The quest for atmospheric methane oxidizers in forest soils.
Aerobic methanotrophs in forest soils are the largest biological sink for atmospheric methane (CH4 ). Community structures in 53 soils from Europe, Russia, North and South America, Asia and New Zealand located in boreal, temperate and tropical forests were analysed and maximal abundances of 2.1 × 10(7) methanotrophs g(-1) DW were measured. In acidic soils, the most frequently detected pmoA genotypes were Upland Soil Cluster α (USCα) and Methylocystis spp. Phospholipid fatty acids that were labelled by consumption of (14/13) CH4 suggested the activity of type II methanotrophs. Cluster 1 (Methylocystaceae), USCγ and Methylocystis spp. were frequently detected genotypes in pH-neutral soils. Genotypes with ambiguous functional affiliation were co-detected (Clusters MR1, RA21, 2) and may represent aerobic methanotrophs, ammonia oxidizers or enzymes with an unknown function. The physiological traits of atmospheric CH4 oxidizers are largely unknown because organisms possessing the key forest soil pmoA genotypes (USCα, USCγ, Cluster 1) have not been cultivated. Some methanotrophic strains belonging to the family Methylocystaceae have been shown to oxidize CH4 at atmospheric mixing ratios. Methylocystis strain SC2 was found to have an alternative particulate CH4 monooxygenase responsible for CH4 oxidation at atmospheric mixing ratios. pH, forest type and temperature might be environmental factors that shape methanotrophic communities in forest soils. However, specific effects on individual species are largely unknown, and only a limited number of studies have addressed environmental controls of methanotrophic diversity, pointing to the need for future research in this area.


Does dietary counseling improve quality of life in cancer patients? A systematic review and meta-analysis.
Results have been mixed as to whether dietary counseling improves clinical outcomes in cancer patients. This systematic review and meta-analysis of randomized trials assessed the effect of dietary counseling on quality of life (QOL). It included only randomized trials that focused on dietary counseling and that relied upon a standardized QOL measurement. Five trials that met these and all other a priori eligibility criteria were identified; they are the focus of this meta-analysis. When these five studies were examined in aggregate, the standardized mean difference in QOL scores among patients who received dietary counseling was 0.56 (95% confidence interval,-0.01-1.14; P = 0.06). Dietary counseling does not appear to improve QOL significantly in patients with cancer. However,an observed trend toward benefit underscores the need for further study.


In vivo expression and immunoadjuvancy of a mutant of heat-labile enterotoxin of Escherichia coli in vaccine and vector strains of Vibrio cholerae.
Vibrio cholerae secretes cholera toxin (CT) and the closely related heat-labile enterotoxin (LT) of Escherichia coli, the latter when expressed in V. cholerae. Both toxins are also potent immunoadjuvants. Mutant LT molecules that retain immunoadjuvant properties while possessing markedly diminished enterotoxic activities when expressed by E. coli have been developed. One such mutant LT molecule has the substitution of a glycine residue for arginine-192 [LT(R192G)]. Live attenuated strains of V. cholerae that have been used both as V. cholerae vaccines and as vectors for inducing mucosal and systemic immune responses directed against expressed heterologous antigens have been developed. In order to ascertain whether LT(R192G) can act as an immunoadjuvant when expressed in vivo by V. cholerae, we introduced a plasmid (pCS95) expressing this molecule into three vaccine strains of V. cholerae, Peru2, ETR3, and JRB14; the latter two strains contain genes encoding different heterologous antigens in the chromosome of the vaccine vectors. We found that LT(R192G) was expressed from pCS95 in vitro by both E. coli and V. cholerae strains but that LT(R192G) was detectable in the supernatant fraction of V. cholerae cultures only. In order to assess potential immunoadjuvanticity, groups of germfree mice were inoculated with the three V. cholerae vaccine strains alone and compared to groups inoculated with the V. cholerae vaccine strains supplemented with purified CT as an oral immunoadjuvant or V. cholerae vaccine strains expressing LT(R192G) from pCS95. We found that mice continued to pass stool containing V. cholerae strains with pCS95 for at least 4 days after oral inoculation, the last day evaluated. We found that inoculation with V. cholerae vaccine strains containing pCS95 resulted in anti-LT(R192G) immune responses, confirming in vivo expression. We were unable to detect immune responses directed against the heterologous antigens expressed at low levels in any group of animals, including animals that received purified CT as an immunoadjuvant. We were, however, able to measure increased vibriocidal immune responses against vaccine strains in animals that received V. cholerae vaccine strains expressing LT(R192G) from pCS95 compared to the responses in animals that received V. cholerae vaccine strains alone. These results demonstrate that mutant LT molecules can be expressed in vivo by attenuated vaccine strains of V. cholerae and that such expression can result in an immunoadjuvant effect.


Concern as motivation for protection: an investigation of mothers' concern about daughters' breast cancer risk.
The present study surveyed mothers with daughters (N = 386) to investigate how mothers' concern about their daughters' breast cancer risk influenced intentions to engage in preventive behaviors. Using protection motivation theory as a framework, self-efficacy, response efficacy, and level of concern were posited to influence protective behavioral intention in distinct ways. Results from regression analyses indicate that self-efficacy, response efficacy, and mothers' concern are significant predictors of intentions to engage in preventive behaviors with daughters. In addition, a content analysis of mothers' open-ended reasons for their concern about their daughters' breast cancer risk yield a list of specific concerns and trends that vary by concern level and individual comment valence. The authors discuss implications for incorporating mothers' concerns into breast cancer prevention messages as a novel strategy for campaign designers.


The importance of plain radiography in the evaluation of radiculopathy after failed diskectomy.
Herniated disks in the lumbar spine are the leading cause of patient visits to spinal surgeons in the United States. Although magnetic resonance imaging (MRI) is the diagnostic test of choice in patients with a herniated disk, plain radiographs can provide important information and should remain a standard part of the diagnostic workup in any patient indicated for revision spine surgery. This article describes a case of a 36-year-old man with a >6-month history of worsening lumbar radiculopathy who was diagnosed with lumbar disk herniations based on MRI alone and underwent 2 unsuccessful attempts at microdiskectomy at another institution. Further workup by the senior author (A.C.H.), which included initial plain radiographs followed by computed tomography, demonstrated a large disk herniation with a markedly calcified annulus as the continuing source of neurologic compression. The patient underwent revision lumbar decompression with attention being paid to the removal of the calcified annulus and disk material that resulted in complete resolution of his symptoms. Although MRI is the diagnostic test of choice in the evaluation of spinal pathology, plain radiographs can provide important additional information that can be vital to the successful outcome of patients undergoing revision spinal surgery.


The MHC class I peptide repertoire is molded by the transcriptome.
Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I-associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that approximately 25% of MHC I-associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K-AKT-mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I-associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.


Evolution of tyrosinemia type 1 disease in patients treated with nitisinone in Spain.
Treatment with nitisinone (NTBC) has brought about a drastic improvement in the treatment and prognosis of hereditary tyrosinemia type I (HT1). We conducted a retrospective observational multicentric study in Spanish HT1 patients treated with NTBC to assess clinical and biochemical long-term evolution.We evaluated 52 patients, 7 adults and 45 children, treated with NTBC considering: age at diagnosis, diagnosis by clinical symptoms, or by newborn screening (NBS); phenotype (acute/subacute/chronic), mutational analysis; symptoms at diagnosis and clinical course; biochemical markers; doses of NTBC; treatment adherence; anthropometric evolution; and neurocognitive outcome.The average follow-up period was 6.1 ± 4.9 and 10.6 ± 5.4 years in patients with early and late diagnosis respectively. All patients received NTBC from diagnosis with an average dose of 0.82 mg/kg/d. All NBS-patients (n = 8) were asymptomatic at diagnosis except 1 case with acute liver failure, and all remain free of liver and renal disease in follow-up. Liver and renal affectation was markedly more frequent at diagnosis in patients with late diagnosis (P < .001 and .03, respectively), with ulterior positive hepatic and renal course in 86.4% and 93.2% of no-NBS patients, although 1 patient with good metabolic control developed hepatocarcinoma.Despite a satisfactory global nutritional evolution, 46.1% of patients showed overweight/obesity. Interestingly lower body mass index was observed in patients with good dietary adherence (20.40 ± 4.43 vs 24.30 ± 6.10; P = .08) and those with good pharmacological adherence (21.19 ± 4.68 vs 28.58 ± 213.79).intellectual quotient was ≥85 in all NBS- and 68.75% of late diagnosis cases evaluated, 15% of which need pedagogical support, and 6.8% (3/44) showed school failure.Among the 12 variants identified in fumarylacetoacetate hydrolase gene, 1 of them novel (H63D), the most prevalent in Spanish population is c.554-1 G>T.After NTBC treatment a reduction in tyrosine and alpha-fetoprotein levels was observed in all the study groups, significant for alpha-fetoprotein in no NBS-group (P = .03), especially in subacute/chronic forms (P = .018).This series confirms that NTBC treatment had clearly improved the prognosis and quality of life of HT1 patients, but it also shows frequent cognitive dysfunctions and learning difficulties in medium-term follow-up, and, in a novel way, a high percentage of overweight/obesity.


