Long-term continence and patient satisfaction after artificial sphincter implantation for urinary incontinence after prostatectomy.
We assess long-term continence and patient satisfaction after implantation of the AMS Sphincter 800 (American Medical Systems, Minnetonka, Minnesota) in men who were incontinent after total and subtotal prostatectomy. Patients who had an artificial urinary sphincter implanted for urinary incontinence after prostatectomy and a minimum of 20 months of followup were identified from a patient database. The medical records of these 209 patients were reviewed, and a questionnaire was mailed. Telephone contact was attempted with patients who did not respond to the questionnaire. Of the 209 patients 11 (5%) had undergone device removal, 34 (16%) were deceased and an additional 51 (24%) could not be contacted for followup. Our study group consisted of the 113 patients with artificial urinary sphincters who could be contacted for followup. Mean followup was 73 months (range 20 to 170). There were 4 (4%) patients who were dry and continent and 68 (60%) were incontinent using 0 to 1 pad daily. An additional 35 (31%) patients required 2 to 3 pads daily and 5 (4%) used more than 3 daily. There were 14 (12%) patients who had undergone surgical revision of the device. Of the 113 patients 31 (28%) were very satisfied, 50 (45%) satisfied, 20 (18%) neutral, 7 (6%) dissatisfied and 4 (4%) very dissatisfied. One patient was not using his device to control continence. Artificial urinary sphincter implantation offers men who are incontinent after prostatectomy a reasonable chance for obtaining long-term satisfactory urinary control, although complete continence is unusual.


Genomic organization and promoter cloning of the human X11α gene APBA1.
X11α is a brain specific multi-modular protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). Aggregation of amyloid-β peptide (Aβ), an APP cleavage product, is believed to be central to the pathogenesis of Alzheimer's disease. Recently, overexpression of X11α has been shown to reduce Aβ generation and to ameliorate memory deficit in a transgenic mouse model of Alzheimer's disease. Therefore, manipulating the expression level of X11α may provide a novel route for the treatment of Alzheimer's disease. Human X11α is encoded by the gene APBA1. As evidence suggests that X11α expression can be regulated at transcription level, we have determined the gene structure and cloned the promoter of APBA1. APBA1 spans over 244 kb on chromosome 9 and is composed of 13 exons and has multiple transcription start sites. A putative APBA1 promoter has been identified upstream of exon 1 and functional analysis revealed that this is highly active in neurons. By deletion analysis, the minimal promoter was found to be located between -224 and +14, a GC-rich region that contains a functional Sp3 binding site. In neurons, overexpression of Sp3 stimulates the APBA1 promoter while an Sp3 inhibitor suppresses the promoter activity. Moreover, inhibition of Sp3 reduces endogenous X11α expression and promotes the generation of Aβ. Our findings reveal that Sp3 play an essential role in APBA1 transcription.


A large sequenced mutant library - valuable reverse genetic resource that covers 98% of sorghum genes.
Mutant populations are crucial for functional genomics and discovering novel traits for crop breeding. Sorghum, a drought and heat-tolerant C4 species, requires a vast, large-scale, annotated, and sequenced mutant resource to enhance crop improvement through functional genomics research. Here, we report a sorghum large-scale sequenced mutant population with 9.5 million ethyl methane sulfonate (EMS)-induced mutations that covered 98% of sorghum's annotated genes using inbred line BTx623. Remarkably, a total of 610 320 mutations within the promoter and enhancer regions of 18 000 and 11 790 genes, respectively, can be leveraged for novel research of cis-regulatory elements. A comparison of the distribution of mutations in the large-scale mutant library and sorghum association panel (SAP) provides insights into the influence of selection. EMS-induced mutations appeared to be random across different regions of the genome without significant enrichment in different sections of a gene, including the 5' UTR, gene body, and 3'-UTR. In contrast, there were low variation density in the coding and UTR regions in the SAP. Based on the Ka /Ks value, the mutant library (~1) experienced little selection, unlike the SAP (0.40), which has been strongly selected through breeding. All mutation data are publicly searchable through SorbMutDB (https://www.depts.ttu.edu/igcast/sorbmutdb.php) and SorghumBase (https://sorghumbase.org/). This current large-scale sequence-indexed sorghum mutant population is a crucial resource that enriched the sorghum gene pool with novel diversity and a highly valuable tool for the Poaceae family, that will advance plant biology research and crop breeding.


[Design and implementation of a system for transforming the NEMA 2.0 images into DICOM 3.0 images].
This paper introduces the design and implementation of a system which can get the NEMA2.0 image data from the hard disks of the imaging equipments directly,then analyzes and transforms these image data into the DICOM3.0 image data and sends them to the image server. The design has the advantages of reliable image quality, low cost and information.


Checklist of the continental fishes of the state of Chiapas, Mexico, and their distribution.
An updated checklist of the distribution of fishes that inhabit the continental waters of the Mexican state of Chiapas is presented. The state was compartmentalized into 12 hydrological regions for the purpose of understanding the distribution of fish fauna across a state with large physiographic variance. The ichthyofauna of Chiapas is represented by 311 species distributed in two classes, 26 orders, 73 families, and 182 genera, including 12 exotic species. The families with the highest number of species were Cichlidae, Poeciliidae, Sciaenidae, Carangidae, Ariidae, Gobiidae, and Haemulidae. This study attempts to close gaps in knowledge of the distribution of ichthyofauna in the diverse hydrological regions of Chiapas, Mexico.


Structural basis for ubiquitin recognition by a novel domain from human phospholipase A2-activating protein.
Ubiquitin (Ub) is an essential modifier conserved in all eukaryotes from yeast to human. Phospholipase A(2)-activating protein (PLAA), a mammalian homolog of yeast DOA1/UFD3, has been proposed to be able to bind with Ub, which plays important roles in endoplasmic reticulum-associated degradation, vesicle formation, and DNA damage response. We have identified a core domain from the PLAA family ubiquitin-binding region of human PLAA (residues 386-465, namely PFUC) that can bind Ub and elucidated its solution structure and Ub-binding mode by NMR approaches. The PFUC domain possesses equal population of two conformers in solution by cis/trans-isomerization, whereas the two isomers exhibit almost equivalent Ub binding abilities. This domain structure takes a novel fold consisting of four beta-strands and two alpha-helices, and the Ub-binding site on PFUC locates in the surface of alpha2-helix, which is to some extent analogous to those of UBA, CUE, and UIM domains. This study provides structural basis and biochemical information for Ub recognition of the novel PFU domain from a PLAA family protein that may connect ubiquitination and degradation in endoplasmic reticulum-associated degradation.


MFAP4: a candidate biomarker for hepatic and pulmonary fibrosis?
Several comparable mechanisms have been identified for hepatic and pulmonary fibrosis. The human microfibrillar associated glycoprotein 4 (MFAP4), produced by activated myofibroblasts, is a ubiquitous protein playing a potential role in extracellular matrix (ECM) turnover and was recently identified as biomarker for hepatic fibrosis in hepatitis C patients. The current study aimed to evaluate serum levels of MFAP4 in patients with pulmonary fibrosis in order to test its potential as biomarker in clinical practice. A further aim was to determine whether MFAP4 deficiency in mice affects the formation of pulmonary fibrosis in the bleomycin model of lung fibrosis. 91 patients with idiopathic pulmonary fibrosis (IPF), 23 with hypersensitivity pneumonitis (HP) and 31 healthy subjects were studied. In the mouse model, C57BL/6 Mfap4+/+ and Mfap4-/- mice between 6-8 weeks of age were studied. Serum levels of MFAP4 were measured by ELISA in patients and in mice. Surfactant protein D (SP-D) and LDH were measured as comparison biomarkers in patients with pulmonary fibrosis. Morphometric assessment and the Sircol kit were used to determine the amount of collagen in the lung tissue in the mouse model. Serum levels of MFAP4 were not elevated in lung fibrosis - neither in the patients with IPF or HP nor in the animal model. Furthermore no significant correlations with pulmonary function tests of IPF patients could be found for MFAP4. MFAP4 levels were increased in BAL of bleomycin treated mice with pulmonary fibrosis. MFAP4 is not elevated in sera of patients with pulmonary fibrosis or bleomycin treated mice with pulmonary fibrosis. This may be due to different pathogenic mechanisms of liver and lung fibrogenesis. MFAP4 seems to be useful as serum biomarker for hepatic but not for lung fibrosis.


[Antinuclear antibodies and disease specificity].
In this review article, the serum antinuclear autoantibody types which are characteristic especially for rheumatic diseases (ANAs, Anti-ss/ds DNA, Anti-sm, Anti-histone, Anti-RNP, Anti-Ro, Anti-La etc.) were discussed on the basis of their biologic properties, their major role in the diagnosis and monitoring disease activity and response to therapy as well as disease specificity.


Phorbol esters and calcium ionophore can prime murine peritoneal macrophages for tumor cell destruction.
Murine macrophages from sites of inflammation develop toward tumoricidal competence by exposure to a macrophage-activating factor such as interferon-gamma (IFN-gamma). To explore the biochemical transductional events initiated by IFN-gamma, peritoneal macrophages from C57BL/6J mice elicited by various sterile irritants were treated in vitro with two pharmacologic agents that mimic the action of certain second messengers. Phorbol myristate acetate (PMA) and the ionophore A23187 cooperatively reproduced the ability of IFN-gamma to prime macrophages for tumoricidal function. Neither agent alone was able to prime macrophages. The two agents acted on the macrophages, and target susceptibility to kill was not altered by PMA and A23187. Only active phorbol esters, which are known to bind and stimulate protein kinase C, were able to cooperate with A23187 to induce priming. A cell-permeable synthetic diacylglycerol (sn-1,2-dioctanoyl glycerol) could also prime for cytolysis. In the presence of PMA, A23187, and EGTA, addition of Ca++ was sufficient for priming, whereas the addition of Mg++ was much less efficient. Priming by IFN-gamma, however, was not blocked by EGTA. Efflux of 45Ca++ from preloaded cells was significantly increased by A23187 and by IFN-gamma. Quin-2/AM, an intracellular chelator of Ca++, blocked priming by IFN-gamma. In summary, the data suggest that priming of macrophages for tumoricidal function by IFN-gamma involves, at least in part, alterations in protein kinase C and in levels of intracellular Ca++.


