neurons) caused a 60 ∼ 65% reduction in the number of TrkB-expressing neurons. It also resulted in an increase in coexpression of TrkC in Ret-positive sensory neurons. Deletion of Shox2 in differentiating DRG neurons at later time points caused only a moderate reduction in TrkB expression. Overexpression of Shox2 in all neural crest cells resulted in a small increase in the number of TrkB-expressing neurons. Finally, Shox2 deletion also caused reduced touch sensory axonal innervation to layers III/IV of the spinal cord. Together, our findings identify Shox2 as an essential but not sufficient component of the transcription programs required in neural progenitor cells for the proper specification of subsets of TrkB-expressing touch/mechanosensory neurons.


MR imaging of soft-tissue masses of the foot.
As with other parts of the musculoskeletal system, the soft tissues of the foot can be affected by a wide variety of pathologic entities including trauma, congenital abnormalities, infections, and neoplastic disorders. While plain radiographs are usually the initial examination for evaluation of pathology, magnetic resonance imaging (MRI) is critical to evaluate for abnormalities within the ligaments, tendons, and other nonosseous structures within the foot. The constellation of clinical and MRI findings often allows a relatively specific diagnosis to be rendered. This article discusses both benign and malignant processes within the soft tissues of the foot and presents their characteristic imaging findings with MRI.


Stability of apigeninidin and its methoxylated derivatives in the presence of sulfites.
3-Deoxyanthocyanin pigments are more stable than anthocyanins and show promising bioactive properties. However, little is known about their stability in the presence of food additives such as sulfites. This work investigates the stability of apigeninidin and its derivatives in the presence of sulfites. Pigment (apigeninidin, 5-mono-, and 5,7-dimethoxyapigeninidin) stability at pH 1.8, 3.0, and 5.0, in the presence of sodium metabisulfite (molar ratio ∼ 1:40, pigment/SO2) was monitored over 21 days at room temperature. The structure of sulfite complexation products was monitored using HPLC-MS and NMR spectroscopy. All pigments were significantly bleached within 30 min in the presence of sulfites; the bleaching effect was more severe at pH 5.0 and 3.0 compared to pH 1.8. Apigeninidin was more resistant to bleaching than its methoxylated derivatives. However, all pigments regained some or all of the bleached color within 14-21 days at pH 3.0 and 1.8 in the presence of sulfites, indicating equilibrium favored flavylium cation at these pH values. Formation of colorless sulfonates via bisulfite ion addition at C-4 was responsible for the bleaching effect. Both structure and pH significantly affected stability of 3-deoxyanthocyanidins in the presence of sulfites. The pigments may have potential applications in low pH systems containing sulfites.


Spray dried human and chimpanzee adenoviral-vectored vaccines are thermally stable and immunogenic in vivo.
Cold chain-free vaccine technologies are needed to ensure effective vaccine delivery and coverage, particularly in resource-poor countries. However, the immunogenicity and thermostability of spray dried live viral vector-based vaccines such as recombinant adenoviral-vectored vaccines remain to be investigated. To address this issue, we have spray dried human adenoviral (AdHu5)- and chimpanzee adenoviral (AdCh68)-vectored tuberculosis vaccines in a mannitol and dextran matrix. Spray dried powders containing these two vaccines display the morphologic and chemical properties desired for long-term thermostability and vaccination. Upon reconstitution, they effectively transfected the cells in vitro with relatively small losses in viral infectivity related to the spray drying process. Following in vivo vaccination, AdHu5- and AdCh68-vectored vaccines were as immunogenic as the conventional fresh, cryopreserved liquid vaccine samples. Of importance, even after cold chain-free storage, at ambient temperatures and relatively low humidity for 30 and 90days, the vaccines retained their in vivo immunogenicity, while the liquid vaccine samples stored under the same conditions lost their immune-activating capability almost entirely. Our results support further development of our spray drying technologies for generating thermally stable adenoviral-vectored and other viral-vectored vaccines.


Identification and Profiling Analysis of microRNAs in Guava Fruit (Psidium guajava L.) and Their Role during Ripening.
The guava (Psidium guajava L.) is a climacteric fruit with an accelerated post-harvest overripening. miRNAs are small RNA sequences that function as gene regulators in eukaryotes and are essential for their survival and development. In this study, miRNA libraries were constructed, sequenced and analyzed from the breaker and ripe stages of guava fruit cv. Siglo XXI. One hundred and seventy-four mature miRNA sequences from 28 miRNA families were identified. The taxonomic distribution of the guava miRNAs showed a high level of conservation among the dicotyledonous plants. Most of the predicted miRNA target genes were transcription factors and genes involved in the metabolism of phytohormones such as abscisic acid, auxins, and ethylene, as revealed through an ontology enrichment analysis. The miRNA families miR168, miR169, miR396, miR397, and miR482 were classified as being directly associated with maturation, whereas the miRNA families miR160, miR165, miR167, miR3930, miR395, miR398, and miR535 were classified as being indirectly associated. With this study, we intended to increase our knowledge and understanding of the regulatory process involved in the ripening process, thereby providing valuable information for future research on the ripening of guava fruit.