Isolation and characterization of a prenylcysteine lyase from bovine brain.
Prenylated proteins contain one of two isoprenoid lipids, either the 15-carbon farnesyl or the 20-carbon geranylgeranyl, covalently attached to cysteine residues at or near their C terminus. The cellular abundance of prenylated proteins, which can comprise up to 2% of total cellular protein, raises the question of how cells dispose of prenylcysteines produced during the normal turnover of prenylated proteins. We have identified and characterized a novel enzyme, which we term prenylcysteine lyase, that is capable of cleaving the thioether bond of prenylcysteines. The enzyme was isolated from bovine brain membranes and exhibits an apparent molecular mass of 63 kDa. The enzyme did not require NADPH as cofactor for prenylcysteine degradation, thus distinguishing it from cytochrome P450- and flavin-containing monooxygenases that catalyze S-oxidation of thioethers. Purified prenylcysteine lyase shows similar kinetics in utilization of both farnesylcysteine and geranylgeranylcysteine as substrates, although Vmax is 2-fold higher with the former compound. Interaction of prenylcysteine substrates with the enzyme requires that they possess a free amino group; N-acetylated prenylcysteines and prenyl peptides are not substrates. These findings suggest that prenylcysteine lyase is a specific enzyme involved in prenylcysteine metabolism in mammalian cells, most likely comprising the final step in the degradation of prenylated proteins.


Influence of overlying tissue and probe geometry on the sensitivity of a near-infrared tissue oximeter.
In this paper, the influences of overlying tissue and detecting distance between the source and the detector on the measurement of a tissue oximeter were discussed. The signal-noise-ratio of the detector was also examined. A semi-infinite multi-layer Monte Carlo model was induced to simulate the migration of the photons in the skin, adipose and muscle. The thickness of the adipose layer and the separation between the source and the detector in the muscle were changed to simulate the clinical application. Partial pathlength was introduced as a characteristic parameter to evaluate the sensitivity of the oximeter. A two-wavelength (700 and 830 nm) tissue oximeter was developed to verify the results of the simulation. The Monte Carlo simulation results showed that the sensitivity of the near infrared spectroscopy (NIRS) oximeter declined greatly with increasing overlying tissue thickness. Increasing the distance between the light source and the detector improved the sensitivity. However, in order to achieve a sufficiently high signal-to-noise ratio, it was necessary to limit this distance. The results of a bicycle ergometer exercise verified the above results and showed that, for a special adipose thickness (AT), there may be a reasonable range of the emitter-detector separation.


Changes of oscillatory brain activity induced by repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in healthy subjects.
Repetitive transcranial magnetic stimulation (rTMS) modulates brain activity in different ways according to the stimulation parameters. Although the after-effects of rTMS over motor cortex are well documented in healthy individuals, less is known about the stimulation of dorso-lateral prefrontal cortex (DLPFC). Here, we studied in 20 healthy subjects how cortical oscillations are modulated by four different active rTMS protocols (1Hz, 10Hz, continuous and intermittent theta bursts - cTBS and iTBS) of the left DLPFC, and by a sham protocol used as a control condition, by comparing the spectral power of pre- and post-rTMS electroencephalographic (EEG) recordings of 15min duration. EEG spectrum was estimated with the fast Fourier transform (FFT) and partitioned using the common physiological frequency bands: delta (1-4Hz), theta (3.5-7Hz), alpha (7.5-13Hz), low beta (14-22Hz), high beta (22-30Hz) and gamma (30-45Hz). Statistical analyses of EEG changes induced by rTMS were computed with Statistical Parametric Mapping (SPM) for EEG, in every frequency band, at the scalp level and at the cortex level. We found for every active protocol a significant decrease of delta and theta power on left prefrontal electrodes, mainly localised in the left DLPFC. In higher frequency bands (beta and gamma), the decrease of power in the DLPFC was also observed contralaterally. Protocol-specific amplitude effects were found in the prefrontal cortex bilaterally in all frequency bands, but also in parietal and temporal regions in low EEG frequencies. In high frequencies, EEG power in the prefrontal cortex increased after rTMS for 10Hz and iTBS protocols, but this effect did not survive the comparison to Sham responses. Because large delta and theta activity is usually associated with cortical inhibition, observed rTMS-induced EEG changes in low frequencies suggest that rTMS of DLPFC transiently decreases local cortical inhibition. Importantly, local responses take place in association with other unknown mechanisms that modulate inter-hemispheric connectivity between homologous regions, resulting in the increase or decrease of fast activity in each prefrontal lobe, depending on the stimulation protocol. Only decreases of fast activity following active rTMS could be detected as significant when compared to Sham stimulation.


Antimicrobial therapy of experimental intraabdominal sepsis.
Septic complications of colonic perforation involve miltiple bacteria derived from the intestinal flora. This type of mixed intraabdominal infection was produced experimentally by insertion of a standardized inoculum of rat colonic contents into the peritoneal cavity of male Wistar rats. The respective roles of coliforms and anerobic bacteria were then studied by use of selective antimicrobial therapy (with gentamicin and clindamycin). Untreated rats had a two-stage disease. Initally, there was an acute peritonitis associated with a 37% mortality rate; all animals that survived developed indolent intraabdominal abscesses. Treatment with gentamicin reduced the acute mortality rate to 4%, but 98% of the survivors had abscesses. Clindamycin acute mortalherapy was associated with a 35% mortality rate, but the incidence of intraabdominal abscess was only 5%. A combination of gentamicin and clindamycin yielded the salutary effects of each agent--7% mortality and 6% incidence of abscesses. These studies, in concert with bacteriological findings, suggest that coliforms caused early mortality while anaerobes were primarily responsible for the late complication of intraabdominal abscess formation.


A complex cell-like receptive field obtained by information maximization.
The energy model (Pollen & Ronner, 1983; Adelson & Bergen, 1985) for a complex cell in the visual cortex is investigated theoretically. The energy model describes the output of a complex cell as the squared sum of outputs of two linear operators. An information-maximization problem to determine the two linear operators is investigated assuming the low signal-to-noise ratio limit and a localization term in the objective function. As a result, two linear operators characterized by a quadrature pair of Gabor functions are obtained as solutions. The result agrees with the energy model, which well describes the shift-invariant and orientation-selective responses of actual complex cells, and thus suggests that complex cells are optimally designed from an information-theoretic viewpoint.


Invasion category-oriented lymph node metastases of cholangiocarcinoma and the prognostic impact.
It was speculated that intrahepatic cholangiocarcinoma (ICC) invasion would influence cancer progression, such as lymph node (LN) metastasis, and the efficacy of LN dissection (LND). The purpose of this study is to evaluate the LN metastatic pattern of intrahepatic cholangiocarcinoma, including the invasion category and prognosis after surgical resection, in order to explore effective LND. We analyzed a prospectively collected cohort for ICC with a previously reported invasion category: hilar type, showing invasion to the main or first branch of Glisson; peripheral type, showing no invasion to less than the third branch; and intermediate type, for all others. Data from a total of 180 patients who underwent surgical resection were analyzed (LN dissection in 142 (79%)). In single ICC, hilar type had a higher LN metastatic rate than the others (hilar; 23/45 (51%), intermediate; 7/25 (28%), peripheral; 1/34 (3%)). Although the survival with LN metastasis (LN+) was worse, single and hilar/intermediate ICC LN+ had a better survival than peripheral type LN+ (3-year OS: hilar/intermediate 30-37%, peripheral 0%). The most frequent LN metastatic region was the hepatico-duodenal ligament for all invasion categories, and the LN metastatic region was not related to the survival. In peripheral ICC, LND did not affect the survival. By contrast, hilar/intermediate ICC LN+ had a better survival than did peripheral ICC LN+, and the 3-year OS was ≥ 20%. LN metastasis depended on the ICC invasion category in addition to the tumor number, which affected patients' survival and the need for LND. In hilar-type disease, LN dissection may contribute to the survival.


Antibodies to intermediate filaments in polymyalgia rheumatica and giant cell arteritis: a sequential study.
Serum specimens from 35 patients with polymyalgia rheumatica and giant cell arteritis (PMR/GCA) were obtained sequentially at variable time intervals up to a year from onset of disease. These were tested for antibodies to intermediate filaments by indirect immunofluorescence using HEp2 cells as substrate. Twenty four of 35 (68%) patients' sera at onset of disease were positive at an anti-intermediate filament antibody (AIFA) titre of greater than 1/40 compared with three outs of 19 (15%) control sera. AIFA were predominantly of IgM class, and there was no significant change in AIFA titres on follow up despite clinical remission of disease.


School Racial Composition as a Moderator of the Effect of Discrimination on Mental Health and Substance use Among American Indian Adolescents.
To examine the relationships between individual-level perceived racial/ethnic discrimination and mental health and substance use outcomes by school-level racial composition among American Indian (AI) adolescents. Self-reported survey data on individual-level variables come from a sample of AI adolescents (n = 510) living in or near the Cherokee Nation during the fall of 2021. School-level data come from publicly available databases. Multilevel linear and logistic regression analyses were performed to test for and examine the interaction between perceived racial/ethnic discrimination and school racial composition in relation to symptoms of anxiety and depression, past 30-day use of alcohol and marijuana, and misuse of prescription opioids. Adjusted analyses showed a significant interaction effect between discrimination and racial composition on anxiety symptoms, such that the effect of discrimination was more pronounced at lower % AI (10th percentile) than at more equivalently mixed (50th percentile) or higher % AI (90th percentile) school settings. No significant interactions were observed with depressive symptoms or substance use outcomes. School racial compositions of higher percentage AI may buffer the adverse effect of racial/ethnic discrimination on anxiety symptoms among AI adolescents.