Comparison between Hip Internal Rotation Assistive Device and Conventional Radiograph Positioning: An Experimental Study.
Plain anteroposterior radiograph of the hip plays an important role in diagnosing hip pathology. However, one of the most common mistakes is image distortion because the hip is externally rotated due to natural femoral neck anteversion. Thus, the lower extremities should be internally rotated by 15°-20°. The researchers developed a hip internal rotation assistive device and compared it with conventional radiograph positioning. A hip internal rotation assistive device was designed. This study consisted of 20 volunteers without clinical hip pathology. The volunteers were informed to do a hip radiograph twice to compare the efficacy of the developed device with a conventional positioning. The thickness of the lesser trochanter (TLT) was measured and interpreted by an orthopedist and a radiologist. Statistical significance and inter- and intra-observer reliabilities were analysed. According to the orthopaedist's measurement, the mean TLT distance was 4.42 + 3.2mm and 4.97 + 3.16mm for the conventional technique and assistive device, respectively, without statistical significance between both groups (p = 0.05). Consistent with the musculoskeletal radiologist, the mean TLT distance was 4.00 + 2.06mm for the conventional technique and 3.92 + 2.27mm for the assistive device, without statistical significance between both groups (p = 0.56). Intra-observer reliability was 0.900 and 0.898 for the orthopaedist and the radiologist, respectively. Interobserver reliability of the assistive device and conventional technique were 0.800 and 0.588, respectively. The efficacy of the developed device was similar to that of the conventional technique. Inter/intra-observer reliabilities were at a good agreement level in both methods. The developed device would also be useful in clinical applications, especially in decreasing unnecessary radiation exposure of medical personnel.


Comparative Effectiveness of Microdecompression Alone vs Decompression Plus Instrumented Fusion in Lumbar Degenerative Spondylolisthesis.
Conflicting evidence and large practice variation are present in the surgical treatment of degenerative spondylolisthesis. More than 90% of surgical procedures in the United States include instrumented fusion compared with 50% or less in other countries. To evaluate whether the effectiveness of microdecompression alone is noninferior to decompression with instrumented fusion in a real-world setting. This multicenter comparative effectiveness study with a noninferiority design assessed prospective data from the Norwegian Registry for Spine Surgery. From September 19, 2007, to December 21, 2015, 1376 patients at 35 Norwegian orthopedic and neurosurgical departments underwent surgery for lumbar spinal stenosis with degenerative spondylolisthesis without scoliosis. After excluding patients undergoing laminectomy alone, fusion without instrumentation, or surgery in more than 2 levels and those with a former operation at the index level, 794 patients were included in the analyses, regardless of missing or incomplete follow-up data, before propensity score matching. Data were analyzed from March 20 to October 30, 2018. Microdecompression alone or decompression with instrumented fusion. A reduction from baseline of 30% or greater in the Oswestry Disability Index at 12-month follow-up. After propensity score matching, 570 patients (413 female [72%]; mean [SD] age, 64.7 [9.5] years) were included for comparison, with 285 undergoing microdecompression (mean [SD] age, 64.6 [9.8] years; 205 female [72%]) and 285 undergoing decompression with instrumented fusion (mean [SD] age, 64.8 [9.2] years; 208 female [73%]). The proportion of each type of procedure varied between departments. However, changes in outcome scores varied within patients but not between departments. The proportion of patients with improvement in the Oswestry Disability Index of at least 30% was 150 of 219 (68%) in the microdecompression group and 155 of 215 (72%) in the instrumentation group. The 95% CI (-12% to 5%) for the difference of -4% was above the predefined margin of noninferiority (-15%). Microdecompression alone was associated with shorter operation time (mean [SD], 89 [44] vs 180 [65] minutes; P < .001) and shorter hospital stay (mean [SD], 2.5 [2.4] vs 6.4 [3.0] days; P < .001). Among patients with degenerative spondylolisthesis, the clinical effectiveness of microdecompression alone was noninferior to that of decompression with instrumented fusion. Microdecompression alone was also associated with shorter durations of surgery and hospital stay, supporting the suggestion that the less invasive procedure should be considered for most patients.


Proposal for a new tool to evaluate drug interaction cases.
The assessment of causation for a potential drug interaction requires thoughtful consideration of the properties of both the object and precipitant drugs, patient-specific factors, and the possible contribution of other drugs that the patient may be taking. The Naranjo nomogram was designed to evaluate single-drug adverse events, not drug-drug interactions. Several of the questions on the Naranjo nomogram do not apply to potential drug-drug interactions, while others do not specify object or precipitant drug. Nevertheless, it has been inappropriately used to evaluate drug-drug interactions. The Drug Interaction Probability Scale (DIPS) was developed to provide a guide to evaluating drug interaction causation in a specific patient. It is intended to be used to assist practitioners in the assessment of drug interaction-induced adverse outcomes. The DIPS uses a series of questions relating to the potential drug interaction to estimate a probability score. An accurate assessment using the DIPS requires knowledge of the pharmacologic properties of both the object and precipitant drugs. Inadequate knowledge of either the drugs involved or the basic mechanisms of interaction will be a limitation for some users. The DIPS can also serve as a guide in the preparation of articles describing case reports of drug interactions, as well as in the evaluation of published case reports.


Investigating inner-sphere reorganization via secondary kinetic isotope effects in the C-H cleavage reaction catalyzed by soybean lipoxygenase: tunneling in the substrate backbone as well as the transferred hydrogen.
This work describes the application of NMR to the measurement of secondary deuterium (2° (2)H) and carbon-13 ((13)C) kinetic isotope effects (KIEs) at positions 9-13 within the substrate linoleic acid (LA) of soybean lipoxygenase-1. The KIEs have been measured using LA labeled with either protium (11,11-h2-LA) or deuterium (11,11-d2-LA) at the reactive C11 position, which has been previously shown to yield a primary deuterium isotope effect of ca. 80. The conditions of measurement yield the intrinsic 2° (2)H and (13)C KIEs on k(cat)/K(m) directly for 11,11-d2-LA, whereas the values for the 2° (2)H KIEs for 11,11-h2-LA are obtained after correction for a kinetic commitment. The pattern of the resulting 2° (2)H and (13)C isotope effects reveals values that lie far above those predicted from changes in local force constants. Additionally, many of the experimental values cannot be modeled by electronic effects, torsional strain, or the simple inclusion of a tunneling correction to the rate. Although previous studies have shown the importance of extensive tunneling for cleavage of the primary hydrogen at C11 of LA, the present findings can only be interpreted by extending the conclusion of nonclassical behavior to the secondary hydrogens and carbons that flank the position undergoing C-H bond cleavage. A quantum mechanical method introduced by Buhks et al. [J. Phys. Chem. 1981, 85, 3763] to model the inner-sphere reorganization that accompanies electron transfer has been shown to be able to reproduce the scale of the 2° (2)H KIEs.


Closure of the patent ductus arteriosus with the Amplatzer Duct Occluder II: a clinical experience.
The aim of our study was to share our clinical experience on cases with patent ductus arteriosus treated with the Amplatzer Duct Occluder II. Between 2008 and 2012, 26 of 31 patients with patent ductus arteriosus underwent successful transcatheter closure of patent ductus arteriosus using the Amplatzer Duct Occluder II. Mean age was 3.3 years and mean weight was 15.7 kilograms. The presence of a residual shunt, left pulmonary artery or aortic obstruction was explored by administering contrast material during the procedure. The patients were discharged 24 hours after the procedure. The procedure was successful in 26 of 31 patients and failed in five patients. According to the Krichenko classification, 26 patients had type A, one patient had type B and 4 patients had type C ductus. The mean narrowest ductus diameter was 3.2 mm and the mean ductus length was 6.7 mm. Complete angiographic occlusion occurred immediately after the procedure in 22 out of 26 patients in whom the ductus was closed successfully with the Amplatzer Duct Occluder II. Complete occlusion was achieved in the remaining patients with residual shunt one month after the procedure. The procedure was preceded by closure with an Amplatzer Duct Occluder I in two patients and an Amplatzer Vascular Plug I in one patient. Amplatzer Duct Occluder II is highly effective in transcatheter closure of patent ductus arteriosus. We think that an alternative closure device and alternative techniques can be attempted in patients with type C ductus. The success rate could increase with accumulating experience.


Orai calcium release-activated calcium modulator 1 (ORAI1) plays a role in endoplasmic reticulum stress in bovine mammary epithelial cells challenged with physiological levels of ketone bodies.
The Orai calcium release-activated calcium modulator 1 (ORAI1) is a key component of the store-operated Ca2+ entry mechanism regulating cellular Ca2+ balance in nonruminants. Alterations in ORAI1 abundance have been associated with endoplasmic reticulum (ER) stress and changes in lipid metabolism in hepatocytes, an important lipogenic organ in nonruminants. Objectives were to (1) determine abundance of ORAI1 and components of the ER stress response in mammary tissue of ketotic cows, and (2) the potential role of ORAI1 on mammary cell responses to high levels of β-hydroxybutyrate (BHB). Healthy (n = 6, plasma BHB < 0.60 mmol/L) and clinically ketotic (n = 6, plasma BHB > 2.0 mmol/L) Holstein cows (days in milk = 10.13 ± 1.90) were used for mammary gland tissue and blood sample collection. Although milk production (22.5 ± 1.26, 33 ± 1.59, kg of milk/cow per day) and dry matter intake (19.5 ± 1.05, 21.9 ± 0.95, kg/d) were lower in ketotic cows, abundance of ORAI1 protein was greater and was associated with greater mRNA abundance of ER stress proteins (PERK, IRE1, ATF6, and GRP78) and lipogenic genes (FASN, SREBP1, and ACACA). Cellular mechanisms to establish links between BHB and mammary cell responses were evaluated using the immortalized cell line bovine mammary epithelial cells (MAC-T). First, a dose response study was performed with 0, 0.6, 1.2, 1.8, 2.4, or 4.8 mM BHB for 24 h. The mRNA abundance of FASN, SREBP1, and ACACA and lipid droplet formation peaked at 1.2 mM BHB. A subsequent study involved transfecting MAC-T with small interfering Orai 1 (siORAI1) or the ORAI1 inhibitor BTP2 for 24 h followed by a challenge with 1.2 mM BHB for 24 h. Transcription and protein abundance of FASN, SREBP1, ACACA, and ER stress proteins returned to basal levels when ORAI1 was silenced or inhibited. Furthermore, the Ca2+ ionophore ionomycin (raises the intracellular level of Ca2+) also increased abundance of ORAI1, FASN, SREBP1, ACACA, and ER stress proteins. Data suggest that the mammary gland experiences ER stress during ketosis, partly due to the greater supply of BHB originating from ketogenesis in the liver. Intracellular Ca2+ signaling and ORAI1 seem to mediate in part the BHB-induced ER stress in mammary cells.


