Comparison of the Microgenics CEDIA heroin metabolite (6-AM) and the Roche Abuscreen ONLINE opiate immunoassays for the detection of heroin use in forensic urine samples.
Current Department of Defense (DoD) and Department of Health and Human Services (HHS) procedures for the detection of heroin abuse by testing urine utilize an initial opiate (codeine/morphine) immunoassay (IA) screen followed by gas chromatography-mass spectrometry (GC-MS) confirmation of 6-acetylmorphine (6-AM), if the morphine concentration is above established cutoff. An alternative to the current opiates screen for heroin abuse is the direct IA for the metabolite of heroin, 6-acetylmorphine. In this regard, the performance of the Microgenics CEDIA heroin metabolite (6-AM) screening reagent was assessed. This evaluation was conducted on the P module of a Hitachi Modular automated IA analyzer calibrated using 6-AM at 10 ng/mL. Reproducibility, linearity, accuracy, sensitivity, and interferences associated with use of the 6-AM IA reagent were evaluated. The IA reagent precision (percent coefficient of variation (%CV)) around each of seven standards was less than 0.63%, with a linearity (r(2)) value of 0.9951. A total of 37,713 active duty service members' urine samples were analyzed simultaneously using the CEDIA heroin metabolite (6-AM) reagent and the Roche Abuscreen ONLINE opiate reagent to evaluate both the prevalence rate of 6-AM in the demographic group and the sensitivity and specificity of the reagents for the detection of heroin use. Of the 37,713 samples tested using the CEDIA heroin metabolite (6-AM) reagent, three samples screened positive at the DoD and HHS cutoff of 10 ng/mL. One of the three samples confirmed positive for 6-AM by GC-MS above the cutoff of 10 ng/mL, the two remaining samples confirmed negative for 6-AM at a GC-MS limit of detection (LOD) of 2.1 ng/mL. In contrast, the Roche Abuscreen ONLINE opiate IA produced 74 opiate-positive results for codeine/morphine, with 6 of the 74 specimens confirming positive for morphine above the DoD cutoff concentration of 4000 ng/mL (8% DoD morphine confirmation rate), only one of the 74 opiate-positive screen specimens confirmed positive for 6-AM above the 10 ng/mL GC-MS cutoff concentration. As a further check of the sensitivity and specificity of the Microgenics 6-AM IA reagent, human urine samples (n = 87) known to contain 6-AM by GC-MS, were re-analyzed using both IA reagents. All 87 of the samples screened positive using the CEDIA heroin metabolite (6-AM) assay. However, using the Roche ONLINE opiate reagent, 12 of the known 6-AM positives screened negative at the DoD and HHS screening cutoff of 2000 ng/mL (morphine). Of the remaining 75 samples that screened positive by the ONLINE opiate reagent, five of the samples did not contain morphine above the DoD GC-MS cutoff concentration of 4000 ng/mL and would not have required 6-AM analysis. However, under the HHS GC-MS morphine cutoff concentration of 2000 ng/mL all 75 samples would have required 6-AM analysis. Furthermore, using the current DoD opiate screen, 17 out of 87 samples known to contain 6-AM would have gone undetected (19.5% false-negative rate); additionally, even under the more stringent HHS opiate screening standards 12 out of the 87 samples known to contain 6-AM would also have gone undetected (13.8% false-negative rate). The Microgenics CEDIA heroin metabolite (6-AM) reagent assay appears well adapted for the rapid and specific detection of heroin abuse as an alternative for, or an adjunct test to, the current opiates (codeine/morphine) IA screening procedure.