Memory Attention Networks for Skeleton-Based Action Recognition.
Skeleton-based action recognition has been extensively studied, but it remains an unsolved problem because of the complex variations of skeleton joints in 3-D spatiotemporal space. To handle this issue, we propose a newly temporal-then-spatial recalibration method named memory attention networks (MANs) and deploy MANs using the temporal attention recalibration module (TARM) and spatiotemporal convolution module (STCM). In the TARM, a novel temporal attention mechanism is built based on residual learning to recalibrate frames of skeleton data temporally. In the STCM, the recalibrated sequence is transformed or encoded as the input of CNNs to further model the spatiotemporal information of skeleton sequence. Based on MANs, a new collaborative memory fusion module (CMFM) is proposed to further improve the efficiency, leading to the collaborative MANs (C-MANs), trained with two streams of base MANs. TARM, STCM, and CMFM form a single network seamlessly and enable the whole network to be trained in an end-to-end fashion. Comparing with the state-of-the-art methods, MANs and C-MANs improve the performance significantly and achieve the best results on six data sets for action recognition. The source code has been made publicly available at https://github.com/memory-attention-networks.


[Hilar glissonean access to vascular-secretory elements in anatomical segmental liver resections].
It still remains unclear which patients with hepatic tumors can favour anatomical segmental liver resections instead of major liver resection. Short term results of anatomical segmental liver resection are evaluated and analyzed. Ten patients underwent the anatomical segmental liver resection performed by posterior approach with taping of anterior right hepatic vein. Seven patients had liver metastases of colorectal cancer, one had primary hepatic carcinoma and two had benign lesions, anatomical segmental liver resection were performed without Pringle maneuver. There was no significant difference in blood loss, duration of the procedure, postoperative hospital stay and morbidity in comparison with the segmental liver resection performed by anterior approach. Multiple, large and deep-embedded lesions were removed completely, with tumor-free resection margins. Anatomical segmental liver resection performed by hilar glissonean approach is recommended in patients with compromised liver function "unfavourable" liver anatomy to replace major liver resection provides removal of only affected part of the liver accordingly to its true anatomical borders.


The spread of herpes simplex virus type 1 from trigeminal neurons to the murine cornea: an immunoelectron microscopy study.
An animal model has been developed to clarify the mechanism for spread of herpes simplex virus (HSV) from neuron to epithelial cells in herpetic epithelial keratitis. HSV was introduced into the murine trigeminal ganglion via stereotaxic guided injection. After 2 to 5 days, the animals were euthanized. Ganglia and corneas were prepared for light and electron microscopic immunocytochemistry with antisera to HSV. At 2 days, labeled axons were identified in the stromal layer. At 3 days, we could detect immunoreactive profiles of trigeminal ganglion cell axons that contained many vesicular structures. By 3 and 4 days, the infection had spread to all layers of epithelium, and the center of a region of infected epithelium appeared thinned. At 5 day, fewer basal cells appeared infected, although infection persisted in superficial cells where it had expanded laterally. Mature HSV was found in the extracellular space surrounding wing and squamous cells. Viral antigen was expressed in small pits along the apical surfaces of wing and squamous cells but not at the basal surface of these cells or on basal cells. This polarized expression of viral antigen resulted in the spread of HSV to superficial cells and limited lateral spread to neighboring basal cells. The pathogenesis of HSV infection in these mice may serve as a model of the human recurrent epithelial disease in the progression of focal sites of infection and transfer from basal to superficial cells.


Periprosthetic bone remodeling. A finite elementstudy of the influence of the implant design.
Remodeling periprosthetic femoral bone after total hip arthroplasty has been studied extensively. Finite element (FE) analysis, together with mathematical remodeling theories, has predicted that femoral bone-mineral density decreases proximally after total hip arthroplasty. There is significant controversy concerning the clinical consequences of bone remodeling such as the reduction in bone strength, the possibility of a cement mantle fracture, the aseptic loosening of the implant, or the appearance of a periprosthetic fracture, which could threaten the survival of the hip prosthesis. The status of periprosthetic bone stock is an important concern when total hip arthroplasty revision is undertaken. This study was conducted to evaluate the periprosthetic bone-mineral density evolution following primary total hip arthroplasty by FE analysis. We compared two cemented stems with different designs: the Exeter and the SHP to study the phenomenon of femoral stress shielding and bone cement deterioration. We found that with the best mechanical conditions and with the same materials, the prosthesis design determines a different periprosthetic bone remodeling.


Morphology of the core fibrous layer of the cetacean tail fluke.
The cetacean tail fluke blades are not supported by any vertebral elements. Instead, the majority of the blades are composed of a densely packed collagenous fiber matrix known as the core layer. Fluke blades from six species of odontocete cetaceans were examined to compare the morphology and orientation of fibers at different locations along the spanwise and chordwise fluke blade axes. The general fiber morphology was consistent with a three-dimensional structure comprised of two-dimensional sheets of fibers aligned tightly in a laminated configuration along the spanwise axis. The laminated configuration of the fluke blades helps to maintain spanwise rigidity while allowing partial flexibility during swimming. When viewing the chordwise sectional face at the leading edge and mid-chord regions, fibers displayed a crossing pattern. This configuration relates to bending and structural support of the fluke blade. The trailing edge core was found to have parallel fibers arranged more dorso-ventrally. The fiber morphology of the fluke blades was dorso-ventrally symmetrical and similar in all species except the pygmy sperm whale (Kogia breviceps), which was found to have additional core layer fiber bundles running along the span of the fluke blade. These additional fibers may increase stiffness of the structure by resisting tension along their long spanwise axis.


Law Enforcement Agencies' Perceptions of the Benefits of and Barriers to Temporary Firearm Storage to Prevent Suicide.
To examine the perceived benefits of and barriers to law enforcement agencies providing increased access to voluntary and temporary firearm storage. We surveyed 448 police chiefs and sheriffs in 8 US Mountain West states about firearm storage practices, benefits of and barriers to storage, and related attitudes and beliefs. Data collection occurred during the spring and summer of 2016. Nearly three quarters of agencies reported that they are already providing storage and perceive relatively few barriers in doing so. Agency characteristics were not associated with current provision of firearm storage. Among the barriers identified included state laws, limited space, training needs, and community perceptions. Benefits of storage included being perceived positively by the community and supporting health care workers. Engaging with law enforcement agencies in suicide prevention efforts and addressing their perceived barriers to providing temporary firearm storage have promise as part of a comprehensive suicide prevention approach.


Molecular cytogenetics in haematological malignancy: current technology and future prospects.
Cytogenetics has played a pivotal role in haematological malignancy, both as an aid to diagnosis and in identifying recurrent chromosomal rearrangements, an essential prerequisite to identifying genes involved in leukaemia and lymphoma pathogenesis. In the late 1980s, a series of technologies based around fluorescence in situ hybridisation (FISH) revolutionised the field. Interphase FISH, multiplex-FISH (M-FISH, SKY) and comparative genomic hybridisation (CGH) have emerged as the most significant of these. More recently, microarray technologies have come to prominence. In the acute leukaemias, the finding of characteristic gene expression signatures corresponding to biological subgroups has heralded gene expression profiling as a possible future alternative to current cytogenetic and morphological methods for diagnosis. In the lymphomas, high-resolution array CGH has successfully identified new regions of deletion and amplification, providing the prospect of disease-specific arrays.


Predicting mortality in damage control surgery for major abdominal trauma.
Damage control surgery (DCS) has become well established in the past decade as the surgical strategy to be employed in the unstable trauma patient. The aim of this study was to determine which factors played a predictive role in determining mortality in patients undergoing a damage control laparotomy. A retrospective review of all patients undergoing a laparotomy and DCS in a level 1 trauma centre over a 3-year period was performed. Twenty-nine potentially predictive variables for mortality were analysed. Of a total of 1 274 patients undergoing a laparotomy for trauma, 74 (6%) required a damage control procedure. The mean age was 28 years (range 14 - 53 years). The mechanism of injury was gunshot wounds in 57 cases (77%), blunt trauma in 14 (19%) and stabs in 3 (4%). Twenty patients died, giving an overall mortality rate of 27%. Factors significantly associated with increased mortality were increasing age (p=0.001), low base excess (p=0.002), pH (p<0.001), core temperature (p=0.002), and high blood transfusion requirement over 24 hours (p=0.002). The overall survival of patients after damage control procedures for abdominal trauma was excellent (73%). The main factors that are useful in deciding when to initiate DCS are age, base excess, pH and the core temperature.


The combined effect of subjective body image and body mass index (distorted body weight perception) on suicidal ideation.
Mental health disorders and suicide are an important and growing public health concern in Korea. Evidence has shown that both globally and in Korea, obesity is associated with an increased risk of developing some psychiatric disorders. Therefore, we examined the association between distorted body weight perception (BWP) and suicidal ideation. Data were obtained from the 2007-2012 Korea National Health and Nutritional Evaluation Survey (KNHANES), an annual cross-sectional nationwide survey that included 14 276 men and 19 428 women. Multiple logistic regression analyses were conducted to investigate the associations between nine BWP categories, which combined body image (BI) and body mass index (BMI) categories, and suicidal ideation. Moreover, the fitness of our models was verified using the Akaike information criterion. Consistent with previous studies, suicidal ideation was associated with marital status, household income, education level, and perceived health status in both genders. Only women were significantly more likely to have distorted BWP; there was no relationship among men. In category B1 (low BMI and normal BI), women (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.48 to 3.42) were more likely to express suicidal ideation than women in category B2 (normal BMI and normal BI) were. Women in overweight BWP category C2 (normal BMI and fat BI) also had an increased OR for suicidal ideation (OR, 2.25; 95% CI, 1.48 to 3.42). Those in normal BWP categories were not likely to have suicidal ideation. Among women in the underweight BWP categories, only the OR for those in category A2 (normal BMI and thin BI) was significant (OR, 1.34; 95% CI, 1.13 to 1.59). Distorted BWP should be considered an important factor in the prevention of suicide and for the improvement of mental health among Korean adults, especially Korean women with distorted BWPs.