Binge eating disorder: reliability and validity of a new diagnostic category.
This study examined the reliability and validity of binge eating disorder (BED), which has been proposed for inclusion in the Diagnostic and Statistical Manual of Mental Disorders ([DSM] 4th ed.; American Psychiatric Association, in press). The interrater reliability of the BED diagnosis compared favorably with that of most diagnoses in the revised third edition of the DSM. To assess validity, we compared obese individuals with and without BED and bulimia nervosa patients. BED subjects differed from the non-BED obese group on variables related to dieting and weight histories but did not differ significantly on other important variables, including measures of psychopathology. When compared with bulimia nervosa patients, subjects with BED had significantly less psychopathology and reported significantly less dietary restraint. This study lends some support to the concept of BED but suggests that additional studies of the characteristics of this disorder at different degrees of obesity would be useful.


[Early diagnosis of congenital and infantile strabismus].
Early detection of strabism by the pediatrician is essential for induction of an effective ophthalmologic therapy. Evaluation should not only be done in children with manifest strabism, but also in children prone to develop this disorder like premature-born infants, children with cerebral defects or even children from families with high incidence of strabism.


Variation in size and shape of toxin glands among cane toads from native-range and invasive populations.
If optimal investment in anti-predator defences depends on predation risk, invading new regions (and thus, encountering different predators) may favour shifts in that investment. Cane toads offer an ideal system to test this prediction: expensive anti-predator toxins are stored mainly in parotoid glands whose dimensions are easy to measure, and toad invasions have changed the suites of predators they encounter. Although plasticity may influence parotoid morphology, comparisons between parents and progeny revealed that gland dimensions were highly heritable. That heritability supports the plausibility of an evolved basis to variation in gland dimensions. Measurements of 3779 adult toads show that females have larger glands than males, invasive populations have larger glands than in the native-range, and that parotoid sexual size dimorphism varies strongly among invaded areas. Geographic variation in parotoid morphology may be driven by predation risk to both adult toads and offspring (provisioned with toxins by their mother), with toxins allocated to eggs exacerbating the risk of cannibalism but reducing the risk of interspecific predation. Investment into chemical defences has evolved rapidly during the cane toad's international diaspora, consistent with the hypothesis that organisms flexibly adjust resource allocation to anti-predator tactics in response to novel challenges.


Value of electronic data for model validation and refinement: bacteremia risk in children with fever and neutropenia.
Validating published risk models in a different time and setting can be a labor-intensive process. Data in electronic format provide the potential to test the validity of risk models without labor-intensive chart reviews and data capture. The authors attempted to use readily available electronic data to find appropriate cases and to validate and refine a previously developed risk model for predicting bacteremia in children with cancer who had fever and neutropenia. By applying a largely automated case-finding algorithm to linked, electronic clinical and administrative data systems, the authors identified and acquired data regarding 157 episodes of fever and neutropenia in children with cancer admitted to a children's hospital during an 11-month period in 1997. The authors applied a previously developed and validated risk model for bacteremia to this 1997 cohort by assessing the odds ratios among risk groups. The model assigns encounters with absolute monocyte count of 100 cells or more/mm3 to a low-risk group and encounters with an absolute monocyte count of less than 100 cells/mm3 to intermediate-risk (temperature <39.0 degrees C) or high-risk (> or = 39.0 degrees C) groups. In addition, the authors explored whether the new data would have generated the same model. Univariate and multivariable analyses were performed to determine whether there were additional independent predictors of bacteremia. Recursive partitioning of admission absolute monocyte count and temperature was used to assess whether similar cutpoints would be found. There were 12 episodes of bacteremia (7.6%) among the 157 encounters. The previously developed model correctly predicted increasing rates of bacteremia in this 1997 cohort, ranging from 2.5% in the low-risk group (one episode in a child with an infected central line) to 24% in the high-risk group. The odds ratio for the high-risk versus intermediate-risk group was 4.09 (95% confidence interval 1.05-15.91), comparable to the odds ratio of 3.96 in the previously published derivation cohort (95% confidence interval 1.4-11.1). Multivariate analysis of the new data revealed no independent risk factors for bacteremia other than admission absolute monocyte count and temperature. Recursive partitioning of absolute monocyte count and temperature generated risk categories that were somewhat different from those of the original model. The new data yielded three categories: low risk (temperature < or = 39.5 degrees C and absolute monocyte count >10/mm3), intermediate risk (temperature < or = 39.5 degrees C and absolute monocyte count < or = 10/mm3), and high risk (temperature >39.5 degrees C). Existing electronic data provide an efficient means for case-finding and model validation and refinement. The previously developed bacteremia model had good but not optimal predictive performance in the new data set. Admission absolute monocyte count and temperature remain significant risk factors for bacteremia. Redefining the risk categories, including a much lower cutpoint for admission absolute monocyte count, improved the model's discrimination, which suggests that predictive models need periodic updating.


Polymer properties of softwood organosolv lignins produced in two different reactor systems.
Lignin, the second most abundant biopolymer on earth and with a predominantly aromatic structure, has the potential to be a raw material for valuable chemicals and other bio-based chemicals. In industry, lignin is underutilized by being used mostly as a fuel for producing thermal energy. Valorization of lignin requires knowledge of the structure and different linkages in the isolated lignin, making the study of structure of lignin important. In this article, lignin samples isolated from two types of reactors (autoclave reactor and displacement reactor) were analyzed by FT-IR, size exclusion chromatography, thermogravimetric analysis (TGA), and Py-GC-MS. The average molecular mass of the organosolv lignins isolated from the autoclave reactor decreased at higher severities, and FT-IR showed an increase in free phenolic content with increasing severity. Except for molecular mass and molecular mass dispersity, there were only minor differences between lignins isolated from the autoclave reactor and lignins isolated from the displacement reactor. Carbohydrate analysis, Py-GC-MS and TGA showed that the lignin isolated using either of the reactor systems is of high purity, suggesting that organosolv lignin is a good candidate for valorization.


In vivo efficacy of antimicrobe-impregnated saline-filled silicone implants.
Bacterial colonization of mammary implants is a prelude to clinical infection and has been implicated in the etiology of capsular contracture. Antimicrobial impregnation of a variety of medical devices with the combination of minocycline and rifampin has recently emerged as a potentially effective method for preventing device colonization and device-related infection. The objective of this animal study was to examine in vivo the antimicrobial efficacy of minocycline/rifampin-impregnated, saline-filled silicone implants. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously placed implants was used. A total of 48 saline-filled silicone implants (24 antimicrobe-impregnated and 24 control unimpregnated implants) were suspended in a 106 colony-forming units/ml bacterial suspension of S. aureus for 30 minutes at room temperature, allowed to dry for 60 minutes, and then implanted subcutaneously in the back of 12 rabbits (two antimicrobe-impregnated and two control implants were placed in each rabbit). Rabbits were monitored daily, then killed either at 2 weeks (10 rabbits) or at 4 weeks (two rabbits) and cultured. The antimicrobe-impregnated implants were 12 times less likely to be colonized than control unimpregnated implants (two of 24 versus 23 of 24; p < 0.001), and they were a significantly less likely cause of implant-related infection (0 of 24 versus 22 of 24; p < 0.001) and implant-related abscess (0 of 24 versus 21 of 24; p < 0.001) than control implants. The minocycline/rifampin-impregnated implants routinely demonstrated zones of inhibition against S. aureus at the time of explantation. These results indicate that minocycline/rifampin-impregnated implants can significantly decrease the rate of bacterial colonization, implant-related infection, and implant-related abscess. Antimicrobe-impregnated implants also have the potential of reducing the likelihood of capsular contracture.


The influence of health-risk perception and distress on reactions to low-level chemical exposure.
The general aim of the current study was to investigate how perceived health risk of a chemical exposure and self-reported distress are related to perceived odor intensity and odor valence, symptoms, cognitive performance over time as well as reactions to blank exposure. Based on ratings of general distress, 20 participants constituted a relatively low distress group, and 20 other participants a relatively high distress group. Health risk perception was manipulated by providing positively and negatively biased information regarding n-butanol. Participants made repeated ratings of intensity, valence and symptoms and performed cognitive tasks while exposed to 4.7 ppm n-butanol for 60 min (first 10 min were blank exposure) inside an exposure chamber. Ratings by the positive and negative bias groups suggest that the manipulation influenced perceived health risk of the exposure. The high distress group did not habituate to the exposure in terms of intensity when receiving negative information, but did so when receiving positive information. The high distress group, compared with the low distress group, rated the exposure as significantly more unpleasant, reported greater symptoms and performed worse on a cognitively demanding task over time. The positive bias group and high distress group rated blank exposure as more intense. The main findings suggest that relatively distressed individuals are negatively affected by exposures to a greater degree than non-distressed.