Microscopic considerations for optimizing silk biomaterials.
Silk is an especially appealing biomaterial due to its adaptable mechanical properties, allowing it to be used in a wide range of tissue engineering applications. However, processing conditions play a critical role in determining silk's mechanical properties, biodegradability, and biocompatibility. While bulk properties of silk have been widely explored, focusing on microscopic features is becoming increasingly important, as modifications at this scale largely affect the resulting regenerative properties of the biomaterial. Structural changes caused by the silk source, extraction, and processing should be carefully considered, as they will affect the biocompatibility and degradability of silk fibroin. Processing techniques and physical properties of silk that make it an ideal material for many biomedical applications will be explored. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Implantable Materials and Surgical Technologies > Nanomaterials and Implants.


Akt‑mediated phosphorylation of Oct4 is associated with the proliferation of stem‑like cancer cells.
Oct4 protein encoded by POU5F1 plays a pivotal role in maintaining the self‑renewal of pluripotent stem cells; however, its presence in cancer cells remains controversial. In the present study, we provided evidence that the transcripts of authentic OCT4 gene (OCT4A) and its multiple pseudogenes were detected in a variety of cancer cell lines. A few major bands were also detected by western blotting using an anti‑Oct4A monoclonal antibody. Moreover, an anti‑Oct4‑pT235 antibody was used to identify a band in the majority of the tested cancer cell lines that coincided with one of the anti‑Oct4A bands which was decreasable by a specific shRNA. The Oct4‑pT235 signals were also detected in human glioblastoma and liver cancer specimens by immunofluorescence microscopy and immunohistochemistry. U87 glioblastoma cells were cultured in a neural stem cell medium to induce the formation of neurospheres rich in stem‑like cancer cells. The levels of Oct4‑pT235 in the sphere cells were markedly increased compared to their monolayer parental cells, a result that was accompanied by upregulation of the PI3K‑Akt pathway. Akti‑1/2, a specific inhibitor of Akt, effectively reduced the level of Oct4‑pT235 and attenuated the proliferation of U87 sphere cells. ITE, an agonist of the aryl hydrocarbon receptor, also significantly attenuated the Akt‑mediated phosphorylation of Oct4 in glioblastoma and liver cancer cells, and reduced their tumorigenic potential in a xenograft tumor model. Taken together, we concluded that the Akt‑mediated phosphorylation of Oct4A or its homolog protein was associated with the proliferation of stem‑like cancer cells that may serve as a novel biomarker and drug target for certain types of cancer.


Mid term effects of pulmonary thromboendarterectomy on clinical and cardiopulmonary function status.
Chronic thromboembolic pulmonary hypertension (CTEPH) can be successfully treated surgically by pulmonary thromboendarterectomy (PTE) but there are few data on mid-term cardiopulmonary function, particularly on exertion, and clinical benefits following pulmonary PTE. A 2 year follow up study was undertaken of clinical status, haemodynamic and lung function indices, gas exchange, and exercise tolerance in 38 patients of mean (SD) age 50 (15) years who had undergone PTE. In-hospital mortality was about 10%. Before PTE all the patients were severely impaired (NYHA classes III-IV). There was no time difference in the improvement in the parameters: nearly all the improvement in cardiac output, gas exchange, and clinical status was achieved in the first 3 months as a result of the relief of pulmonary obstruction. At 3 months the percentage of patients with normal cardiac output and PaO(2) and of those with reduced clinical impairment increased to 97%, 59%, and 87%, respectively, without any further change. Only mean pulmonary artery pressure (mPAP), carbon monoxide transfer factor (TLCO), and exercise tolerance improved gradually during the second year, probably due to the recovery of the damaged small vessels. TLCO was overestimated before PTE but afterwards the trend was similar to that of mPAP. At mid term only a few patients did not have a satisfactory recovery because of lack of operative success, hypertension relapse, or the effect of preoperative hypertension on vessels in non-obstructed segments. Most of the patients, even the more compromised ones, had excellent long lasting results.


Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary.
Oxidative stress has been implicated in various aspects of aging, but the role of oxidative stress in ovarian aging remains unclear. Our previous studies have shown that the initiation of apoptotic cell death in ovarian follicles and granulosa cells by various stimuli is initiated by increased reactive oxygen species. Herein, we tested the hypothesis that ovarian antioxidant defenses decrease and oxidative damage increases with age in mice. Healthy, wild-type C57BL/6 female mice aged 2, 6, 9, or 12 mo from the National Institute on Aging Aged Rodent Colony were killed on the morning of metestrus. Quantitative real-time RT-PCR was used to measure ovarian mRNA levels of antioxidant genes. Immunostaining using antibodies directed against 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) was used to localize oxidative lipid, protein, and DNA damage, respectively, within the ovaries. TUNEL was used to localize apoptosis. Ovarian expression of glutathione peroxidase 1 (Gpx1) increased and expression of glutaredoxin 1 (Glrx1), glutathione S-transferase mu 2 (Gstm2), peroxiredoxin 3 (Prdx3), and thioredoxin 2 (Txn2) decreased in a statistically significant manner with age. Statistically significant increases in 4-HNE, NTY, and 8-OHdG immunostaining in ovarian interstitial cells and follicles were observed with increasing age. Our data suggest that the decrease in mRNA expression of mitochondrial antioxidants Prdx3 and Txn2 as well as cytosolic antioxidants Glrx1 and Gstm2 may be involved in age-related ovarian oxidative damage to lipid, protein, DNA, and other cellular components vital for maintaining ovarian function and fertility.