Ecosystems of national parks.
The preservation and maintenance of natural park ecosystems, with modern man's being restricted to generally nonconsumptive uses of the park, represents one end of a spectrum of land use that extends through exploitation of natural ecosystems to the development of simplified agricultural ecosystems. Criteria for management of a park ecosystem must, of necessity, differ from criteria for other uses of land, since park management involves preventing or compensating for the influence of man. The objectives for natural areas appear to be ecologically feasible if it is recognized that these areas have a finite capacity for absorbing man's consumptive and disruptive influences. The interpretation of ecosystems to park visitors provides an opportunity to contribute to an environmental ethic that extends beyond the park environment.


Shc coordinates signals from intercellular junctions and integrins to regulate flow-induced inflammation.
Atherosclerotic plaques develop in regions of the vasculature associated with chronic inflammation due to disturbed flow patterns. Endothelial phenotype modulation by flow requires the integration of numerous mechanotransduction pathways, but how this is achieved is not well understood. We show here that, in response to flow, the adaptor protein Shc is activated and associates with cell-cell and cell-matrix adhesions. Shc activation requires the tyrosine kinases vascular endothelial growth factor receptor 2 and Src. Shc activation and its vascular endothelial cadherin (VE-cadherin) association are matrix independent. In contrast, Shc binding to integrins requires VE-cadherin but occurs only on specific matrices. Silencing Shc results in reduction in both matrix-independent and matrix-dependent signals. Furthermore, Shc regulates flow-induced inflammatory signaling by activating nuclear factor kappaB-dependent signals that lead to atherogenesis. In vivo, Shc is activated in atherosclerosis-prone regions of arteries, and its activation correlates with areas of atherosclerosis. Our results support a model in which Shc orchestrates signals from cell-cell and cell-matrix adhesions to elicit flow-induced inflammatory signaling.


The role of the tectal column in facilitation of amphibian prey-catching behavior: a neural model.
We used computer analysis of differential equations to study the properties of a family of models of a unit of neural circuitry in the amphibian tectum, the tectal column. Computer experiments were used to discriminate among various hypotheses and to suggest new experiments. Particular attention was paid to physiological data on facilitation of amphibian prey-catching behavior which led us to model the facilitation in terms of dynamic activity in the tectal column rather than in terms of synaptic modification.


Periodontal disease and metabolic syndrome: a qualitative critical review of their association.
Metabolic syndrome (MetS) is a conglomerate of several physical conditions/diseases that, as a group, increases the risk of mortality resulting from development of T2DM and cardiovascular diseases (CVD). These conditions/diseases include glucose intolerance/insulin resistance, hypertension, obesity, and dyslipidemia. The results from epidemiological studies suggest that there is an association between metabolic syndrome (MetS) and periodontitis, it is therefore important to understand the current status of the association and a possible contribution of periodontitis to MetS. This review will qualitatively analyze published papers on the association of MetS and periodontitis/periodontal disease to clarify the current status of the association and suggest future directions for studies which may unravel the causal relationship between them. Of 309 papers related to MetS and periodontitis, 26 are original research papers that investigated the relationship/association between periodontal disease and MetS. Criteria used to assess periodontitis and MetS as well as overall study designs and patient recruitment criteria varied greatly among these studies. All these studies demonstrated a positive association between periodontal disease and MetS. However, due to the heterogeneity of criteria to assess periodontitis and MetS and also paucity of longitudinal studies, it is difficult to determine the relative contribution of periodontitis to MetS. Age and the number of positive components of MetS appear to strengthen the relationship, however, incidence of each disease entity increases with ageing. Thus, mechanistic studies are also necessary to unravel the inter-relationship between periodontitis and MetS. In this regard, a use of animal models will be helpful as they are more uniform in regards to genetic background and have minimum confounding factors. Finally, development of accurate, quantitative assessment of gingival inflammation are necessary in order to determine the influence of periodontal disease on the development of MetS and its components.


Human Genetic Research in Wallacea and Sahul: Recent Findings and Future Prospects.
Genomic sequence data from worldwide human populations have provided a range of novel insights into our shared ancestry and the historical migrations that have shaped our global genetic diversity. However, a comprehensive understanding of these fundamental questions has been impeded by the lack of inclusion of many Indigenous populations in genomic surveys, including those from the Wallacean archipelago (which comprises islands of present-day Indonesia located east and west of Wallace's and Lydekker's Lines, respectively) and the former continent of Sahul (which once combined New Guinea and Australia during lower sea levels in the Pleistocene). Notably, these regions have been important areas of human evolution throughout the Late Pleistocene, as documented by diverse fossil and archaeological records which attest to the regional presence of multiple hominin species prior to the arrival of anatomically modern human (AMH) migrants. In this review, we collate and discuss key findings from the past decade of population genetic and phylogeographic literature focussed on the hominin history in Wallacea and Sahul. Specifically, we examine the evidence for the timing and direction of the ancient AMH migratory movements and subsequent hominin mixing events, emphasising several novel but consistent results that have important implications for addressing these questions. Finally, we suggest potentially lucrative directions for future genetic research in this key region of human evolution.


A unified 3D map of microscopic architecture and MRI of the human brain.
We present the first three-dimensional (3D) concordance maps of cyto- and fiber architecture of the human brain, combining histology, immunohistochemistry, and 7-T quantitative magnetic resonance imaging (MRI), in two individual specimens. These 3D maps each integrate data from approximately 800 microscopy sections per brain, showing neuronal and glial cell bodies, nerve fibers, and interneuronal populations, as well as ultrahigh-field quantitative MRI, all coaligned at the 200-μm scale to the stacked blockface images obtained during sectioning. These unprecedented 3D multimodal datasets are shared without any restrictions and provide a unique resource for the joint study of cell and fiber architecture of the brain, detailed anatomical atlasing, or modeling of the microscopic underpinnings of MRI contrasts.


Inhalational anesthetics disrupt postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 domain protein interactions critical to action of several excitatory receptor channels related to anesthesia.
The authors have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. The study data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. Glutathione S-transferase pull-down assay, coimmunoprecipitation, and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1-3 domains of PSD-95. A surface plasmon resonance-based BIAcore (Sweden) assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time. Halothane and isoflurane dose-dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluA2 and its interacting proteins-glutamate receptor-interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide-binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide-binding groove of PSD-95 PDZ3. These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia, and pain processing.


Reliability of a Field Test of Defending and Attacking Agility in Australian Football and Relationships to Reactive Strength.
Young, WB and Murray, MP. Reliability of a field test of defending and attacking agility in Australian football and relationships to reactive strength. J Strength Cond Res 31(2): 509-516, 2017-Defending and attacking agility tests for Australian football do not exist, and it is unknown whether any physical qualities correlate with these types of agility. The purposes of this study were to develop new field tests of defending and attacking agility for Australian Rules football, to determine whether they were reliable, and to describe the relationship between the agility tests to determine their specificity. Because the reactive strength (RS) of the lower limb muscles has been previously correlated with change-of-direction speed, we also investigated the relationship between this quality and the agility tests. Nineteen male competitive recreational-level Australian Rules football players were assessed on the agility tests and a drop jump test to assess RS. Interday and interrater reliability was also assessed. The agility tests involved performing 10 trials of one-on-one agility tasks against 2 testers (opponents), in which the objective was to be in a position to tackle (defending) or to evade (attacking) the opponent. Both agility tests had good reliability (intraclass correlation > 0.8, %CV < 3, and no significant differences between test occasions [p > 0.05], and interrater reliability was very high [r = 0.997, p < 0.001]). The common variance between the agility tests was 45%, indicating that they represented relatively independent skills. There was a large correlation between RS and defending agility (r = 0.625, p = 0.004), and a very large correlation with attacking agility (r = 0.731, p < 0.001). Defending and attacking agility have different characteristics, possibly related to the footwork, physical, and cognitive demands of each. Nonetheless, RS seems to be important for agility, especially for attacking agility.


Pneumothorax complicating fracture of the scapula.
We evaluated thirty patients with a fracture of the scapula in a prospective study over a seven-year period. Sixteen patients were found to have an associated pneumothorax, of which more than two-thirds were associated with a fracture of the left scapula. Ten of the pneumothoraces were delayed for one to three days. All of the scapular fractures were treated using a shoulder immobilizer, and early range-of-motion exercises of the involved extremity were instituted as tolerated. Information obtained from pulmonary auscultation and percussion, determination of initial values for arterial blood gases, and daily chest radiographs for three days after injury confirmed the diagnosis. Closed suction drainage using anteriorly or laterally placed thoracostomy tubes was performed successfully in all patients and avoided the potential sequelae of shock, respiratory failure, and pneumonia, as well as recurrence.