Diagnosis of paroxysmal nocturnal hemoglobinuria in peripheral blood and bone marrow with six-color flow cytometry.
Identification of paroxysmal nocturnal hemoglobinuria (PNH) by detecting a glycophosphatidylinositol-anchored defect by flow cytometry is presently the standard method of choice for diagnosing PNH. However, the selection of suitable markers will be critical and significantly affect the determination and quantification of PNH clones in various cell lineages. In this study, we investigated the performance of various immunophenotypic markers including CD59, GPHA (a clustered antigen, CD235a), CD33, CD15 and fluorescent aerolysin (FLAER) combined with CD16, CD24 and CD14 in a PNH panel using six-color flow cytometry. The results strongly indicate that these markers can collectively and effectively identify and quantify PNH clones in erythrocyte, granulocyte and monocyte populations derived from peripheral blood and bone marrow (BM). A sensitivity threshold as low as 0.01% in identifying PNH clones in erythrocyte and granulocyte populations from peripheral blood is achieved by this panel in a series dilution assay. In addition, a direct side-by-side comparison between BM and peripheral blood from the same patients suggests that the FLAER PNH test is capable of identifying to PNH clones in BM specimens. The data support the premise that a six-color flow cytometry PNH panel using the combination of CD59, CD235a, CD33, CD15, FLAER, CD16, CD24 and CD14 can enhance and improve the current methods used in diagnosis and management of PNH by specifically identifying PNH clones in the erythrocyte, granulocyte and monocyte population.


Knowledge of occupational exposure to HIV: a cross sectional study of healthcare workers in Tumbi and Dodoma hospitals, Tanzania.
Insufficient knowledge on blood-borne pathogens has been identified as a factor that influences occupational exposure to needle stick and sharps injuries. The objective of this study was to assess healthcare workers' knowledge on occupational exposure to HIV. A cross sectional survey was conducted at Tumbi designated regional hospital and Dodoma regional hospital, Tanzania in February 2012. A self-administered questionnaire was used to capture information on knowledge of occupational exposure to HIV infection. A total of 401 healthcare workers responded to a self-administered questionnaire. High proportion of healthcare workers (96.3%) understood that they are at risk of occupational exposure to HIV. The majority of healthcare workers trained on post exposure prophylaxis procedure and use of personal protective equipment were clinicians (87.1% and 71.4% respectively) and nurses (81.8% and 74.6% respectively). Over a quarter of the healthcare workers were not aware of whom to contact in the event of occupational exposure. One third of healthcare workers did not have comprehensive knowledge on causes of occupational HIV transmission and did not know when post exposure prophylaxis is indicated. Healthcare workers not trained on the use of person protective equipment were less likely to have comprehensive knowledge on occupational exposure to HIV (OR = 0.5; 95% CI 0.3 - 0.9). Knowledge on causes of occupational exposure varied with the cadre of healthcare workers. Nurses were more likely to have comprehensive knowledge on occupational exposure to HIV than non-clinical staff (OR = 2.6; 95% CI 1.5 - 4.5). A substantial proportion of studied healthcare workers had little knowledge on occupational exposure to HIV and was not aware of a contact person in the event of occupational exposure to HIV. Training on post exposure prophylaxis and infection prevention and control including the use of person protective equipment provided to nurses and clinicians should be extended to other clinical and non-clinical hospital staff.


Virgin Olive Oil as Frying Oil.
Frying is one of the oldest cooking procedures and is still among the most popular ones for food preparation. Due to their unique sensory characteristics, fried foods are consumed often and with pleasure. During frying, part of the oil is absorbed by the food, thereby becoming part of our diet; most interestingly, in the Mediterranean area approximately 50% of total fat intake is provided by cooking fats. Olive oil is the key lipid component of the Mediterranean diet, the health-promoting effects of which have been largely attributed to olive oil intake. Olive oil is unique among vegetable oils due to its desirable lipid profile and some of its minor components. Scientific evidence now indicates that during frying olive oil behavior is usually equal or superior to that of refined vegetable oils. Herein, an overview of virgin olive oil performance under frying is given, with special reference to the fate of olive oil microconstituents. The compositional changes of foods fried in olive oil are also reviewed and discussed in detail.


Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors.
Development of an anti-SARS-CoV-2 therapeutic is hindered by the lack of physiologically relevant model systems that can recapitulate host-viral interactions in human cell types, specifically the epithelium of the lung. Here, we compare induced pluripotent stem cell (iPSC)-derived alveolar and airway epithelial cells to primary lung epithelial cell controls, focusing on expression levels of genes relevant for COVID-19 disease modeling. iPSC-derived alveolar epithelial type II-like cells (iAT2s) and iPSC-derived airway epithelial lineages express key transcripts associated with lung identity in the majority of cells produced in culture. They express ACE2 and TMPRSS2, transcripts encoding essential host factors required for SARS-CoV-2 infection, in a minor subset of each cell sub-lineage, similar to frequencies observed in primary cells. In order to prepare human culture systems that are amenable to modeling viral infection of both the proximal and distal lung epithelium, we adapt iPSC-derived alveolar and airway epithelial cells to two-dimensional air-liquid interface cultures. These engineered human lung cell systems represent sharable, physiologically relevant platforms for SARS-CoV-2 infection modeling and may therefore expedite the development of an effective pharmacologic intervention for COVID-19.


Temperature and viscosity dependence of the electron-transfer reaction between plastocyanin and cytochrome c labeled with a ruthenium(II) bipyridine complex.
The temperature and viscosity dependence of the photo-induced electron-transfer reaction between plastocyanin and cytochrome c labeled at Lys13 with Ru(4,4'-dicarboxybipyridine)(bipyridine)(2+)2 have been investigated. In these studies, a short pulse of 450 nm light was used to excite the ruthenium complex which was oxidatively quenched by the iron center of cytochrome c. The resulting Fe(II) cytochrome c was then rapidly reoxidized by plastocyanin. The reactions were investigated over a temperature range of 3.5 to 37 degrees C under low ionic strength conditions such that protein/protein complex formation was favored. The enthalpy of activation was 7 kcal mol-1 and the entropy of activation was -20 cal mol-1 K-1. Increasing the viscosity by the addition of sucrose up to 70% resulted in a 4-fold decrease in the rate constant for electron transfer. The overall results suggest a rate-limiting step that involves either dissociation of the dominant protein/protein complex or surface diffusion of the associated proteins.


DanceIt: Music-Inspired Dancing Video Synthesis.
Close your eyes and listen to music, one can easily imagine an actor dancing rhythmically along with the music. These dance movements are usually made up of dance movements you have seen before. In this paper, we propose to reproduce such an inherent capability of the human-being within a computer vision system. The proposed system consists of three modules. To explore the relationship between music and dance movements, we propose a cross-modal alignment module that focuses on dancing video clips, accompanied by pre-designed music, to learn a system that can judge the consistency between the visual features of pose sequences and the acoustic features of music. The learned model is then used in the imagination module to select a pose sequence for the given music. Such pose sequence selected from the music, however, is usually discontinuous. To solve this problem, in the spatial-temporal alignment module we develop a spatial alignment algorithm based on the tendency and periodicity of dance movements to predict dance movements between discontinuous fragments. In addition, the selected pose sequence is often misaligned with the music beat. To solve this problem, we further develop a temporal alignment algorithm to align the rhythm of music and dance. Finally, the processed pose sequence is used to synthesize realistic dancing videos in the imagination module. The generated dancing videos match the content and rhythm of the music. Experimental results and subjective evaluations show that the proposed approach can perform the function of generating promising dancing videos by inputting music.


Temperature effects on gametophyte life-history traits and geographic distribution of two cryptic kelp species.
A major determinant of the geographic distribution of a species is expected to be its physiological response to changing abiotic variables over its range. The range of a species often corresponds to the geographic extent of temperature regimes the organism can physiologically tolerate. Many species have very distinct life history stages that may exhibit different responses to environmental factors. In this study we emphasized the critical role of the haploid microscopic stage (gametophyte) of the life cycle to explain the difference of edge distribution of two related kelp species. Lessonia nigrescens was recently identified as two cryptic species occurring in parapatry along the Chilean coast: one located north and the other south of a biogeographic boundary at latitude 29-30°S. Six life history traits from microscopic stages were identified and estimated under five treatments of temperature in eight locations distributed along the Chilean coast in order to (1) estimate the role of temperature in the present distribution of the two cryptic L. nigrescens species, (2) compare marginal populations to central populations of the two cryptic species. In addition, we created a periodic matrix model to estimate the population growth rate (λ) at the five temperature treatments. Differential tolerance to temperature was demonstrated between the two species, with the gametophytes of the Northern species being more tolerant to higher temperatures than gametophytes from the south. Second, the two species exhibited different life history strategies with a shorter haploid phase in the Northern species contrasted with considerable vegetative growth in the Southern species haploid stage. These results provide strong ecological evidence for the differentiation process of the two cryptic species and show local adaptation of the life cycle at the range limits of the distribution. Ecological and evolutionary implications of these findings are discussed.


Fibrosarcoma affecting the mammary gland of a cow.
A highly malignant fibrosarcoma which arose in or close to the mammary gland of a 12 year old Ayrshire cow, with metastases in local lymph nodes, lungs, liver, kidney and adrenal glands has been described. The tumors were densely cellular and consisted of interweaving bands of fusiform cells with a high mitotic index. Infiltration of normal tissues and invasion of blood vessels were characteristic features. Ultrastructural study of the cells revealed mesenchymal cells with abundance of rough endoplasmic reticulum and cytoplasmic vesicles and they were closely invested with collagen fibers.


The nature and correlates of avoidance in obsessive-compulsive disorder.
Avoidance in obsessive-compulsive disorder (OCD) has been neglected by research. This study aimed (i) to collect information on the nature and frequency of avoidance in people with OCD and ascertain the types of obsessions related to avoidance; (ii) compare OCD individuals with and without avoidance, and (iii) determine predictors of avoidance in people with OCD. A total of 124 OCD adults underwent a comprehensive assessment. Participants were asked whether they engaged in any avoidance behaviour because of their OCD, and the nature and number of instances of such avoidance were recorded. The instances of avoidance were grouped according to the type of obsession and compulsion that they were related to. A total of 74 (59.7%) participants reported OCD-related avoidance. Avoidance was most commonly related to contamination obsessions. Almost 80% of all contamination obsessions and more than 50% of all aggressive obsessions were associated with avoidance, and contamination obsessions were significantly more common among the participants with avoidance. In contrast, very few obsessions about a need to collect and keep objects and obsessions about a need for ordering, arranging and doing things right or in an exact way were associated with avoidance; these types of obsessions were also significantly more common among the participants without avoidance. The strongest predictor of avoidance was the presence of contamination obsessions. Participants with avoidance had a significantly more severe OCD than those without avoidance. Avoidance is common in OCD, and it is particularly frequently associated with contamination obsessions. There is a weak link between avoidance and hoarding and between avoidance and ordering/arranging/symmetry obsessions and compulsions. These results, along with the finding that OCD with avoidance is a more severe illness, have implications for the future diagnostic criteria, description, subtyping and treatment of OCD and for its relationship with other anxiety disorders.