[Safety of levetiracetam as adjunctive therapy in epilepsy: the SKATE trial in Spain].
To continue assessing safety and to evaluate the efficacy of levetiracetam and to assess the optimal dose in community based practice. Single-arm, open label, multicenter, observational and prospective trial lasting 16-22 weeks. Criteria for inclusion: patients > 16 years experiencing epilepsy with partial seizures taking at least one concomitant antiepileptic drug. The initial dose was 1,000 mg/day, up to the maximal dose of 3,000 mg/day. Safety evaluation was adverse events reporting. Efficacy evaluation were reduction in seizure frequency; QOLIE-10 questionnaire and global evaluation scale of disease severity. Of the 342 subjects, 296 (86.5%) completed the treatment period. 103 subjects (30.1%) experienced at least one adverse event. The most frequently adverse events reported were somnolence (11.7%), dizziness (5.8%) and headache (3.5%). The events were majority (93.1%) of mild to moderate intensity. The median percent reduction in partial seizure frequency per week was 55%. 51.2% of patients experienced a reduction 50% in partial seizure frequency. Similar results were observed for total seizures. An increase of QOLIE-10 total score was observed (10.2 +/- 17.8). A total of 63.5% patients were rated as having moderate or marked improvement in their disease severity. These data confirm and provide additional support of levetiracetam safety and efficacy demonstrated in phase III trials.


Audit of antibiotic prescribing in two governmental teaching hospitals in Indonesia.
This article estimates the magnitude and quality of antibiotic prescribing in Indonesian hospitals and aims to identify demographic, socio-economic, disease-related and healthcare-related determinants of use. An audit on antibiotic use of patients hospitalized for 5 days or more was conducted in two teaching hospitals (A and B) in Java. Data were collected by review of records on the day of discharge. The method was validated through concurrent data collection in Hospital A. Multivariate logistic regression analysis was performed to determine variables to explain antibiotic prescribing. Prescriptions were assessed by three reviewers using standardized criteria. A high proportion (84%) of 999 patients (499 in Hospital A and 500 in Hospital B) received an antibiotic. Prescriptions could be categorized as therapeutic (53%) or prophylactic (15%), but for 32% the indication was unclear. Aminopenicillins accounted for 54%, and cephalosporins (mostly third generation) for 17%. The average level of antibiotic use amounted to 39 DDD/100 patient-days. Validation revealed that 30% of the volume could be underestimated due to incompleteness of the records. Predictors of antibiotic use were diagnosis of infection, stay in surgical or paediatric departments, low-cost nursing care, and urban residence. Only 21% of prescriptions were considered to be definitely appropriate; 15% were inappropriate regarding choice, dosage or duration, and 42% of prescriptions, many for surgical prophylaxis and fever without diagnosis of infection, were deemed to be unnecessary. Agreement among assessors was low (kappa coefficients 0.13-0.14). Despite methodological limitations, recommendations could be made to address the need for improving diagnosis, treatment and drug delivery processes in this setting.


Re-operation after laparoscopic adjustable gastric banding leads to a further decrease in BMI and obesity-related co-morbidities: results in 33 patients.
Laparoscopic adjustable gastric banding (LAGB) is a safe technique with few direct postoperative complications. However, long-term complications such as slippage and pouch dilatation are a well-known problem and re-operations are necessary in a substantial number of patients. In this study, the results of laparoscopic re-operations after LAGB are evaluated. 33 patients had a re-operation because of failed LAGB. 29 patients had major re-operation and 4 patients minor re-operation under local anesthesia. The charts of these patients were retrospectively studied. Mean time between the first band placement and re-operation was 28.1 +/- 17.6 months. The cause of band dysfunction was anterior slippage (n=17), band erosion (n=5), band intolerance (n=3), posterior slippage (n=2) and band leakage (n=2). Symptoms of band dysfunction were vomiting (n=16), pyrosis (n=13), nausea (n=8), retrosternal pain (n=11) and regurgitation (n=5). Laparoscopic refixation of the band was performed in 19 patients: the band was replaced in 4 patients while in 1 patient the band was removed; in 3 patients, the laparoscopic procedure was converted to open surgery; 5 patients underwent conversion to a bypass procedure (biliopancreatic diversion in 3 and gastric bypass in 2). There were no direct postoperative complications except for wound infections (n=2). Postoperative follow-up was 100% with a mean period of 34 +/- 19 months. BMI decreased further from 37.5 +/- 6.4 kg/m(2) before re-operation to 33 +/- 7 kg/m(2). Obesity-related co-morbidity also decreased further or completely dissolved. 3 patients (9%) again developed anterior slippage and a second laparoscopic re-operation was necessary. A laparoscopic re-operation for band-related complications after LAGB is safe and feasible. With band slippage, a laparoscopic refixation was possible in 89%. Re-operation leads to further decrease in BMI and obesity-related co-morbidities.