Diagnostic performance of 18F-FET PET in newly diagnosed cerebral lesions suggestive of glioma.
The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET in the initial diagnosis of cerebral lesions suggestive of glioma. In a retrospective study, we analyzed the clinical, radiologic, and neuropathologic data of 174 patients (77 women and 97 men; mean age, 45 ± 15 y) who had been referred for neurosurgical assessment of unclear brain lesions and had undergone (18)F-FET PET. Initial histology (n = 168, confirmed after surgery or biopsy) and the clinical course and follow-up MR imaging in 2 patients revealed 66 high-grade gliomas (HGG), 77 low-grade gliomas (LGG), 2 lymphomas, and 25 nonneoplastic lesions (NNL). In a further 4 patients, initial histology was unspecific, but during the course of the disease all patients developed an HGG. The diagnostic value of maximum and mean tumor-to-brain ratios (TBR(max/)TBR(mean)) of (18)F-FET uptake was assessed using receiver-operating-characteristic (ROC) curve analyses to differentiate between neoplastic lesions and NNL, between HGG and LGG, and between high-grade tumor (HGG or lymphoma) and LGG or NNL. Neoplastic lesions showed significantly higher (18)F-FET uptake than NNL (TBR(max), 3.0 ± 1.3 vs. 1.8 ± 0.5; P < 0.001). ROC analysis yielded an optimal cutoff of 2.5 for TBR(max) to differentiate between neoplastic lesions and NNLs (sensitivity, 57%; specificity, 92%; accuracy, 62%; area under the curve [AUC], 0.76; 95% confidence interval [CI], 0.68-0.84). The positive predictive value (PPV) was 98%, and the negative predictive value (NPV) was 27%. ROC analysis for differentiation between HGG and LGG (TBR(max), 3.6 ± 1.4 vs. 2.4 ± 1.0; P < 0.001) yielded an optimal cutoff of 2.5 for TBR(max) (sensitivity, 80%; specificity, 65%; accuracy, 72%; AUC, 0.77; PPV, 66%; NPV, 79%; 95% CI, 0.68-0.84). Best differentiation between high-grade tumors (HGG or lymphoma) and both NNL and LGG was achieved with a TBR(max) cutoff of 2.5 (sensitivity, 79%; specificity, 72%; accuracy, 75%; AUC, 0.79; PPV, 65%; NPV, 84%; 95% CI, 0.71-0.86). The results for TBR(mean) were similar with a cutoff of 1.9. (18)F-FET uptake ratios provide valuable additional information for the differentiation of cerebral lesions and the grading of gliomas. TBR(max) of (18)F-FET uptake beyond the threshold of 2.5 has a high PPV for detection of a neoplastic lesion and supports the necessity of an invasive procedure, for example, biopsy or surgical resection. Low (18)F-FET uptake (TBR(max) < 2.5) excludes a high-grade tumor with high probability.


An erythrocyte-sensitising antigen from Vibrio cholerae.
Erythrocyte-sensitising antigens (AE) were prepared from Vibrio cholerae serotypes, from EL-Tor vibrio, Escherichia coli and Salmonella enteritidis by digesting the organisms with NaOH followed by precipitation with alcohol. When AE was used in indirect haemagglutination (IHA) tests, the results in a number of cases were somewhat more sensitive and more specific than those obtained in classical agglutination tests. No cross reactions occurred between V. cholerae serotypes and E. coli and S. enteritidis. Much of the reactive part of the AE was not sedimentable at 100,000 g for 1 h. The eluant from the B. cholerae AE on Sephadex G-200 yielded three fractions, one of which was the most active in IHA tests. Treatment of the AE with trypsin resulted in an appreciable increase in the heterotypic serum titres in IHA tests. The spectrophotometric absorption of the AE at 260 nm showed a hump that may have been indicative of the presence of nucleic acid. Treatment of the antigen with ribonuclease reduced its nucleic acid content but did not change to any significant extent the reactivity of the preparation. The AE antigen of V. cholerae was Molisch-positive and was capable of sensitising untanned erythrocytes in IHA tests. It is suggested that the reactive part of the AE antigen is a carbohydrate complex.


Reserve-driven flow control for extracorporeal life support: proof of principle.
Extracorporeal life support systems lack volume-buffering capacity. Therefore, any decrease in venous intravascular volume available for drainage may result in acutely reduced support flow. We recently developed a method to quantify drainable volume and now conceived a reserve-driven pump control strategy, which is different from existing pressure or flow servo control schemes. Here, we give an outline of the algorithm and present animal experimental data showing proof of principle. With an acute reduction in circulatory volume (10-15%), pump flow immediately dropped from 4.1 to 1.9 l/min. Our pump control algorithm was able to restore bypass flow to 3.2 l/min (about 80% of the original level) and, thereby, reduced the duration of the low-flow condition. This demonstrates that a reserve-driven pump control strategy, based on the continuous monitoring of drainable volume, may maintain extracorporeal circulatory support flow, despite serious changes in filling conditions.


Inactivation of two haemolytic toxin genes in Aeromonas hydrophila attenuates virulence in a suckling mouse model.
The contribution of two unrelated Aeromonas hydrophila beta-haemolytic toxins to virulence was assessed in a suckling mouse model. The first haemolysin gene, isolated from an A. hydrophila A6 cosmid bank, encoded a potential gene product of 621 amino acids and a predicted molecular size of 69.0 kDa. The inferred amino acid sequence showed 89% identity to the AHH1 haemolysin of A. hydrophila ATCC 7966, and 51% identity to the HlyA haemolysin of Vibrio cholerae EI Tor strain O17. The second haemolysin gene (designated aerA), which encodes aerolysin, a pore-forming toxin, was partially cloned by PCR for the purpose of mutant construction. This PCR product was a 1040 bp fragment from the C-terminal region of aerA. It is proposed that the 69.0 kDa V. cholerae-HlyA-like haemolysin gene be termed hlyA to contrast with the aerA terminology for the aerolysin. A suicide vector was used to inactivate both the hlyA and aerA genes in A. hydrophila A6. When assessed in the suckling mouse model, only the hlyA aerA double mutant showed a statistically significant reduction in virulence--a 20-fold change in LD50 (Scheffe test, P < 0.05). Cytotoxicity to buffalo green monkey kidney cell monolayers and haemolysis on horse blood agar were eliminated only in the hlyA aerA double mutants. This is the first report of cloning and mutagenesis of two unrelated haemolytic toxin genes in the same strain of a mesophilic aeromonad. For A. hydrophila, a two-toxin model provides a more complete explanation of virulence.


A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer.
This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P=0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade≥3 AEs (experimental arm). Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity.


Immunohistochemistry-based subtyping of breast carcinoma in Egyptian women: a clinicopathologic study on 125 patients.
Breast carcinoma is a heterogeneous disease affected by patients' ethnicity. Gene expression analysis identified several molecular subtypes, and similar subtyping has now been found to be feasible using immunohistochemistry. This study estimated the distribution of intrinsic breast cancer subtypes using estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (Her2/neu), and cytokeratin 5/6 immunostaining in a cohort of 125 Egyptian women diagnosed as having invasive breast carcinoma. Associations with clinicopathologic variables and the prognostic markers Bcl-2 and Cyclin D1 were investigated and statistically analyzed. Population difference in breast cancer subtypes was detected, suggesting etiologic and genetic heterogeneity among demographic groups. As reported worldwide, most tumors were luminal A (39.2%), but basal-like and unclassified subtypes had higher proportions among our cohort (16.8% and 16%, respectively), particularly in premenopausal patients (P = .0001), in contrast to postmenopausal African Americans, premenopausal European Americans, and other populations. Her2-overexpressing subtype was the least common subtype (13.65%) among our patients, although it is more common in Asians. Basal-like and unclassified carcinomas were more frequently grade 3 neoplasms (P = .035). Lobular histology was distributed among luminal A, B and unclassified subtypes (P = .006). The highest frequency of nodal positivity was associated with Her2 overexpressing carcinomas (94.1%, P = .0001). Luminal and unclassified carcinomas more likely expressed Bcl-2 (P = .011) and Cyclin D1 (P = .0001), whereas basal and Her2 subtypes had the lowest expression levels. Immunohistochemistry-based subtyping can be helpful in separating breast carcinoma into subtypes that vary in distribution among different populations. These subtypes have distinct clinicopathologic features and diverse prognostication, which may imply different therapeutic options for each subtype.


[Detection of viral infection pathogens in medicinal plants grown in Ukraine].
Monitoring of viral infection on medicinal plant plantations is carried out. Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L. with symptoms of viral infection were revealed. Viral nature of symptoms was proved with biotesting method. Morphology and sizes of virus particles, detected in Panax ginseng method. Morphology and sizes of virus particles, detected in Panax ginseng C.A. Meyer, Valeriana officinalis L., Plantago major L., were determined with electron microscopy method. The paper is presented in Ukrainian.


Commentary on "The number of undocumented immigrants in the United States: Estimates based on demographic modeling with data from 1990-2016".
"The number of undocumented immigrants in the United States: Estimates based on demographic modeling with data from 1990-2016" by Fazel-Zarandi, Feinstein and Kaplan presents strikingly higher estimates of the unauthorized immigrant population than established estimates using the residual method. Fazel-Zarandi et. al.'s estimates range from a low or "conservative" number of 16.7 million unauthorized immigrants, to an "average" of 22.1 million, and to a high of 27.5 million. The Pew Hispanic Center estimated the population at 11.3 million in 2016, and the Department of Homeland Security (DHS) estimated it at 12.3 million. The new method shows much more rapid growth in unauthorized immigration during the 1990s and a substantially higher population in 2000 (13.3 million according to their "conservative" model) than Pew (8.6 million) and DHS (8.5 million). In this commentary, we explain that such an estimate for 2000 is implausible, as it suggests that the 2000 Census undercounted the unauthorized immigrant population by at least 42% in the 2000 Census, and it is misaligned with other demographic data. Fazel-Zarandi, Feinstein and Kaplan's model produces estimates that have a 10 million-person range in 2016, far too wide to be useful for public policy purposes; their estimates are not benchmarked against any external data sources; and their model appears to be driven by assumptions about return migration of unauthorized immigrants during the 1990s. Using emigration rates from the binational Mexican Migration Project survey for the illegal border-crosser portion of the unauthorized population, we generate a 2000 unauthorized population estimate of 8.2 million-slightly below Pew and DHS's estimates-without changing other assumptions in the model. We conclude that this new model's estimates are highly sensitive to assumptions about emigration, and moreover, that the knowledge base about emigration in the unauthorized population during the 1990s is not well enough developed to support the model underlying their estimates.