Paleolithic Paint.
Discovery of hematite and kaolinite in excavations of late paleolithic occupation sites at Les Eyzies (Dordogne), France, raises anew the question of the nature of the paint used by paleolithic people. Hematite as a pigment source is widely documented, but the presence of kaolinite imported into prehistoric sites poses problems. The suggestion is made that white clay might have been used as an "extender pigment" to mix with colors such as that derived from hematite.


Molecular-based isothermal tests for field diagnosis of malaria and their potential contribution to malaria elimination.
In countries where malaria transmission has decreased substantially, thanks to the scale-up of control interventions, malaria elimination may be feasible. Nevertheless, this goal requires new strategies such as the active detection and treatment of infected individuals. As the detection threshold for the currently used diagnostic methods is 100 parasites/μL, most low-density, asymptomatic infections able to maintain transmission cannot be detected. Identifying them by molecular methods such as PCR is a possible option but the field deployment of these tests is problematic. Isothermal amplification of nucleic acids (at a constant temperature) offers the opportunity of addressing some of the challenges related to the field deployment of molecular diagnostic methods. One of the novel isothermal amplification methods for which a substantial amount of work has been done is the loop-mediated isothermal amplification (LAMP) assay. The present review describes LAMP and several other isothermal nucleic acid amplification methods, such as thermophilic helicase-dependent amplification, strand displacement amplification, recombinase polymerase amplification and nucleic acid sequence-based amplification, and explores their potential use as high-throughput, field-based molecular tests for malaria diagnosis.


Preparation, Characterization, and Activity of Pd/PSS-Modified Membranes in the Low Temperature Dry Reforming of Methane with and without Addition of Extra Steam.
The external surface of a commercial porous stainless steel (PSS) was modified by either oxidation in air at varying temperatures (600, 700, and 800 °C) or coating with different oxides (SiO2, Al2O3, and ZrO2). Among them, PSS-ZrO2 appears as the most suitable carrier for the synthesis of the Pd membrane. A composite Pd membrane supported on the PSS-ZrO2 substrate was prepared by the electroless plating deposition method. Supported Ru catalysts were first evaluated for the low-temperature methane dry reforming (DRM) reaction in a continuous flow reactor (CR). Ru/ZrO2-La2O3 catalyst was found to be active and stable, so it was used in a membrane reactor (MR), which enhances the methane conversions above the equilibrium values. The influence of adding H2O to the feed of DRM was investigated over a Ru/ZrO2-La2O3 catalyst in the MR. Activity results are compared with those measured in a CR. The addition of H2O into the feed favors other reactions such as Water-Gas Shift (RWGS) and Steam Reforming (SR), which occur together with DRM, resulting in a dramatic decrease of CO2 conversion and CO production, but a marked increase of H2 yield.


Health supervision in the management of children and adolescents with IBD: NASPGHAN recommendations.
Ulcerative colitis (UC) and Crohn disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic inflammatory disorders that can affect the gastrointestinal tract of children and adults. Like other autoimmune processes, the cause(s) of these disorders remain unknown but likely involves some interplay between genetic vulnerability and environmental factors. Children, in particular with UC or CD, can present to their primary care providers with similar symptoms, including abdominal pain, diarrhea, weight loss, and bloody stool. Although UC and CD are more predominant in adults, epidemiologic studies have demonstrated that a significant percentage of these patients were diagnosed during childhood. The chronic nature of the inflammatory process observed in these children and the waxing and waning nature of their clinical symptoms can be especially disruptive to their physical, social, and academic development. As such, physicians caring for children must consider these diseases when evaluating patients with compatible symptoms. Recent research efforts have made available a variety of more specific and effective pharmacologic agents and improved endoscopic and radiologic assessment tools to assist clinicians in the diagnosis and interval assessment of their patients with IBD; however, as the level of complexity of these interventions has increased, so too has the need for practitioners to become familiar with a wider array of treatments and the risks and benefits of particular diagnostic testing. Nonetheless, in most cases, and especially when frequent visits to subspecialty referral centers are not geographically feasible, primary care providers can be active participants in the management of their pediatric patients with IBD. The goal of this article is to educate and assist pediatricians and adult gastroenterology physicians caring for children with IBD, and in doing so, help to develop more collaborative care plans between primary care and subspecialty providers.


New SNPs for population genetic analysis reveal possible cryptic speciation of eastern Australian sea mullet (Mugil cephalus).
Sustainable management of sea mullet (Mugil cephalus) fisheries needs to account for recent observations of regional-scale differentiation. Population genetic analysis is sought to assess the situation of this ecologically and economically important fish species in eastern Australian waters. Here, we report (i) new population genetic markers [single nucleotide polymorphisms (SNPs) and potential microsatellites], (ii) first estimates of spatial genetic differentiation and (iii) prospective power tests for designing more comprehensive studies. Six DNA samples from three sampling regions (North Queensland, South Queensland and central New South Wales) on the eastern coast of Australia were used to prepare restriction site associated DNA (RAD) tag libraries from genomic DNA digested with EcoRI and MseI. A pooled sample of regional RAD tag libraries was sequenced using the Roche GS-FLX Titanium platform. A total of 172,837 raw reads (17.4 Mbp) were retrieved, 95,500 of which were used to discover 1267 SNPs and 1417 microsatellites. A subset of 161 SNPs was validated based on 63 additional DNA samples genotyped using the Sequenom MassArray (iPLEX Gold chemistry). Altogether 92 SNPs (57%) were confirmed, with 40% of these marking fixed variants between northern and southern sampling regions. Our preliminary findings indicate a multispecies fishery stock of M. cephalus in eastern Australian waters, but suggest that strong genetic differentiation occurs north of major fishing grounds. Low potential differentiation within major fishing grounds (e.g. FST = 0.0025) can be resolved with a likely power ≥67% by using standard sample sizes of 50 and validated subsets of available markers.


SOX12 and NRSN2 are candidate genes for 20p13 subtelomeric deletions associated with developmental delay.
20p13 telomeric/subtelomeric deletions are clinically significant but are currently under-investigated. So far only five molecularly delineated cases have been reported in literature and no candidate genes have been sufficiently implicated. Here, we present six new deletion cases identified by chromosomal microarray analysis (CMA). We also review 32 cases combined from literature and databases. We found that most 20p13 deletion patients exhibit significant developmental delay. Dysmorphic features are common but a consistent pattern was not recognized. Reduced cognitive ability was frequent. Based on pathogenic deletions delineated in this study, we mapped the smallest overlapping region and identified two nervous system expressing genes (SOX12 and NRSN2) as candidate genes that may be involved in the developmental defects in 20p13 microdeletion.


[Involvement of Syk in pathology of systemic autoimmune disease].
Biological products have proven its high efficacy on autoimmune disease such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Meanwhile, small molecular drugs have attracted attention over the years because of its availability of oral administration and cost effectiveness. Spleen tyrosine kinase (Syk) is a 72 kDa protein tyrosine kinase widely expressed on cells that are involved in the immune system and inflammation such as B cells, T cells, macrophages and synovial fibroblast. Syk is involved in intracellular signaling of the multi-chain immune receptors, including B cell receptor (BCR), ζchain of T-cell receptor (TCR), FcR and integrins, which contains the immune-receptor tyrosine-based activation motif (ITAM). Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP). Moreover, Syk blockade prevented the development of skin and kidney lesions in lupus-prone mice, however the mechanism of action is unclear. We have revealed that Syk-mediated BCR-signaling is prerequisite for optimal induction of toll-like receptor (TLR)-9, thereby allowing efficient propagation of CD40- and TLR9- signaling in human B cells. These results indicate that inhibition of Syk have a potential to regulate B-cell mediated inflammatory diseases such as SLE. We here document the in vitro and in vivo effects of a Syk inhibitor for the treatment of autoimmune diseases, mainly in RA and SLE.


Independent complexity patterns in single neuron activity induced by static magnetic field.
We applied a combination of fractal analysis and Independent Component Analysis (ICA) method to detect the sources of fractal complexity in snail Br neuron activity induced by static magnetic field of 2.7 mT. The fractal complexity of Br neuron activity was analyzed before (Control), during (MF), and after (AMF) exposure to the static magnetic field in six experimental animals. We estimated the fractal dimension (FD) of electrophysiological signals using Higuchi's algorithm, and empirical FD distributions. By using the Principal Component Analysis (PCA) and FastICA algorithm we determined the number of components, and defined the statistically independent components (ICs) in the fractal complexity of signal waveforms. We have isolated two independent components of the empirical FD distributions for each of three groups of data by using FastICA algorithm. ICs represent the sources of fractal waveforms complexity of Br neuron activity in particular experimental conditions. Our main results have shown that there could be two opposite intrinsic mechanisms in single snail Br neuron response to static magnetic field stimulation. We named identified ICs that correspond to those mechanisms - the component of plasticity and the component of elasticity. We have shown that combination of fractal analysis with ICA method could be very useful for the decomposition and identification of the sources of fractal complexity of bursting neuronal activity waveforms.