Concerted action of tenascin-C domains in cell adhesion, anti-adhesion and promotion of neurite outgrowth.
We used a new approach to identify domains of chicken tenascin-C required for interaction with cells. Instead of expressing the parts of interest, we deleted them from an otherwise intact tenascin-C molecule and scored for the concomitant change in activity. As a starting point for all mutant constructs we expressed the smallest naturally occurring tenascin-C splice variant in vertebrate cells. The tenascin-C mutants had either deletions of all EGF-like repeats, all fibronectin type III repeats or of the fibrinogen globe. In double mutants the fibronectin type III repeats were deleted together with either the EGF-like repeats or the fibrinogen globe, respectively. All tenascin-C variants assembled correctly to hexameric molecules of the expected molecular characteristics. Intact tenascin-C and the mutant missing the fibrinogen globe did not promote adhesion of chick embryo fibroblasts, whereas both, the hexamers containing solely the fibrinogen globe or the EGF-like repeats were adhesive substrates and even supported cell spreading. When tenascin-C was added to the medium of fibroblasts plated on fibronectin-coated wells, cell adhesion was blocked by intact tenascin-C, but not by mutants missing the fibrinogen globe. In neurite outgrowth assays using dorsal root ganglia, processes formed on all substrates except on the mutant missing only the fibrinogen globe, where the ganglia failed to adhere. The mutants missing the fibronectin type III repeats allowed more rapid neurite outgrowth than all other tenascin-C variants and the mutant consisting essentially of oligomerized EGF-like repeats was as active a substrate for neurite outgrowth as laminin. From the combined data, it is concluded that the activities of intact tenascin-C cannot be mimicked by investigating domain by domain, but the concerted action of several domains leads to the diverse cellular responses.


Population structure of Serpula lacrymans in Europe with an outlook to the French population.
In this study the genetic variation and population structure in a French population of the dry rot fungus S. lacrymans was investigated using 14 microsatellites markers and compared to the rest of Europe. In that comparison the French population possessed the same allelic diversity as rest of Europe. A weak geographic structuring of the genetic variation was observed across Europe, where the French isolates to some extent separated from the rest of Europe, indicating that weak barriers to gene flow exists. Eighty percent of the isolates had unique multilocus microsatellite genotypes, which corresponds to high recombination and dispersal by sexual spores. Deviations from Hardy-Weinberg expectations were observed in multiple loci. In most loci there was an excess of heterozygotes, which could be due to either non-random mating, presence of more than two nuclei in the secondary mycelia or another unrecognized process. A total of six vegetative compatibility (VC) groups were present in Europe, out of which four were sampled in France. One VC group was over-represented in France while two others were underrepresented, as compared to the rest of Europe.


Beauty and the reef: Evaluating the use of non-expert ratings for monitoring aesthetic values of coral reefs.
Aesthetic values are a key driver of tourist and recreational visitation to natural areas and are listed among the selection criteria for World Heritage properties. However, assessment and monitoring of aesthetic values in natural areas, and coral reefs in particular, have proven to be challenging. In our study we explored the value and limitations of a rapid assessment approach involving non-expert ratings of aesthetic beauty as a potential tool for long-term monitoring of aesthetic values in the Great Barrier Reef World Heritage Area, Australia. We investigated the sensitivity of a rating scale for detecting change and sampling requirements for monitoring, as well as observer biases, using an online survey of 1417 Australians in which respondents rated the aesthetic beauty of 181 coral reef images on a ten-point scale. Our results show average aesthetic rating scores ranged from 4.35 to 8.34 on a scale from 1 (ugly) to 10 (beautiful), with potential to detect differences of statistical significance within one point, indicating sufficient sensitivity to change for monitoring purposes. We found that a sample size of c.100 ratings per image provided a reasonable balance between cost (i.e. sample size) and accuracy (i.e. error). Older respondents (>65 years) with higher levels of coral reef visitation, experience and interest were more likely to give extreme ratings, however, there was no apparent predictor for this bias to be positive or negative (high or low ratings). Based on these results we provide recommendations to assist coral reef managers in their use and interpretation of non-expert aesthetic ratings in coral reef monitoring.