The Bam repeats of the mouse genome belong in several superfamilies the longest of which is over 9 kb in size.
Mouse DNA contains two equally abundant, homologous subfamilies of MspI 3.6 and 5 kb repeated fragments. The first subfamily corresponds to the previously described (1) Bam 4 kb repeats, the second one to Bam repeated fragments of higher molecular weight. These subfamilies account for the vast majority of long Bam repeats and are linked with contiguous short Bam 0.5 kb repeats. A minority of these composite Bam repeats extend, on the 0.5 kb side, into R repeats. In turn, a fraction of the composite Bam/R repeats extend further, for at least 3 kb, into other repeated sequences contiguous to the R repeats. The long Bam repeats belong, therefore, in at least three superfamilies of repeats, the longest one being over 9 kb in size. Some general properties of these superfamilies are discussed.


Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study.
This population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. The study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. A total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. In this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.


Campylobacter colitis: histological immunohistochemical and ultrastructural findings.
The colonic biopsy specimens of 22 patients with colitis and positive stool cultures for Campylobacter jejuni were studied in order to obtain histological and immunohistochemical criteria to differentiate Campylobacter colitis from chronic inflammatory bowel disease. In addition we tried to identify Campylobacter inclusions by means of immunohistochemistry and electron microscopy as evidence for invasion of the colonic mucosa. The results show that the majority of patients with Campylobacter colitis have the histological picture of acute infectious colitis with increased numbers of IgA and IgM containing plasma cells in the colonic mucosa in contrast with patients with active chronic inflammatory bowel disease who show increases of IgA and IgG (ulcerative colitis) or IgA-, IgM and IgG containing plasma cells (M Crohn) in their colonic biopsies. The results of immunohistochemical stainings with Campylobacter antiserum show invasion of Campylobacter in the colonic mucosa. These findings were confirmed ultrastructurally.


Compensatory Increase of Serum Hepassocin Protects Hyperthyroidism-Induced Hepatic Dysfunction.
Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of 36 subjects with Graves' disease were enrolled, and we found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin concentrations at 6 months after standard treatment for hyperthyroidism. In addition, HepG2 cell line was used to investigate the role of hepassocin in hyperthyroidism-induced hepatic dysfunction. Treatment of hepassocin recombinant protein in HepG2 cells dose-dependently decreased triiodothyronine (T3)-induced ALT and aspartate aminotransferase (AST) elevation. Moreover, hepassocin significantly increased the expression of phosphoenolpyruvate carboxykinase (PEPCK) in a dose-dependent manner. Deletion of hepassocin in HepG2 cells reversed the effects of T3 on PEPCK expressions. Furthermore, we found that T3 increased the expression of hepassocin through a hepatocyte nuclear factor 1α-dependent pathway. Taken together, these results indicated a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction.


Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapy.
Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification, and the homeostasis of self-renewing adult tissues. In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/β-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells, and discuss how harnessing the Wnt/β-catenin pathway might improve the efficacy of vaccines, T-cell-based therapies, and allogeneic stem cell transplantation for the treatment of patients with cancer.


Early developmental risks for tobacco addiction: A probabilistic epigenesis framework.
Considerable progress has been made in elucidating the relationships between early life psychobiological and environmental risk factors and the development of tobacco addiction. However, a comprehensive understanding of the heterogeneity in tobacco addiction phenotypes requires integrating research findings. The probabilistic epigenesis meta-theory offers a valuable framework for this integration, considering systemic, multilevel, developmental, and evolutionary perspectives. In this paper, we critically review relevant research on early developmental risks associated with tobacco addiction and highlight the integrative heuristic value of the probabilistic epigenesis framework for this research. For this, we propose a four-level systems approach as an initial step towards integration, analyzing complex interactions among different levels of influence. Additionally, we explore a coaction approach to examine key interactions between early risk factors. Moreover, we introduce developmental pathways to understand interindividual differences in tobacco addiction risk during development. This integrative approach holds promise for advancing our understanding of tobacco addiction etiology and informing potentially effective intervention strategies.


Antimicrobial, Antioxidant, Anti-Inflammatory, and Cytotoxic Activities of Propolis from the Stingless Bee Tetragonisca fiebrigi (Jataí).
Propolis from stingless bees Tetragonisca fiebrigi found in Brazil is used in folk medicine by their nutritional and therapeutic properties. However, there are no scientific records evidencing such properties. The present study was designed to investigate the chemical composition and the biological properties of propolis from T. fiebrigi. For this, the chemical composition of the ethanol extract of propolis (EEP) was determined by GC-MS and presented phenolic compounds, alcohol, and terpenes as its major class compounds. The antimicrobial activity was accessed in gram-positive and gram-negative bacteria and in fungi, isolated from different biological fluids and reference strains. The EEP was active against all microorganisms and showed antioxidant activity by scavenging free radicals, inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The anti-inflammatory potential of the EEP was confirmed by inhibition of the hyaluronidase enzyme. The cytotoxic activity was concentration-dependent against K562 cells, with a predominance of death by necrosis. Taken together, these results show that propolis from T. fiebrigi has important therapeutic activities, which suggest its potential application in the pharmaceutical industry, as well as in health foods, beverages, and nutritional supplements.


Impaired savings despite intact initial learning of motor adaptation in Parkinson's disease.
In motor adaptation, the occurrence of savings (faster relearning of a previously learned motor adaptation task) has been explained in terms of operant reinforcement learning (Huang et al. in Neuron 70(4):787-801, 2011), which is thought to associate an adapted motor command with outcome success during repeated execution of the adapted movement. There is some evidence for deficient savings in Parkinson's Disease (PD), which might result from deficient operant reinforcement processes. However, this evidence is compromised by limited adaptation training during initial learning and by multi-target adaptation, which reduces the number of reinforced movement repetitions for each target. Here, we examined savings in PD patients and controls following overlearning with a single target. PD patients showed less savings than controls after successive adaptation and deadaptation blocks within the same test session, as well as less savings across test sessions separated by a 24-h delay. It is argued that impaired blunted dopaminergic signals in PD impairs the modulation of dopaminergic signals to the motor cortex in response to rewarding motor outcomes, thus impairing the association of the adapted motor command with rewarding motor outcomes. Consequently, the previously adapted motor command is not preferentially selected during relearning, and savings is impaired.


Measuring Electrical Conductivity to Study the Formation of Brines Under Martian Conditions.
This paper describes a protocol to design experiments to study the formation of brines under Martian conditions and monitor the process with electrical conductivity measurements. We used the Engineering Qualification Model (EQM) of Habitability: Brines, Irradiation, and Temperature (HABIT)/ExoMars 2022 instrument for the experiment setup but we provide a brief account of constructing a simple and inexpensive electrical conductivity measurement setup. The protocol serves to calibrate the electrical conductivity measurements of the salt deliquescence into brine in a simulated Martian environment. The Martian conditions of temperature (-70 °C to 20 °C), relative humidity (0% to 100%) and pressure (7 - 8 mbar) with carbon-dioxide atmosphere were simulated in the SpaceQ Mars simulation chamber, a facility at the Luleå University of Technology, Sweden. The hydrate form of the known amount of salt accommodated between a pair of electrodes and thus the electrical conductivity measured depends predominantly on its water content and the temperature and relative humidity of the system. Electrical conductivity measurements were carried out at 1 Hz while exposing salts to a continuously increasing relative humidity (to force transitioning through various hydrates) at different Martian temperatures. For demonstration, a day-night cycle at Oxia Planum, Mars (the landing site of ExoMars 2022 mission) was recreated.


A psychological and neuroanatomical model of obsessive-compulsive disorder.
Imaging, surgical, and lesion studies suggest that the prefrontal cortex (orbitofrontal and anterior cingulate cortexes), basal ganglia, and thalamus are involved in the pathogenesis of obsessive-compulsive disorder (OCD). On the basis of these findings several models of OCD have been developed, but have had difficulty fully integrating the psychological and neuroanatomical findings of OCD. Recent research in the field of cognitive neuroscience on the normal function of these brain areas demonstrates the role of the orbitofrontal cortex in reward, the anterior cingulate cortex in error detection, the basal ganglia in affecting the threshold for activation of motor and behavioral programs, and the prefrontal cortex in storing memories of behavioral sequences (called "structured event complexes" or SECs). The authors propose that the initiation of these SECs can be accompanied by anxiety that is relieved with completion of the SEC, and that a deficit in this process could be responsible for many of the symptoms of OCD. Specifically, the anxiety can form the basis of an obsession, and a compulsion can be an attempt to receive relief from the anxiety by repeating parts of, or an entire, SEC. The authors discuss empiric support for, and specific experimental predictions of, this model. The authors believe that this model explains the specific symptoms, and integrates the psychology and neuroanatomy of OCD better than previous models.


Beggiatoa: occurrence in the rice rhizosphere.
A catalase-like activity surrounding the root tips of rice plants favors the presence of Beggiatoa, an organism capable of oxidizing the hydrogen sulfide which is toxic to rice and is found in paddy soil conditions. Beggiatoa has now been isolated from rice field soil. A mutually favorable interaction between rice and this bacterium is suggested.