Misperceptions of speed are accounted for by the responses of neurons in macaque cortical area MT.
In humans, the perceived speed of random dot patterns (RDP) moving within small apertures is faster than that of RDPs moving within larger apertures at the same physical speed. To investigate the neural basis of this illusion, we recorded the responses of direction- and speed-selective neurons in the middle temporal area (MT) of macaque monkeys to stimuli varying in size and speed. Our results show that the preferred speed of MT neurons is slower for smaller stimuli. This effect was larger for neurons preferring faster speeds, matching our psychophysical observation in human subjects that the magnitude of the misperception is larger at higher stimulus speeds. Our physiological data indicate that, across a population of speed-tuned neurons in MT, decreasing the size of a stimulus would shift the activity profile to neurons tuned for higher speeds. Modeling a labeled-line readout of this shifted profile, we show an increased apparent speed, in line with the psychophysical observations. This link strengthens the evidence for a causal role of area MT in speed perception. The systematic shift in tuning curves of single neurons with stimulus size might reflect a general mechanism for feature-mismatch illusions in visual perception.


Intrathecal Baclofen Injection to Avoid Withdrawal in a Multiple Sclerosis Patient Undergoing Lumbar Spine Surgery: A Case Report.
Spasticity of spinal or cerebral origin is frequently treated with baclofen. Treatment interruption initially results in rebound spasticity; life-threatening withdrawal symptoms may follow. Severe rebound spasticity of leg muscles occurred in a multiple sclerosis patient after a 10-hour long perioperative pause of oral baclofen intake. In a subsequent spine surgery, recurrence was prevented by substituting a cumulative 12-hour oral baclofen dose with an intraoperative intrathecal injection. Administration of intrathecal baclofen during prolonged surgery in patients dependent on oral baclofen may improve patient comfort and prevent early withdrawal symptoms. The most optimal conversion ratio from oral to intrathecal baclofen is still undetermined.


Interaction of the heterozygous nude gene with the asplenia trait in mammary tumorigenesis.
The BALB/c mouse strain has been shown to contain endogenous mouse mammary tumor virus (MMTV) proviral sequences. However, no exogenous MMTV particles have been detected in their tissues. Female BALB/c mice from our colonies exhibit a very low incidence of spontaneous mammary tumors (SMT); less than 1% at up to 20 mo of age. Immunodeficient BALB/c mice heterozygous for the nude gene (nu/+, +/+), for the dominant hemimelia gene associated with asplenia (+/+, Dh/+), or for both traits (nu/+, Dh/+) have been examined for SMT incidence and the presence of MMTV proviruses. Based on restriction digestion with Eco RI, Bam HI, and Pst I, the immunodeficient mice have an MMTV provirus copy number and organization identical to the BALB/cCrgl strain. This MMTV DNA pattern is distinct from the MMTV proviruses in C3H/He, C57BL/6J and CBA/CaJ mice, which were parental strains of the immunodeficient mutants. Normal female BALB/c or BALB/c heterozygous for the asplenic trait do not develop significant numbers of SMT at up to 19 mo of age. In contrast, an incidence of 23.8% and 57.7% SMT was observed in BALB/c nu/+ heterozygotes, and in BALB/c nu/+, Dh/+ heterozygotes, respectively. These results indicate that agenesis of the spleen, concomitant with the presence of the heterozygous nude gene, contribute to a high incidence of SMT in the low-SMT BALB/c mouse strain.


The Burden of HIV/AIDS in Ethiopia from 1990 to 2016: Evidence from the Global Burden of Diseases 2016 Study.
The burden of HIV/AIDS in Ethiopia has not been comprehensively assessed over the last two decades. In this study, we used the 2016 Global Burden of Diseases, Injuries and Risk factors (GBD) data to analyze the incidence, prevalence, mortality and Disability-adjusted Life Years Lost (DALY) rates of Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS) in Ethiopia over the last 26 years. The GBD 2016 used a wide range of data source for Ethiopia such as verbal autopsy (VA), surveys, reports of the Federal Ministry of Health and the United Nations (UN) and published scientific articles. The modified United Nations Programme on HIV/AIDS (UNAIDS) Spectrum model was used to estimate the incidence and mortality rates for HIV/AIDS. In 2016, an estimated 36,990 new HIV infections (95% uncertainty interval [UI]: 8775-80262), 670,906 prevalent HIV cases (95% UI: 568,268-798,970) and 19,999 HIV deaths (95% UI: 16426-24412) occurred in Ethiopia. The HIV/AIDS incidence rate peaked in 1995 and declined by 6.3% annually for both sexes with a total reduction of 77% between 1990 and 2016. The annualized HIV/AIDS mortality rate reduction during 1990 to 2016 for both sexes was 0.4%. Ethiopia has achieved the 50% reduction of the incidence rate of HIV/AIDS based on the Millennium Development Goals (MDGs) target. However, the decline in HIV/AIDS mortality rate has been comparatively slow. The country should strengthen the HIV/AIDS detection and treatment programs at community level to achieve its targets during the Sustainable Development Program (SDGs)-era.


One-person and two-person conceptions of attachment and their implications for psychoanalytic thought.
There has been increasing interest among analysts in the possibilities of enriching psychoanalytic thought through fuller incorporation of attachment theory and research. This paper offers a clinical illustration of the ways in which attention to an attachment perspective can lead to novel and useful ways of addressing the patient's issues. It also presents a number of cautions that it is necessary to be alert to if attachment thinking is to achieve its full potential in advancing psychoanalytic thought and practice. Conceptions of attachment and approaches to its study and clinical use actually vary quite substantially. Some are more one-person, static, and categorical. Others are more two-person, dynamic, and focused on the process whereby attachment patterns develop and are maintained over time. This paper explores the distinction between these two versions of attachment theory and research with two aims in mind - first, to refine our understanding of the potential role that attachment thinking can play in advancing the psychoanalytic paradigm; second, to utilize the insights achieved through examining the attachment paradigm to consider some broader issues in the construction of psychoanalytic theory more generally and its relational variant in particular.


Mercury and the risk of coronary heart disease in men.
A high dietary intake of mercury from consumption of fish has been hypothesized to increase the risk of coronary heart disease. Using a nested case-control design, we investigated the association between mercury levels in toenails and the risk of coronary heart disease among male health professionals with no previous history of cardiovascular disease or cancer who were 40 to 75 years of age in 1986. Toenail clippings were collected in 1987 from 33,737 cohort members, and during five years of follow-up, we documented 470 cases of coronary heart disease (coronary-artery surgery, nonfatal myocardial infarction, and fatal coronary heart disease). Each patient was matched according to age and smoking status with a randomly selected control subject. The mercury level was significantly correlated with fish consumption (Spearman r=0.42, P<0.001), and the mean mercury level was higher in dentists than in nondentists (mean, 0.91 and 0.45 microg per gram, respectively; P<0.001). After age, smoking, and other risk factors for coronary heart disease had been controlled for, the mercury level was not significantly associated with the risk of coronary heart disease. When the highest and lowest quintiles of mercury level were compared, the relative risk of coronary heart disease was 0.97 in the highest level (95 percent confidence interval, 0.63 to 1.50; P value for trend=0.78). Adjustment for intake of n-3 fatty acids from fish did not appreciably change these results. Our findings do not support an association between total mercury exposure and the risk of coronary heart disease, but a weak relation cannot be ruled out.


Prediction of maintenance oral theophylline dosage using single oral doses in patients with obstructive airways disease.
This study was designed to test whether single oral doses of theophylline, rather than the specified single intravenous infusions, could be used with a nomogram designed to predict the maintenance oral dose necessary to establish plasma theophylline concentrations of 10 micrograms ml (Koup et al., 1979) in patients with obstructive airways disease. A test dose of theophylline (5 mg kg) was administered on two separate occasions as an oral elixir and as an intravenous infusion. Exactly 6 h after each test dose, plasma theophylline concentration was measured, and the result used to predict daily maintenance dose requirements. During subsequent oral administration, a sustained-release preparation was given in equally divided 12-hourly doses, and 'steady-state' concentrations were measured at trough. Nineteen patients completed the study, and on doses ranging from 4.2 to 21.1 mg kg-1 day-1, trough concentrations of 5.4 to 15.8 micrograms ml (mean 10.0 +/- 0.7 micrograms ml) were achieved. No significant differences were noted between the dose predictions made following either the oral or the intravenous test doses, and the predictive accuracy using the oral route was not compromised. This would suggest that the test dose of theophylline may be administered orally, instead of intravenously, with this nomogram without reducing its efficiency.


A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation.
A randomized double-blind, active controlled, parallel group, multi-center phase II clinical trial was conducted to evaluate the efficacy of reduced-nicotine cigarettes as a novel smoking cessation treatment (under Investigational Device Exemption 69,185). The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking. Treatment consisted of Quest brand of cigarettes (Quest 1, 2, and 3), which respectively deliver 0.59+/-0.06, 0.3+/-0.05, and less than 0.05 mg nicotine, either alone or in combination with nicotine replacement therapy (NRT). The primary endpoint was 4 weeks of continuous abstinence (Weeks 7-10), with additional follow-up at 3 and 6 months. Adult men and women smokers (N = 346), motivated to quit, were randomized to one of three treatment groups: Quest plus NRT (NRT pretreatment 2 weeks before, and NRT after the quit date), Quest plus placebo patch, or active control plus NRT (conventional cigarette, followed by NRT after quit date). Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%). Quest plus placebo patch yielded an abstinence rate similar to that of the active control plus NRT (16.4% vs. 21.9%). No serious adverse events were attributable to the investigational product. Quest plus NRT offers promise as a new smoking cessation treatment.


Evaluation of the safety of ramucirumab in Japanese patients with advanced gastric cancer.
As a result of the RAINBOW trial, ramucirumab plus paclitaxel was established as a second-line treatment of advanced gastric cancer. Regarding the safety of ramucirumab plus paclitaxel in the Japanese, a subgroup analysis of the RAINBOW trial was conducted. The incidence of neutropenia was higher in Japanese patients. However, information is lacking concerning the safety of ramucirumab after marketing in Japanese patients. Therefore, the aim of this study was to evaluate the safety of ramucirumab in Japanese patients with advanced gastric cancer. The inclusion criteria were patients diagnosed with advanced gastric cancer who had commenced treatment with ramucirumab plus paclitaxel or paclitaxel only at Ogaki Municipal Hospital (Gifu, Japan) between January 2015 and December 2016. There were 26 patients in the ramucirumab plus paclitaxel group and 22 patients in the paclitaxel only group. Treatment-related adverse events were documented in 100.0% of the patients in the ramucirumab plus paclitaxel group (Grade 3-4, 73.1%) and 90.9 % of the patients in the paclitaxel only group (Grade 3-4, 45.5 %). The most frequently observed adverse event in both treatment groups was anemia. The second common adverse event was neutropenia. The incidence of neutropenia of Grade ≥3 was significantly higher in the ramucirumab plus paclitaxel group than in the paclitaxel only group. In conclusion, the incidence of neutropenia is high. However, we believe that ramucirumab plus paclitaxel can be safely administered.