A new short rib syndrome: report of two cases.
We describe two unrelated malformed infants who died shortly after birth and who had multiple congenital anomalies including hydrops and ascites, facial abnormalities (with median cleft of the upper lip), narrow thorax, protuberant abdomen, and short, bowed limbs. Postmortem radiographs showed very short ribs and disproportionately short long tubular bones; no metaphyseal abnormalities were present. Comparison with earlier described short-rib/short-rib-polydactyly syndromes suggest that the disorder present in our two cases is a new type of short-rib syndrome. One of our patients was born to a consanguineous couple; in a subsequent pregnancy, real-time ultrasonography in the second trimester showed that the female fetus had the same abnormalities as its sib. Diagnosis was confirmed after elective abortion. This suggests that this short-rib syndrome may be an autosomal recessive disorder.


Pilocarpine toxicity in retinal ganglion cells.
Muscarinic agents reduce intraocular pressure by enhancing aqueous outflow, probably by stimulating ciliary muscle contraction. However, pilocarpine is a well characterized neurotoxin and is widely used to generate animal seizure models. It was therefore investigated whether pilocarpine was also toxic to retinal ganglion cells. Dissociated whole retinal preparations were prepared from postnatal day 16 to 19 rats. Retinal ganglion cells had been previously back-labeled with a fluorescent tracer. Retinal cells were incubated with pilocarpine, lithium, and inositol derivatives, and viability of the retrogradely labeled retinal ganglion cells was assayed after 24 hours. Pilocarpine was toxic to retinal ganglion cells in a dose-dependent fashion. This toxicity was potentiated by lithium and blocked by epi- and myo-inositol. Pilocarpine is toxic to retinal ganglion cells in a mixed culture assay. This toxicity appears to depend on the inositol pathway and is similar to its mode of action in other neurons. However, 0.4 mM pilocarpine (the lowest concentration that did not affect ganglion cell survival) is roughly 1000-fold higher than the vitreal concentration and 20-fold higher than the scleral concentration that can be obtained with topical administration of 2% pilocarpine in the rabbit eye.


The structure of a glycoside hydrolase family 81 endo-β-1,3-glucanase.
Endo-β-1,3-glucanases catalyze the hydrolysis of β-1,3-glycosidic linkages in glucans. They are also responsible for rather diverse physiological functions such as carbon utilization, cell-wall organization and pathogen defence. Glycoside hydrolase (GH) family 81 mainly consists of β-1,3-glucanases from fungi, higher plants and bacteria. A novel GH family 81 β-1,3-glucanase gene (RmLam81A) from Rhizomucor miehei was expressed in Escherichia coli. Purified RmLam81A was crystallized and the structure was determined in two crystal forms (form I-free and form II-Se) at 2.3 and 2.0 Å resolution, respectively. Here, the crystal structure of a member of GH family 81 is reported for the first time. The structure of RmLam81A is greatly different from all endo-β-1,3-glucanase structures available in the Protein Data Bank. The overall structure of the RmLam81A monomer consists of an N-terminal β-sandwich domain, a C-terminal (α/α)6 domain and an additional domain between them. Glu553 and Glu557 are proposed to serve as the proton donor and basic catalyst, respectively, in a single-displacement mechanism. In addition, Tyr386, Tyr482 and Ser554 possibly contribute to both the position or the ionization state of the basic catalyst Glu557. The first crystal structure of a GH family 81 member will be helpful in the study of the GH family 81 proteins and endo-β-1,3-glucanases.


Associations between evidence-based practice and mental health outcomes in child and adolescent mental health services.
The effectiveness of evidence-based practice in the treatment of children with conduct disorder (n = 186) or emotional disorders (n = 490) in routine care was examined using naturalistic, previously collected data from 30 child and adolescent mental health services. Repeated measures analysis of covariance was used to compare the outcomes of children who received parent training for conduct disorder and cognitive behavioural therapy for emotional disorders (evidence-based practice) with children who did not receive these treatments (non-evidence-based practice). There was a relatively low occurrence of evidence-based practice, particularly for children with conduct disorder. Both the evidence-based practice and non-evidence-based practice groups improve over time, with moderate effect sizes, and there were greater improvements associated with evidence-based practice for children with emotional disorders, based on child self-reported symptoms but not on parent report. In the present sample, significant differences were not found for conduct disorder. Findings provide tentative support for evidence-based practice for the treatment of emotional disorders in routine care settings.