Selection of nectar plants for use in ecological engineering to promote biological control of rice pests by the predatory bug, Cyrtorhinus lividipennis, (Heteroptera: Miridae).
Ecological engineering for pest management involves the identification of optimal forms of botanical diversity to incorporate into a farming system to suppress pests, by promoting their natural enemies. Whilst this approach has been extensively researched in many temperate crop systems, much less has been done for rice. This paper reports the influence of various plant species on the performance of a key natural enemy of rice planthopper pests, the predatory mirid bug, Cyrtorhinus lividipennis. Survival of adult males and females was increased by the presence of flowering Tagetes erecta, Trida procumbens, Emilia sonchifolia (Compositae), and Sesamum indicum (Pedaliaceae) compared with water or nil controls. All flower treatments resulted in increased consumption of brown plant hopper, Nilaparvata lugens, and for female C. lividipennis, S. indicum was the most favorable. A separate study with a wider range of plant species and varying densities of prey eggs showed that S. indicum most strongly promoted predation by C. lividipennis. Reflecting this, S. indicum gave a relatively high rate of prey search and low prey handling time. On this basis, S. indicum was selected for more detailed studies to check if its potential incorporation into the farming system would not inadvertently benefit Cnaphalocrocis medinalis and Marasmia patnalis, serious Lepidoptera pests of rice. Adult longevity and fecundity of both pests was comparable for S. indicum and water treatments and significantly lower than the honey solution treatment. Findings indicate that S. indicumis well suited for use as an ecological engineering plant in the margins of rice crops. Sesame indicum can be a valuable crop as well as providing benefits to C. lividipennis whilst denying benefit to key pests.


Analysis of leakage in IRGA's leaf chambers of open gas exchange systems: quantification and its effects in photosynthesis parameterization.
The measurement of the response of net photosynthesis to leaf internal CO2 (i.e. A-Ci curves) is widely used for ecophysiological studies. Most studies did not consider CO2 exchange between the chamber and the surrounding air, especially at the two extremes of A-Ci curves, where large CO2 gradients are created, leading to erroneous estimations of A and Ci. A quantitative analysis of CO2 leakage in the chamber of a portable open gas exchange system (Li-6400, LI-COR Inc., NE, USA) was performed. In an empty chamber, the measured CO2 leakage was similar to that calculated using the manufacturer's equations. However, in the presence of a photosynthetically inactive leaf, the magnitude of leakage was substantially decreased, although still significant. These results, together with the analysis of the effects of chamber size, tightness, flow rate, and gasket material, suggest that the leakage is larger at the interface between the gaskets than through the gaskets. This differential leakage rate affects the parameterization by photosynthesis models. The magnitude of these errors was assessed in tobacco plants. The results showed that leakage results in a 10% overestimation of the leaf maximum capacity for carboxylation (Vc,max) and a 40% overestimation of day respiration (Rl). Using the manufacturer's equations resulted in larger, non-realistic corrections of the true values. The photosynthetic response to CO2 concentrations at the chloroplast (i.e. A-Cc curves) was significantly less affected by leakage than A-Ci curves. Therefore, photosynthetic parameterization can be improved by: (i) correcting A and Ci values for chamber leakage estimated using a photosynthetically inactive leaf; and (ii) using A-Cc instead of A-Ci curves.


Boundary detection in multidimensions.
The development of image processing algorithms for time-varying imagery and computerized tomography data calls for generalization of the concepts of adjacency, connectivity, boundary, etc., to three and four-dimensional discrete spaces. This paper defines these basic concepts in unified terminology and presents algorithms for a boundary detection task in multidimensional space. The performance of these algorithms is discussed with respect to theoretical maximum complexity, and is illustrated with simulated computerized tomography data.


Participation of calcium and calmodulin in the formation of acetylcholine receptor clusters.
The formation of acetylcholine receptor (AChR) clusters can be experimentally induced in cultured Xenopus myotomal muscle cells by positive polypeptide-coated latex beads (Peng, H.B., P.-C. Cheng, and P.W. Luther, 1981, Nature [Lond.], 292:831-834). This provides a simple procedure for studying the cellular process of AChR clustering. In this study, the involvement of calcium and calmodulin in this process was examined. A deprivation in extracellular calcium by calcium-free medium or by the addition of calcium antagonists such as divalent cations Co2+ and Ni2+ (1-5 mM) or organic compounds verapamil and D-600 (0.1-0.5 mM) suppressed the formation of AChR clusters induced by the latex beads in a largely reversible manner. Antagonists against calmodulin, including trifluoperazine (1-5 microM) and the naphthalene sulfonamide W-7 (20 microM), also suppressed AChR clustering. However, the effect of W-7 was much weaker than that of trifluoperazine (TFP). Although the formation of AChR clusters is inhibited by these drugs, the stability of the existent clusters is relatively insensitive to them. These data suggest that the clustering of AChR involves a Ca2+ and calmodulin-activated process. Immunofluorescence studies using an antibody against calmodulin indicate that calmodulin is diffusely distributed in the cytoplasm in addition to its localization at the I-bands. Thus I propose that a local rise in intracellular calcium caused by a locally applied stimulus, exemplified here by the polypeptide-coated latex beads, may trigger the formation of AChR clusters. Furthermore, the cellular machinery for this process may involve calmodulin and is diffusely distributed in the muscle cell.


Cortical Representation of Touch in Silico.
With its six layers and ~ 12,000 neurons, a cortical column is a complex network whose function is plausibly greater than the sum of its constituents'. Functional characterization of its network components will require going beyond the brute-force modulation of the neural activity of a small group of neurons. Here we introduce an open-source, biologically inspired, computationally efficient network model of the somatosensory cortex's granular and supragranular layers after reconstructing the barrel cortex in soma resolution. Comparisons of the network activity to empirical observations showed that the in silico network replicates the known properties of touch representations and whisker deprivation-induced changes in synaptic strength induced in vivo. Simulations show that the history of the membrane potential acts as a spatial filter that determines the presynaptic population of neurons contributing to a post-synaptic action potential; this spatial filtering might be critical for synaptic integration of top-down and bottom-up information.


NF-kappaB and AP-1 regulate activation-dependent CD137 (4-1BB) expression in T cells.
4-1BB(CD137) is a member of the tumor necrosis factor receptor superfamily and provides a costimulatory signal by interaction with 4-1BB ligand expressed on antigen-presenting cells. The expression of 4-1BB is known to be activation-dependent. Here, we investigated the transcriptional machinery required for T cell receptor (TCR) activation-dependent induction of 4-1BB expression in CD3-CEM cells treated with phorbol myristate acetate and ionomycin. Using 5'-deletion constructs of 4-1BB promoter in luciferase reporter assays, we demonstrated that the transcriptional elements mediating 4-1BB upregulation were located in the region between approximately 0.9 and approximately 1.1 kb from the translational start site. Characterization of these sites by electrophoretic mobility shift assay and site-directed mutagenesis revealed that nuclear factor kappaB (NF-kappaB) and activating protein-1 (AP-1) are involved. MEK and c-Jun N-terminal kinase-1 activity was required for activation-dependent 4-1BB upregulation. Thus, NF-kappaB and AP-1 are involved in the TCR stimulation-dependent transcriptional regulation of the 4-1BB promoter.


Enhanced cellular uptake of antisecretory peptide AF-16 through proteoglycan binding.
Peptide AF-16, which includes the active site of Antisecretory Factor protein, has antisecretory and anti-inflammatory properties, making it a potent drug candidate for treatment of secretory and inflammatory diseases such as diarrhea, inflammatory bowel diseases, and intracranial hypertension. Despite remarkable physiological effects and great pharmaceutical need for drug discovery, very little is yet understood about AF-16 mechanism of action. In order to address interaction mechanisms, we investigated the binding of AF-16 to sulfated glycosaminoglycan, heparin, with focus on the effect of pH and ionic strength, and studied the influence of cell-surface proteoglycans on cellular uptake efficiency. Confocal laser scanning microscopy and flow cytometry experiments on wild type and proteoglycan-deficient Chinese hamster ovary cells reveal an endocytotic nature of AF-16 cellular uptake that is, however, less efficient for the cells lacking cell-surface proteoglycans. Isothermal titration calorimetry provides quantitative thermodynamic data and evidence for that the peptide affinity to heparin increases at lower pH and ionic strength. Experimental data, supported by theoretical modeling, of peptide-glycosaminoglycan interaction indicate that it has a large electrostatic contribution, which will be enhanced in diseases accompanied by decreased pH and ionic strength. These observations show that cell-surface proteoglycans are of general and crucial importance for the antisecretory and anti-inflammatory activities of AF-16.


Survey of Clinician Opinions on Kidney Transplantation from Hepatitis C Virus Positive Donors: Identifying and Overcoming Barriers.
Transplant practices related to use of organs from Hepatitis C virus infected donors (DHCV+) is evolving rapidly. We surveyed U.S. kidney transplant programs by email and professional society listserv postings between 7/19-1/20 to assess attitudes, management strategies, and barriers related to use of viremic (nucleic acid testing (NAT)+) donor organs in HCV uninfected recipients. Staff at 112 unique programs responded, representing 54% of U.S. adult kidney transplant programs and 69% of adult deceased donor kidney transplant volume in 2019. Most survey respondents were transplant nephrologists (46%) or surgeons (43%). Among responding programs, 67% currently transplant DHCV antibody+/NAT- organs under a clinical protocol or as standard of care. By comparison, only 58% offer DHCV NAT+ kidney transplant to HCV- recipients, including 35% under clinical protocols, 14% as standard of care, and 9% under research protocols. Following transplant of DHCV NAT+ organs to uninfected recipients, 53% start direct acting antiviral agent (DAA) therapy after discharge and documented viremia. Viral monitoring protocols after DHCV NAT+ to HCV uninfected recipient kidney transplantation varied substantially. 56% of programs performing these transplants report having an institutional plan to provide DAA treatment if declined by the recipient's insurance. Respondents felt a mean decrease in waiting time of ≥18 months (range 0-60) justifies the practice. Program concerns related to use of DHCV NAT+ kidneys include insurance coverage concerns (72%), cost (60%), and perceived risk of transmitting resistant infection (44%). Addressing knowledge about safety and logistical/financial barriers related to use of DHCV NAT+ kidney transplantation for HCV uninfected recipients may help reduced discards and expand the organ supply.