[Fetal echocardiography in fetal ovarian cysts].
The aim of the study was to evaluate the outcome of fetuses with ovarian cysts in relation to fetal echocardiography. In the Department for Diagnosis and Prophylaxis of Birth Defects at the Polish Mother's Memorial Hospital in Lodz fetal echocardiography was performed in 21 fetuses with ovarian cysts between the years 1995-2006. In 18 out of 21 (86%) fetuses we have found normal heart anatomy (NHA) and in 3 fetuses congenital heart defect (CHD). In 7 out of 18 (39%) fetuses with NHA there were functional anomalies, including 5 fetuses with hypertrophy Four neonates with hypertrophy required surgical procedures after the delivery. Prenatal hypertrophy was not observed in case of only one neonate which was operated after the delivery. 1. Fetal echocardiography studies were very often abnormal in fetus with ovarian cysts (mainly as functional anomalies). 2. Functional anomalies detected in fetal echocardiography more often resulted in surgical procedures after the birth, whereas normal heart study was more often connected with spontaneous regression of ovarian cyst (p=0.0265).


Prospective evaluation of ambulatory laser vaporization of the prostate for benign prostatic hyperplasia.
Photoselective vaporization of the prostate (PVP) is an alternative to transurethral resection of the prostate in the surgical treatment of benign prostatic hyperplasia (BPH). Our objective was to prospectively evaluate the feasibility, safety, and efficacy of ambulatory photoselective vaporization of the prostate for benign prostatic hyperplasia. We prospectively collected data of all consecutive patients who underwent ambulatory PVP with the Greenlight(®) laser 180-W XPS at two centers between May 2012 and June 2013. Patients' characteristics, perioperative data, postoperative outcomes, complications, and patient's satisfaction were evaluated. Successful ambulatory care procedure was defined as the ability to leave the hospital in the evening of the operation. The ambulatory procedure was intended in 134 patients. Mean age was 67 years. Mean prostate volume was 54 ml, and Median American Society Anesthesiologists (ASA) score was 2. Ambulatory procedure was successful in 121 patients (90%). At 3 months, International Prostate Symptom Score (7.3 ± 4.9), maximal urinary flow rate (20.8 ± 7.6 ml/s), postvoid residual urine (19.2 ± 71 ml), and quality of life (1.6 ± 1.4) were significantly improved (P < 0.001). Fourteen patients (10.5%) had complications that were all minor (Clavien ≤ 2). Two patients had to be readmitted to the hospital. The majority of patients (89%) were satisfied with ambulatory care. Failure to complete ambulatory procedure was mostly related to logistical problem (70% of the cases). Ambulatory PVP is feasible with functional results and complications comparable to that of traditional hospitalization. Ambulatory care yields high patient's satisfaction.


Elevated minimum inhibitory concentrations to antifungal drugs prevail in 14 rare species of candidemia-causing Saccharomycotina yeasts.
Antifungal susceptibility profiles of rare Saccharomycotina yeasts remain missing, even though an increase in prevalence of such rare Candida species was reported in candidemia. Majority of these rare yeast species carry intrinsic resistances against at least one antifungal compound. Some species are known to be cross-resistant (against multiple drugs of the same drug class) or even multi-drug resistant (against multiple drugs of different drug classes). We performed antifungal susceptibility testing (AFST) according to EUCAST broth microdilution for 14 rare species (Clavispora lusitaniae, Candida intermedia, Candida auris, Diutina rugosa, Wickerhamiella pararugosa, Yarrowia lipolytica, Pichia norvegensis, Candida nivariensis, Kluyveromyces marxianus, Wickerhamomyces anomalus, Candida palmioleophila, Meyerozyma guilliermondii, Meyerozyma caribbica, and Debaryomyces hansenii) known to cause candidemia. In total, 234 isolates were tested for amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, anidulafungin, micafungin, and caspofungin. Amphothericin B had the broadest efficiency against the 14 tested rare yeast species, while high minimum inhibitory concentrations (MICs) against azole drugs and echinocandins were common. Voriconazole was the most efficient azole drug. Multidrug resistance was observed for the species C. auris and K. marxianus. Multidrug resistant individual isolates were found for Y. lipolytica and M. caribbica. In conclusion, the observed high MIC values of the rare Saccharomycotina species tested limit antifungal treatment options, complicating the management of such infections.


Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009.
The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC.


K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation.
K(+) channels are central to vascular pathophysiology. Previous results demonstrated that phenotypic modulation associates with a change in Kv1.3 to Kv1.5 expression, and that Kv1.3 blockade inhibits proliferation of VSMCs cultures. To explore whether the Kv1.3 to Kv1.5 switch could be a marker of the increased risk of intimal hyperplasia in essential hypertension and whether systemic treatment with Kv1.3 blockers can prevent intimal hyperplasia after endoluminal lesion . Morphometric and immunohistochemical analysis were performed in arterial segments following arterial injury and constant infusion of the Kv1.3 blocker PAP-1 during 28 days. Differential expression of K(+) channel genes was studied in VSMC from hypertensive (BPH) and normotensive (BPN) mice, both in control and after endoluminal lesion. Finally, the migration and proliferation rate of BPN and BPH VSMCs was explored in vitro. Changes in mRNA expression led to an increased Kv1.3/Kv1.5 ratio in BPH VSMC. Consistent with this, arterial injury in BPH mice induced a higher degree of luminal stenosis, (84 ± 4% vs. 70 ± 5% in BPN, p < 0.01), although no differences in migration and proliferation rate were observed in cultured VSMCs. The in vivo proliferative lesions were significantly decreased upon PAP-1 systemic infusion (18 ± 6% vs. 58 ± 20% with vehicle, p < 0.05). Hypertension leads to a higher degree of luminal stenosis in our arterial injury model, that correlates with a decreased expression of Kv1.5 channels. Kv1.3 blockers decreased in vitro VSMCs proliferation, migration, and in vivo intimal hyperplasia formation, pointing to Kv1.3 channels as promising therapeutical targets against restenosis.


Devascularizing complications of free fibula harvest: peronea arteria magna.
The authors present a case report of devascularizing complications following free fibula harvest. A retrospective review of 93 consecutively imaged limbs demonstrated a peronea arteria magna (PAM) prevalence of 5.3 percent in an urban population, which was used to perform a cost-effectiveness analysis for preoperative vascular imaging of the donor limb using magnetic resonance angiography (MRA) and traditional angiography (TA). Donor-site complications of fibula harvest range from 15 to 30 percent, but are rarely limb-threatening. Limb loss is a dreaded complication of congenital PAM, which can be present with a normal vascular exam. Some microsurgery groups advocate using no preoperative imaging of the donor limb; they rely on intraoperative assessment of the vascular anatomy. An aborted harvest due to aberrant anatomy leads to both direct and indirect added costs. The authors believe that MRA imaging of the donor limb, being minimally invasive, is cost-effective and indicated for free fibula transfers. For equivocal results, conversion to more invasive and costly TA may be necessary.


COVID-19 Pandemic and Indigenous Representation in Public Health Data.
Public Health 3.0 calls for the inclusion of new partners and novel data to bring systemic change to the US public health landscape. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has illuminated significant data gaps influenced by ongoing colonial legacies of racism and erasure. American Indian and Alaska Native (AI/AN) populations and communities have been disproportionately affected by incomplete public health data and by the COVID-19 pandemic itself. Our findings indicate that only 26 US states were able to calculate COVID-19‒related death rates for AI/AN populations. Given that 37 states have Indian Health Service locations, we argue that public health researchers and practitioners should have a far larger data set of aggregated public health information on AI/AN populations. Despite enormous obstacles, local Tribal facilities have created effective community responses to COVID-19 testing, tracking, and vaccine administration. Their knowledge can lead the way to a healthier nation. Federal and state governments and health agencies must learn to responsibly support Tribal efforts, collect data from AI/AN persons in partnership with Indian Health Service and Tribal governments, and communicate effectively with Tribal authorities to ensure Indigenous data sovereignty. (Am J Public Health. 2021;111(S3): S208-S214. https://doi.org/10.2105/AJPH.2021.306415).


Using low-E resonators to reduce RF heating in biological samples for static solid-state NMR up to 900 MHz.
RF heating of solid-state biological samples is known to be a destabilizing factor in high-field NMR experiments that shortens the sample lifetime by continuous dehydration during the high-power cross-polarization and decoupling pulses. In this work, we describe specially designed, large volume, low-E 15N-1H solid-state NMR probes developed for 600 and 900 MHz PISEMA studies of dilute membrane proteins oriented in hydrated and dielectrically lossy lipid bilayers. The probes use an orthogonal coil design in which separate resonators pursue their own aims at the respective frequencies, resulting in a simplified and more efficient matching network. Sample heating at the 1H frequency is minimized by a loop-gap resonator which produces a homogeneous magnetic field B1 with low electric field E. Within the loop-gap resonator, a multi-turn solenoid closely matching the shape of the sample serves as an efficient observe coil. We compare power dissipation in a typical lossy bilayer sample in the new low-E probe and in a previously reported 15N-1H probe which uses a double-tuned 4-turn solenoid. RF loss in the sample is measured in each probe by observing changes in the 1H 360 degrees pulse lengths. For the same values of 1H B1 field, sample heating in the new probe was found to be smaller by an order of magnitude. Applications of the low-E design to the PISEMA study of membrane proteins in their native hydrated bilayer environment are demonstrated at 600 and 900 MHz.