Topical corticosteroid therapy and pituitary-adrenal function.
Systemic absorption has been reported after the use of corticosteroid eye drops. Prolonged use could result in adrenocortical insufficiency and an associated adrenal crisis under stressful situations. For that reason, we studied the hypothalamic-pituitary-adrenal axis of patients receiving corticosteroid eye drope. Fifteen patients were given 0.1% dexamethasone sodium phosphate eye drops, one drop (approximately 1/30 ml) to each eye four times a day for six weeks. This dosage resulted in partial adrenal suppression, manifested by reduced levels of plasma cortisol. However, in each case, the hypothalamic-pituitary-adrenal axis, as evaluated with the use of the oral metyrapone tartrate test, was intact.


Enhancing Community Suicide Risk Assessment and Protective Intervention Action Plans Through a Bystander Intervention Model-Informed Video.
Aim: The effects of a bystander intervention model (BIM)-informed intervention (video) for the general community on participant risk of suicide assessment ability (ROSAA) and protective intervention ability (PIA) were compared with an active control (non-BIM-informed video). Method: Video interventions with 628 participants (Mage = 47.99, SDage = 17.34, range = 18-85 years) were conducted online. ROSAA and PIA were assessed immediately preintervention, postintervention, and at 2 months follow-up (n = 126). Results: Linear mixed model analyses indicated that the experimental and control conditions improved on both outcome variables postintervention/Time 2 (T2); however, the former yielded better outcomes than the latter (moderate ESs in both variables). Follow-up/Time 3 (T3) experimental ROSAA scores were higher than Time 1 (T1) and lower than T2 scores. Follow-up experimental PIA scores were higher than T1 and lower than T2 scores. Follow-up control ROSAA scores were higher than those of T1 and similar to T2. Follow-up control PIA scores were similar to T1 and T2 scores. Limitations: Limitations of the study include: sample homogeneity, small n at follow-up, self-report data only (no observable behavior was tested), fair inter-rater reliability, and a brief follow-up time frame. Conclusion: Current community information increased ROSAA and PIA. A BIM-informed intervention significantly enhanced these effects, which seemed to wane somewhat over time with the effect being lower at follow-up compared with postintervention. The BIM should be explored further as a basis for community suicide prevention interventions.


Two-level tuning of fuzzy PID controllers.
Fuzzy PID tuning requires two stages of tuning; low level tuning followed by high level tuning. At the higher level, a nonlinear tuning is performed to determine the nonlinear characteristics of the fuzzy output. At the lower level, a linear tuning is performed to determine the linear characteristics of the fuzzy output for achieving overall performance of fuzzy control. First, different fuzzy systems are defined and then simplified for two-point control. Non-linearity tuning diagrams are constructed for fuzzy systems in order to perform high level tuning. The linear tuning parameters are deduced from the conventional PID tuning knowledge. Using the tuning diagrams, high level tuning heuristics are developed. Finally, different applications are demonstrated to show the validity of the proposed tuning method.


Frequency of urinary tract infection in renal transplant recipients and effect on graft function.
To determine the risk factors of urinary tract infection in renal transplant recipients and its effect on graft function among transplanted patients visiting the outpatients department of Sindh Institute of Urology and Transplantation. This cohort study was conducted at Transplantation department, Sindh Institute of Urology and Transplantation Karachi. The period of the study enrollment extended from April 2008 to September 2008 included were two hundred adult live related renal transplant recipients who were enrolled during the initial post transplant period and followed up for one year. Analysis was done by using SPSS ver 10.0. The level of significance was taken as 0.05. Student's t test and chi square test were used to compare the variables in both groups. The mean age of the patients was 30 +/- 10 years. Sixty six (33%) renal transplant recipients had at least one episode of urinary tract infection which occurred in 51 (77%) patients during the first two months after renal transplant and 8 (12%) patients had recurrence of infection. Gram negative bacilli were the principally isolated agents. E. coli was found in 34 (51%) patients and Pseudomonas in 12 (18%). Renal stone disease, structural abnormalities, delays in Foleys removal, and post operation hospital stay were statistically significant risk factors for urinary tract infection in the patients. Twenty three recipients of the study developed early graft dysfunction due to urinary tract infection. No graft was lost in either groups. Structural abnormalities, renal stone disease, delay in removal of Foley's catheter and increased post transplant hospital stay are risk factors leading to UTI in renal transplant recipients.