Patient geometry-driven information retrieval for IMRT treatment plan quality control.
Intensity modulated radiation therapy (IMRT) treatment plan quality depends on the planner's level of experience and the amount of time the planner invests in developing the plan. Planners often unwittingly accept plans when further sparing of the organs at risk (OARs) is possible. The authors propose a method of IMRT treatment plan quality control that helps planners to evaluate the doses of the OARs upon completion of a new plan. It is achieved by comparing the geometric configurations of the OARs and targets of a new patient with those of prior patients, whose plans are maintained in a database. They introduce the concept of a shape relationship descriptor and, specifically, the overlap volume histogram (OVH) to describe the spatial configuration of an OAR with respect to a target. The OVH provides a way to infer the likely DVHs of the OARs by comparing the relative spatial configurations between patients. A database of prior patients is built to serve as an external reference. At the conclusion of a new plan, planners search through the database and identify related patients by comparing the OAR-target geometric relationships of the new patient with those of prior patients. The treatment plans of these related patients are retrieved from the database and guide planners in determining whether lower doses delivered to the OARs in the new plan are feasible. Preliminary evaluation is promising. In this evaluation, they applied the analysis to the parotid DVHs of 32 prior head-and-neck patients, whose plans are maintained in a database. Each parotid was queried against the other 63 parotids to determine whether a lower dose was possible. The 17 parotids that promised the greatest reduction in D50 (DVH dose at 50% volume) were flagged. These 17 parotids came from 13 patients. The method also indicated that the doses of the other nine parotids of the 13 patients could not be reduced, so they were included in the replanning process as controls. Replanning with an effort to reduce D50 was conducted on these 26 parotids. After replanning, the average reductions for D50 of the 17 flagged parotids and nine unflagged parotids were 6.6 and 1.9 Gy, respectively. These results demonstrate that the quality control method has accurately identified not only the parotids that require dose reductions but also those for which dose reductions are marginal. Originally, 11 of out the 17 flagged parotids did not meet the Radiation Therapy Oncology Group sparing goal of V(30 Gy) < 50%. Replanning reduced them to three. Additionally, PTV coverage and OAR sparing of the original plans were compared to those of the replans by using pairwise Wilcoxon p test. The statistical comparisons show that replanning compromised neither PTV coverage nor OAR sparing. This method provides an effective quality control mechanism for evaluating the DVHs of the OARs. Adoption of such a method will advance the quality of current IMRT planning, providing better treatment plan consistency.


Tick-Tattoo: DNA Vaccination Against B. burgdorferi or Ixodes scapularis Tick Proteins.
Borrelia burgdorferi sensu lato (sl) is the causative agent of Lyme borreliosis. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines. DNA tattoo vaccination with B. afzelii strain PKo OspC in mice has proven to be fully protective against B. afzelii syringe challenge and induces a favorable humoral immunity compared to recombinant protein vaccination. Alternatively, several recombinant protein vaccines based on tick proteins have shown promising effect in tick-bite infection models. In this study, we evaluated the efficacy of DNA vaccines against Borrelia OspC or tick antigens in a tick-bite infection model. We vaccinated C3H/HeN mice with OspC using a codon-optimized DNA vaccine or with recombinant protein. We challenged these mice with B. burgdorferi sensu stricto (ss)-infected Ixodes scapularis nymphs. Subsequently, we vaccinated C3H/HeN mice with DNA vaccines coding for tick proteins for which recombinant protein vaccines have previously resulted in interference with tick feeding and/or Borrelia transmission: Salp15, tHRF, TSLPI, and Tix-5. These mice were also challenged with B. burgdorferi ss infected Ixodes scapularis nymphs. DNA tattoo and recombinant OspC vaccination both induced total IgG responses. Borrelia cultures and DNA loads of skin and bladder remained negative in the mice vaccinated with OspC DNA vaccination, except for one culture. DNA vaccines against tick antigens Salp15 and Tix-5 induced IgG responses, while those against tHRF and TSLPI barely induced any IgG response. In addition, Borrelia cultures, and DNA loads from mice tattooed with DNA vaccines against tick proteins TSLPI, Salp15, tHRF, and Tix-5 were all positive. A DNA tattoo vaccine against OspC induced high specific IgG titers and provided near total protection against B. burgdorferi ss infection by tick challenge. In contrast, DNA tattoo vaccines against tick proteins TSLPI, Salp15, tHRF, and Tix-5 induced low to moderate IgG titers and did not provide protection. Therefore, DNA tattoo vaccination does not seem a suitable vaccine strategy to identify, or screen for, tick antigens for anti-tick vaccines. However, DNA tattoo vaccination is a straightforward and effective vaccination platform to assess novel B. burgdorferi sl antigen candidates in a relevant tick challenge model.


Regulation of tissue inhibitor of metalloproteinase 1 gene transcription by RUNX1 and RUNX2.
Tissue inhibitor of metalloproteinase 1 (TIMP1) is a contributory factor to fibrosis of a variety of organs including the liver. UTE-1 is a regulatory DNA motif essential for TIMP1 promoter activity in a variety of cell types including hepatic stellate cells (HSC), the key profibrogenic cells of the liver. In this study we identify RUNX1 and RUNX2 as UTE-1-binding proteins that are induced at the post-transcriptional level during activation of HSC. RUNX1 is expressed in at least two major isoforms, RUNX1B and RUNX1A. Overexpression of full-length RUNX1B isoform in HSC repressed TIMP1 promoter activity, whereas the truncated RUNX1A isoform and RUNX2 functioned as stimulators. To gain further understanding of the way in which RUNX1 isoforms differentially regulate TIMP1 transcription, we investigated the relationship between the UTE-1 site and its adjacent upstream serum-response element (SRE) in the promoter. The UTE-1 and SRE sites cooperate in a synergistic fashion to stimulate transcription of a heterologous minimal active promoter providing that they are in close proximity. The key regulatory sequence within the SRE is an AP-1 site that in HSC directs high level transcription via its interaction with JunD. RUNX1A was shown to interact directly with JunD, and by contrast RUNX1B failed to interact with JunD. Co-expression studies showed that RUNX1B can repress JunD-stimulated TIMP1 promoter activity. From these observations we propose that JunD and RUNX factors assemble at the adjacent SRE and UTE-1 sites in the TIMP1 promoter and form functional interactions that stimulate transcription. However, RUNX1B is unable to interact with JunD, and as such its occupancy at the UTE-1 site disrupts the optimal assembly of transcriptional activators required for directing high level TIMP1 promoter function.


Ultrasensitive size-selection of plasmonic nanoparticles by Fano interference optical force.
In this paper, we propose a solution for the ultrasensitive optical selection of plasmonic nanoparticles using Fano interference-induced scattering forces. Under a Gaussian beam excitation, the scattering of a plasmonic nanoparticle at its Fano resonance becomes strongly asymmetric in the lateral direction and consequently results in a net transverse scattering force, that is, Fano interference-induced force. The magnitude of this transverse scattering force is comparable with the gradient force in conventional optical manipulation experiments. More interestingly, the Fano scattering force is ultrasensitive to the particle size and excitation frequency due to the phase sensitivity of the interference between adjacent plasmon modes in the particle. Utilizing this distinct feature, we show the possibility of size-selective sorting of silver and gold nanoparticles with an accuracy of about ±10 nm and silica-gold core-shell nanoparticles with shell thickness down to several nanometers. These results would add to the toolbox of optical manipulation and fabrication.


A hidden cost of happiness in children.
Happiness is generally considered an emotion with only beneficial effects, particularly in childhood. However, there are some situations where the style of information processing triggered by happiness could be a liability. In particular, happiness seems to motivate a top-down processing style, which could impair performance when attention to detail is required. Indeed, in Experiment 1, 10- to 11-year-old children (N = 30) induced to feel a happy mood were slower to locate a simple shape embedded in a complex figure than those induced to feel a sad mood. In Experiment 2, 6- to 7-year-old children (N = 61) induced to feel a happy mood found fewer embedded shapes than those induced to feel a sad or neutral mood. Happiness may have unintended and possibly undesirable cognitive consequences, even in childhood.


Effect of eccentric strengthening after anterior cruciate ligament reconstruction on quadriceps strength.
Interventions aimed at safely overloading the quadriceps muscle after anterior cruciate ligament (ACL) reconstruction are essential to reducing quadriceps muscle weakness that often persists long after the rehabilitation period. Despite the best efforts of clinicians and researchers to improve ACL rehabilitation techniques, a universally effective intervention to restore preinjury quadriceps strength has yet to be identified. A muscle's force-producing capacity is most optimal when an external force exceeds that of the muscle while the muscle lengthens. Hence, the potential to improve muscle strength by overloading the tissue is greater with eccentric strengthening than with concentric strengthening. Traditionally, the application of early postoperative high-intensity eccentric resistance training to the ACL-reconstructed limb has been contraindicated, as there is potential for injury to the ACL graft, articular cartilage, or surrounding soft-tissue structures. However, recent evidence suggests that the application of early, progressive, high-force eccentric resistance exercises to the involved limb can be used to safely increase muscle volume and strength in ACL-reconstructed individuals. As a result, eccentric strengthening may be another attractive alternative to traditional concentric strengthening to improve quadriceps strength after ACL reconstruction. In patients who have undergone ACL reconstruction, is there evidence to suggest that eccentric exercise positively affects postoperative quadriceps strength?