Molecular model for a complete clathrin lattice from electron cryomicroscopy.
Clathrin-coated vesicles are important vehicles of membrane traffic in cells. We report the structure of a clathrin lattice at subnanometre resolution, obtained from electron cryomicroscopy of coats assembled in vitro. We trace most of the 1,675-residue clathrin heavy chain by fitting known crystal structures of two segments, and homology models of the rest, into the electron microscopy density map. We also define the position of the central helical segment of the light chain. A helical tripod, the carboxy-terminal parts of three heavy chains, projects inward from the vertex of each three-legged clathrin triskelion, linking that vertex to 'ankles' of triskelions centred two vertices away. Analysis of coats with distinct diameters shows an invariant pattern of contacts in the neighbourhood of each vertex, with more variable interactions along the extended parts of the triskelion 'legs'. These invariant local interactions appear to stabilize the lattice, allowing assembly and uncoating to be controlled by events at a few specific sites.


Evaluation of the genetic stability of the temperature-sensitive PB2 gene mutation of the influenza A/Ann Arbor/6/60 cold-adapted vaccine virus.
A single-gene reassortant bearing the PB2 gene of the A/Ann Arbor/6/60 cold-adapted virus in the background of the A/Korea/82 (H3N2) wild-type virus is a temperature-sensitive (ts) virus with an in vitro shutoff temperature of 38 degrees C. A single mutation at amino acid (aa) at 265 (Asp-Ser) of the PB2 protein is responsible for the ts phenotype. This ts single-gene PB2 reassortant virus was serially passaged at elevated temperatures in Madin-Darby canine kidney cells to generate ts+ phenotypic revertant viruses. Four ts+ phenotypically revertant viruses were derived independently, and each possessed a shutoff temperature for replication in vitro of > 40 degrees C. Each of the four phenotypically revertant viruses replicated efficiently in the upper and lower respiratory tracts of mice and hamsters, unlike the PB2 single-gene reassortant virus, confirming that the ts phenotype was responsible for the attenuation of this virus in rodents. Mating the ts+ revertants with wild-type virus yielded ts progeny in high frequency, indicating that the loss of ts phenotype was due to a suppressor mutation which was mapped to the PA gene in each of the four independently derived ts phenotypic revertants. Nucleotide sequence analysis confirmed the absence of new mutations on the PB2 gene and the presence of predicted amino acid changes in the PA proteins of the revertant viruses. These studies suggest that single amino acid changes at aa 245 (Glu-Lys) or 347 (Asp-Asn) of the PA protein can completely suppress the ts and attenuation phenotypes specified by the Asp-Ser mutation at aa 265 of the PB2 protein of the A/Ann Arbor/6/60 cold-adapted virus.


Metabolic flux responses to pyruvate kinase knockout in Escherichia coli.
The intracellular carbon flux distribution in wild-type and pyruvate kinase-deficient Escherichia coli was estimated using biosynthetically directed fractional 13C labeling experiments with [U-13C6]glucose in glucose- or ammonia-limited chemostats, two-dimensional nuclear magnetic resonance (NMR) spectroscopy of cellular amino acids, and a comprehensive isotopomer model. The general response to disruption of both pyruvate kinase isoenzymes in E. coli was a local flux rerouting via the combined reactions of phosphoenolpyruvate (PEP) carboxylase and malic enzyme. Responses in the pentose phosphate pathway and the tricarboxylic acid cycle were strongly dependent on the environmental conditions. In addition, high futile cycling activity via the gluconeogenic PEP carboxykinase was identified at a low dilution rate in glucose-limited chemostat culture of pyruvate kinase-deficient E. coli, with a turnover that is comparable to the specific glucose uptake rate. Furthermore, flux analysis in mutant cultures indicates that glucose uptake in E. coli is not catalyzed exclusively by the phosphotransferase system in glucose-limited cultures at a low dilution rate. Reliability of the flux estimates thus obtained was verified by statistical error analysis and by comparison to intracellular carbon flux ratios that were independently calculated from the same NMR data by metabolic flux ratio analysis.


Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.
Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.


Cortical areas and the control of self-determined finger movements: an fMRI study.
We investigated cortical areas involved in the control of self-determined finger movements. In a tapping task, subjects tapped with different movement frequencies in two different movement conditions (predetermined vs self-determined). fMRI provided evidence for the involvement of the horizontal and ascending parts of the intraparietal sulcus (IPS), the left superior frontal gyrus and the posterior cingulate gyrus in the control of self-determined finger movements. Higher movement frequency increased the extent of activated area only in the horizontal part of IPS. The results suggest a major role of the IPS in controlling sequences of finger movements. This area probably serves as a region for integration of motor, sensory and sensorimotor feedback information used for movement control.


The revival of the Gini importance?
Random forests are fast, flexible and represent a robust approach to analyze high dimensional data. A key advantage over alternative machine learning algorithms are variable importance measures, which can be used to identify relevant features or perform variable selection. Measures based on the impurity reduction of splits, such as the Gini importance, are popular because they are simple and fast to compute. However, they are biased in favor of variables with many possible split points and high minor allele frequency. We set up a fast approach to debias impurity-based variable importance measures for classification, regression and survival forests. We show that it creates a variable importance measure which is unbiased with regard to the number of categories and minor allele frequency and almost as fast as the standard impurity importance. As a result, it is now possible to compute reliable importance estimates without the extra computing cost of permutations. Further, we combine the importance measure with a fast testing procedure, producing p-values for variable importance with almost no computational overhead to the creation of the random forest. Applications to gene expression and genome-wide association data show that the proposed method is powerful and computationally efficient. The procedure is included in the ranger package, available at https://cran.r-project.org/package=ranger and https://github.com/imbs-hl/ranger. Supplementary data are available at Bioinformatics online.


Staurosporine, a protein kinase inhibitor, activates K-Cl cotransport in LK sheep erythrocytes.
K-Cl cotransport can participate in volume regulation in a number of cell types. Swelling activation of K-Cl cotransport in sheep erythrocytes proceeds by a two-step process, A<-->B<-->C (Dunham et al., J. Gen. Physiol. 101: 733-765, 1993). The A state, with a low flux, predominates at physiological volume. A-->B is rate limiting and can be activated by reducing cell Mg concentration ([Mg]c); complete activation (B-->C) requires cell swelling. Inhibitors of protein kinases and phosphatases were employed in an attempt to identify enzymatic reactions in the activation process. Staurosporine, a kinase inhibitor, activated K-Cl cotransport by approximately sixfold. Swelling of staurosporine-treated cells caused further activation that proceeded without delay. The effects of staurosporine and reducing [Mg]c were not additive. These two results indicate that staurosporine, like reducing [Mg]c, promotes the rate-limiting A-->B conversion. Unlike swelling, staurosporine activated cotransport without delay. Therefore staurosporine activates by promoting the forward reaction in the A<-->B conversions, in contrast to swelling, which activates by inhibiting the reverse reaction. Calyculin A, a phosphatase inhibitor, inhibited K-Cl cotransport but did not inhibit after activation by reducing [Mg]c, confirming earlier proposals that A-->B is promoted by a phosphatase. Calyculin A, added before or after staurosporine, abolished activation by staurosporine, confirming that staurosporine promotes A-->B. It is proposed that the phosphatase promoting this reaction is regulated by an inhibitory kinase, the staurosporine target.


Effects of raloxifene and alendronate on bone turnover as assessed by procollagen type I N-terminal propeptide.
Raloxifene decreases PINP into the lower half of the premenopausal reference interval; alendronate decreases PINP more, with approximately 60% of alendronate-treated women having PINP concentrations below the lower limit of the premenopausal reference interval. The purpose of this study was to evaluate the distribution of serum procollagen type I N-terminal propeptide (PINP) concentrations in women with postmenopausal osteoporosis prior to treatment and after treatment with either raloxifene or alendronate for 12 or more months. Included were data from 1,323 postmenopausal women aged 45 to 87 years, collected at baseline or after treatment with either alendronate 10 mg/day or raloxifene 60 mg/day. These patients had participated in one of four clinical trials in which intact PINP was measured by radioimmunoassay (Orion Diagnostica). A premenopausal reference interval from 16.0 to 75.8 μg/L was determined from 68 premenopausal, non-pregnant women. Most postmenopausal osteoporotic patients prior to treatment had PINP values in the upper half of the premenopausal reference interval at baseline (70%). After ≥ 12 months of therapy, most patients who received raloxifene had PINP concentrations in the lower half of the premenopausal reference interval (58%), whereas among those who received alendronate, around 60% of patients had PINP concentrations below the lower limit of the premenopausal reference interval. PINP may be useful for assessing differences in bone turnover response to different types of anti-resorptive therapy.


The effect of dentin desensitizer with different layers on thermal changes on the pulp during fabrication of provisional restoration.
This study investigated the effects of different desensitizers and an adhesive material application on pulpal temperature rise during direct provisional restoration polymerization. Two dentin desensitizers (Systemp, Ivoclar; BisBlock, Bisco) and a dentin adhesive (Prime Bond, Dentsply) were applied to the dentin surfaces as single layer or double layer. One autopolymerizing methacrylate (Prevision, Heraeus Kulzer) and one light polymerizing composite (Revotek LC, GC) provisional restoration materials were used in this study. A total of 160 dentin disks were prepared from extracted molars. These dentin disks were placed on an apparatus developed to measure temperature rise. After the desensitizer or dentin adhesive application, provisional materials were polymerized according to the manufacturers' instructions. The temperature increase was measured under the dentin disk with a J-type thermocouple wire that was connected to a data logger. Differences between initial and highest temperature reading were taken, and 10 readings were averaged to determine the mean value in temperature rise. Statistical analysis was performed with three-way analysis of variance followed by Tukey HSD test (alpha = 0.05). Temperature rise varied according to the provisional restoration material used (composite resin, methacrylate) (p < 0.001), the agent thickness (single, double) (p < 0.001), and the agent (desensitizer, adhesive) (p < 0.001). The composite resin-based provisional material induced higher thermal changes than methacrylate based provisional material (p < 0.01). The thickness of desensitizing agents affected the thermal changes; however, the desensitizers did not affect on the intrapulpal temperature although the type of provisional material used may be effective.