Response of a vulnerable barrier island to multi-year storm impacts: LiDAR-data-inferred morphodynamic changes on Ship Island, Mississippi, USA.
Barrier systems around the world are experiencing accelerated sea-level rise, reduced sediment supply, and frequent hurricane impacts. However, detailed quantitative field-based studies concerning the response to these external forcing mechanisms are scarce, particularly on the scale of entire islands. The Mississippi - Alabama barrier island chain, located along the U.S. Gulf of Mexico coastline has lost land on the order of hectares per year since records began in the 1840s, putting mainland coastal communities and important ecosystems at risk. Here we present an analysis of Light Detection and Ranging (LiDAR) digital elevation models, revealing erosional/depositional patterns and geomorphologic changes around the most vulnerable of these islands, Ship Island. Four LiDAR datasets (2004, 2007, 2010, and 2012), capturing the complete topography of the island and some bathymetry in the inlet and surrounding shallows to depths of up to 8 m, are used to investigate subaerial and subaqueous sediment volume changes between these years. The impact of Hurricane Katrina, which produced the highest storm surge ever recorded in the United States, is captured in the 2004-2007 dataset. During this time, sediment comparable to 1.5 times the 2004 subaerial island volume was lost from the area included in the topographic/bathymetric dataset. Only 1/5 of this volume was recovered to this area between 2007 and 2010. The island returned to a state of sediment loss between 2010 and 2012, albeit within the error bounds, while the areal extent of the islands continued to increase. This study examines the impact severe storm events can have on vulnerable barrier islands. It highlights the importance of utilizing 3D datasets that include both topographic and bathymetric data for morphodynamic analyses of barrier island systems.


Machine learning for surrogate process models of bioproduction pathways.
Technoeconomic analysis and life-cycle assessment are critical to guiding and prioritizing bench-scale experiments and to evaluating economic and environmental performance of biofuel or biochemical production processes at scale. Traditionally, commercial process simulation tools have been used to develop detailed models for these purposes. However, developing and running such models can be costly and computationally intensive, which limits the degree to which they can be shared and reproduced in the broader research community. This study evaluates the potential of an automated machine learning approach to develop surrogate models based on conventional process simulation models. The analysis focuses on several high-value biofuels and bioproducts for which pathways of production from biomass feedstocks have been well-established. The results demonstrate that surrogate models can be an accurate and effective tool for approximating the cost, mass and energy balance outputs of more complex process simulations at a fraction of the computational expense.


A Common Variant and the Transcript Levels of MC4R Gene Are Associated With Adiposity in Children: The IDEFICS Study.
The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake. The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children. The Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1). A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses. Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively. At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P < .001). No association was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633. The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2-9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat.


Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study.
Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at several sites, particularly in the upper gastrointestinal tract. However, the role of dietary intake of BaP and cancer in humans is not clear. We created a BaP database of selected food products that could be linked to Food Frequency Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each food line-item (composite samples) which consisted of a variety of foods in a FFQ. Composite sample parts were derived from the Second National Health and Nutrition Examination Survey (NHANES II) which represents the most common food items consumed by the general population. Meat samples were cooked by different techniques in controlled conditions, and by various restaurants and fast-food chains. Non-meat products were purchased from the major national supermarket chains. The quantities of BaP were measured using a thin-layer chromatography (TLC)/spectrofluorometer technique and were highly correlated with both BaP (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC technique. We linked our database to the results from a FFQ and estimated the daily BaP intake of various food items in 228 subjects in the Washington, DC metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked meat) were found in grilled/barbecued very well done steaks and hamburgers and in grilled/barbecued well done chicken with skin. BaP concentrations were lower in meats that were grilled/barbecued to medium done and in all broiled or pan-fried meat samples regardless of doneness level. The BaP levels in non-meat items were generally low. However, certain cereals and greens (e.g. kale, collard greens) had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean daily intake of BaP. This database may be helpful in initial attempts to assess dietary BaP exposures in studies of cancer etiology.


Influence of long-term feeding of limited amounts of phosphorus on dry matter intake, milk production, and body weight of dairy cows.
For almost two lactations, 24 high-yielding, multiparous dairy cows were fed a basal diet and concentrate mixtures with three different P concentrations. The basal diet consisted of grass (silage or artificially dried), corn silage, wet beet pulp, straw, and concentrates. The concentrate mixtures differed only in P content by varying the amount of monosodium phosphate. The number of cows and the amount of dietary P, expressed as a percentage of current recommendations in the Netherlands were: 6 cows, 100% (P100); 9 cows, 80% (P80); and 9 cows, 67% (P67). This resulted in dietary P concentrations of 3.3, 2.8, and 2.4 g/kg of dietary DM for the P100, P80, and P67 treatments, respectively. The trial lasted for 21 mo, including two lactations and two dry periods. Feed intake of the P67 group was reduced significantly during the first dry period. Dry matter intake, milk yield, and body weight were all reduced with the low P treatment during the second lactation. Phosphorus had no effect on reproductive performance. Between P100 and P80, no effect on any of the variables in this trial was observed. Results suggests that the diet with 2.8 g of P/kg of dietary DM proved to be sufficient to meet the P requirement of dairy cows producing approximately 9000 kg of milk per lactation.


Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study.
Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer. In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783. 91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]). Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed. AstraZeneca.


Theta-burst Transcranial Magnetic Stimulation Alters the Functional Topography of the Cortical Motor Network.
Transcranial magnetic stimulation (TMS) is a non-invasive tool that is able to modulate the electrical activity of the brain depending upon its protocol of stimulation. Theta burst stimulation (TBS) is a high-frequency TMS protocol that is able to induce prolonged plasticity changes in the brain. The induction of plasticity-like effects by TBS is useful in both experimental and therapeutic settings; however, the underlying neural mechanisms of this modulation remain unclear. The aim of this study was to investigate the effects of continuous TBS (cTBS) on the intrahemispheric and interhemispheric functional connectivity of the resting and active brain. A total of 26 healthy humans were randomly divided into two groups that received either real cTBS or sham (control) over the left primary motor cortex. Surface electroencephalogram (EEG) was used to quantify the changes of neural oscillations after cTBS at rest and after a choice reaction time test. The cTBS-induced EEG oscillations were computed using spectral analysis of event-related coherence (ERCoh) of theta (4-7.5 Hz), low alpha (8-9.5 Hz), high alpha (10-12.5 Hz), low beta (13-19.5 Hz), and high beta (20-30 Hz) brain rhythms. We observed a global decrease in functional connectivity of the brain in the cTBS group when compared to sham in the low beta brain rhythm at rest and high beta brain rhythm during the active state. In particular, EEG spectral analysis revealed that high-frequency beta, a cortically generated brain rhythm, was the most sensitive band that was modulated by cTBS. Overall, our findings suggest that cTBS, a TMS protocol that mimics the mechanism of long-term depression of synaptic plasticity, modulates motor network oscillations primarily at the cortical level and might interfere with cortical information coding.


Are state minimum jail laws associated with less frequent drunk-driving?
The current study investigated associations between minimum jail sentences included in state DUI laws and self-reported drunk-driving in the US. Scant existing research has been conducted on this topic. The current study is the first to use Behavioral Risk Factor Surveillance System (BRFSS) data to investigate associations between minimum jail sentences and frequency of self-reported drunk-driving among adults who report drunk-driving. 2020 BRFSS data were used. Analyses were limited to participants aged 18 years and older who reported at least one episode of drunk-driving during the past 30-days. Participants missing data on age, gender, race, income, binge-drinking, or state of residence were excluded from analyses. The final sample size was 3,732. Websites from official state legislatures and/or data from state motor vehicle departments were used to gather current information on DUI minimum jail penalties. A dichotomous variable was created that categorized all 50 states and Washington D.C. as either (i) having a minimum jail sentence for first time DUI offense or (ii) having no minimum jail sentence for first time DUI offense. Multivariable negative binomial regression analyses were conducted using SAS® v9.4. The dependent variable was the number of self-reported drunk-driving episodes. Among the sample of adults who reported drunk-driving, residents of states with no minimum jail sentence for a first-time DUI offense had a 32% higher incidence rate of drunk-driving episodes [RR = 1.32,95% CI:0.98-1.77] compared to their counterparts residing in states with a minimum jail sentence for first time DUI offenses. Similar findings were observed in multiple sensitivity analyses conducted. There was a marginally significant [p = 0.07] higher incidence rate of drunk-driving episodes among residents of states with no minimum jail sentence compared to those in states with a minimum jail sentence for the first time DUI. This was the first study to use BRFSS 2020 data to investigate this association and only among participants who self-reported drunk-driving. We therefore provide an important contribution to the literature on this association by using the most up to date data and among a valid sample of drunk drivers. Further studies that provide stronger causal inference are needed.


Voltammetric detection of sequence-selective DNA hybridization related to Toxoplasma gondii in PCR amplicons.
This work describes the single-use electrochemical DNA biosensor technology developed for voltammetric detection of sequence selective DNA hybridization related to important human and veterinary pathogen; Toxoplasma gondii. In the principle of electrochemical label-free detection assay, the duplex of DNA hybrid formation was detected by measuring guanine oxidation signal occured in the presence of DNA hybridization. The biosensor design consisted of the immobilization of an inosine-modified (guanine-free) probe onto the surface of pencil graphite electrode (PGE), and the detection of the duplex formation in connection with the differential pulse voltammetry(DPV) by measuring the guanine signal. Toxoplasma gondii capture probe was firstly immobilized onto the surface of the activated PGE by wet adsorption. The extent of hybridization at PGE surface between the probe and the target was then determined by measuring the guanine signal observed at +1.0V. The electrochemical monitoring of optimum DNA hybridization has been performed in the target concentration of 40µg/mL in 50min of hybridization time. The specificity of the electrochemical biosensor was then tested using non-complementary, or mismatch short DNA sequences. Under the optimum conditions, the guanine oxidation signal indicating full hybridization was measured in various target concentration from 0.5 to 25µg/mL and a detection limit was found to be 1.78µg/mL. This single-use biosensor platform was successfully applied for the voltammetric detection of DNA hybridization related to Toxoplasma gondii in PCR amplicons.


The mechanism of action of lymphokines. IX. The enzymatic basis of hydrogen peroxide production by lymphokine-activated macrophages.
The purpose of this study was to elucidate the biochemical basis of the enhanced hydrogen peroxide (H2O2) production by guinea pig peritoneal macrophages (MP) cultured in lymphokine (LK)-containing medium. The markedly augmented H2O2 generation by these cells, demonstrable by the horseradish peroxidase (HRP)-catalyzed oxidation of phenol red, is distinguished by its lack of dependence on a second stimulus. We demonstrate that H2O2 production is truly spontaneous and is not caused by a stimulant present among the H2O2 assay reagents. The principal candidate for such a role was HRP type II (a mixture of five isoenzymes) that was reported to be capable of eliciting an oxidative burst in MP. Four distinct HRP isoenzymes that were found incapable of provoking an oxidative response were nevertheless adequate for demonstrating H2O2 production by LK-activated MP. Blocking the MP receptor for mannose by the addition of mannan to the assay system resulted in enhanced detection of H2O2 by low concentrations of HRP type II and by three out of four HRP isoenzymes. Treatment of MP with LK-containing medium for 72 hr did not result in a significant change in the activity of cellular superoxide dismutase (SOD) compared with MP cultured for the same length of time in control medium. By using the specific inhibitor of copper, zinc-containing SOD, sodium diethyldithiocarbamate (DDC), and the universal SOD inhibitor, sodium nitroprusside, we found that the predominant enzyme in guinea pig peritoneal MP is probably manganese-containing SOD. Incubation of LK-activated MP with nitroprusside resulted in almost total inhibition of H2O2 production and a simultaneous switch to superoxide (O2-) liberation. Similar exposure to DDC had no effect. These data indicate that H2O2 produced by LK-activated MP is derived exclusively by enzymatic dismutation of O2- mediated by a manganese-containing SOD. The increase in spontaneous H2O2 production induced by LK is therefore secondary to augmented O2- production that occurs at a cellular location where O2- is accessible to SOD. The enzymatic basis of the enhanced oxygen radical production was investigated by determining the kinetic parameters of the O2- -forming NADPH oxidase of resting LK-treated MP in a cellfree system in which O-2 production was induced by sodium dodecyl sulfate. The Km for NADPH and the Vmax of the enzyme of LK-treated MP were not different from those of the enzyme of MP incubated in control medium. We conclude that LK treatment of MP does not modulate the NADPH oxidase itself but, most likely, a process related to activation of the enzyme.


Laparoscopic sentinel lymph node detection after hysteroscopic injection of technetium-99 in patients with endometrial cancer.
Endometrial cancer (EC) has an increasing incidence worldwide. Despite the unequivocal prognostic importance of nodal status, systematic lymphadenectomy is associated to elevated morbidity. Sentinel lymph node (SLN) biopsy is designed to avoid extensive nodal dissection and provide crucial oncologic information. The goal of this prospective study was to determine the feasibility, safety, and accuracy of laparoscopic SLN biopsy in EC obtained through hysteroscopic injection of technetium-99 (Tc-99). From January 2008 to December 2012, a total of 42 women with EC were included in the study. We injected 20 mBq of Tc-99 hysteroscopically underneath the tumor minutes before definitive surgery. Thereafter, laparoscopic SLN identification /biopsy followed by pelvic and para-aortic lymphadenectomy, hysterectomy, and bilateral salpingo-oophorectomy were executed. The total number of removed nodes was 970. The detection rate of the method was 73% (31/42). Among the 70 isolated SLNs, 35% (24) were exclusively identified in the para-aortic area. Fourteen patients (45%) had SLN only in the pelvic region, whereas 11 (35%) had SLN in both pelvic and para-aortic areas and 6 women (20%) had isolated para-aortic SNL. Nodal metastases were histologically confirmed in 9 patients (22%), and SLN was identified in 7 of 9 patients (78%). Although the obtained specificity was 100% and the negative predictive value was 89%, the sensitivity was only 58% (false-negative rate of 42%). We could demonstrate that endoscopic SLN biopsy obtained through hysteroscopic injection of Tc-99 is a feasible and safe method. Despite the restricted number of included patients in this series, the obtained sensitivity and false-negative rates raise some questions about the real accuracy of the procedure in EC. Larger validation trials requiring quality pelvic and para-aortic lymphadenectomy are essential to correctly evaluate the method.


[The impact of food allergy in patients with atopic dermatitis].
Besides other trigger factors food allergens have been shown to play a major role in the exacerbation and maintenance of eczematous lesions in patients with atopic dermatitis (AD), particularly in children. Food allergy may not only present as a flare up up of eczema in these patients, but also immediate type reactions and mixed reactions can be observed under food challenge tests. Whereas cow's milk hen's egg, wheat and soy have been identified as important triggers in infants, pollen related foods like nuts, fruit und vegetable have a greater impact in adolescents and adult Food specific T cells have been identified as effector cells in food responsible eczema and food specific T cell clones could be generated from lesional skin of patients who reacted with a worsening of their AD upon oral challenge tests. Due to the poor reliability of in-vitro (RAST) and skin tests (skin prick test (SPT), atopy patch test (APT)) the double blind placebo controlled food challenge (DBPCFC) is regarded as the gold standard in the diagnostic work-up of food allergy. Once a food allergy has been diagnosed, a specific elimination diet represents the first line therapy, which has to consider the supplementation of essential nutrients.