The prognostic impact of preoperative mean corpuscular volume in colorectal cancer.
The relationship between preoperative mean corpuscular volume and postoperative prognosis has been reported in some cancers recently, but no certain consensus has been reached, especially for colorectal cancer. We evaluated the usefulness of mean corpuscular volume as a prognostic factor in colorectal cancer patients. This study included 1003 patients with colorectal cancer who underwent curative surgery in a single institution. The relationship between mean corpuscular volume values and postoperative recurrence was evaluated by fractional polynomial model. Based on the result, patients were divided into groups according to mean corpuscular volume values. Clinicopathological factors and long-term outcomes were compared between the groups. The risk of postoperative recurrence according to mean corpuscular volume value showed a J-shaped curve, suggesting that both low and high mean corpuscular volume have high risk. Low mean corpuscular volume (≤84 fl) group was oncologically advanced in terms of pathological tumor stage, histological grade and lymphatic invasion with higher inflammation markers. High mean corpuscular volume (>95 fl) group had higher frequency of drinking habit with higher values of aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase. Abnormal mean corpuscular volume group including these two groups showed significantly worse disease-free survival than the other (P < 0.001). Multivariate analysis suggested that abnormal mean corpuscular volume was an independent risk factor for postoperative recurrence (hazard ratio, 1.344; 95% confidence interval, 1.005-1.796; P = 0.046). Furthermore, its prognostic impact was more significant in pStage III than in other stages. Preoperative low and high mean corpuscular volume is a poor prognostic factor in colorectal cancer patients. It could be a predictive marker to estimate worse survival outcome after surgery.


Future vehicles: the effect of seat configuration on posture and quality of conversation.
The percentage of passengers that prefer travelling in groups is increasing. In most vehicles, passengers sit side by side and need to turn their body to be engaged in the conversation with their fellow travellers. However, rotating the body could lead to discomfort which influences conversation quality. The aim of this research is to study the effect of seat configuration on the (dis)comfort experience, conversation quality and posture. Experiments in which participants were asked to talk to each other while sitting at the same distance (1 m) were conducted in four seating arrangements (with seat-belts on), where the angle between the forward directions of two seats were positioned at 0° (side by side), 22.5°, 90° and 120° (almost opposite each other), respectively. Optical tracking has been deployed and the collected data were processed with MatLab® to acquire postural angles over time. Questionnaires were also used to evaluate the perceived (dis)comfort and the quality of the conversation. Experiment results indicate that the 120° configuration scored the best in the overall comfort and the quality of conversation, but only slightly better than the 90° configuration. Practitioner summary: Seating side by side is not optimal to have a comfortable conversation with your seatmate. To improve comfort and quality of conversation in future vehicles, we tested four seating arrangements analysing the effect of seat layout on (dis)comfort experience. Statistical analysis of objective and subjective data shows the optimal configuration for a comfortable conversation. Abbreviation: LPD: localized postural discomfort; PDF: probability density function; OCRA: occupational repetitive action.


Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti-cyclic citrullinated peptide antibody.
To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels among patients with rheumatoid arthritis (RA). The study sample included 66 RA patients who completed double-blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti-CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels. Patients had a mean +/- SD age of 49.9 +/- 12.0 years and were predominantly female (n = 51; 77%). The mean +/- SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 +/- 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a > or =25% reduction in the anti-CCP antibody level during the course of treatment, and 35 patients (55%) had a > or =25% reduction in RF. After adjustment for the baseline anti-CCP antibody level, only a shorter disease duration (< or =12 months) was significantly associated with a decline in the level of anti-CCP antibody (OR 3.0, 95% CI 1.0-8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2-10.4). Shorter disease duration predicts greater declines in anti-CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti-CCP antibody level.


Sex hormone-binding globulin and risk of clinical diabetes in American black, Hispanic, and Asian/Pacific Islander postmenopausal women.
Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations. We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians). Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09-0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10-0.38) for blacks; RR, 0.17 (95% CI, 0.05-0.57) for Hispanics; and 0.13 (95% CI, 0.03-0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07-0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14-0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RR(per SD) = 0.42, 95% CI, 0.34-0.51; past users: RR(per SD) = 0.53;, 95% CI, 0.37-0.77; current users: RR(per SD) = 0.57; 95% CI, 0.46-0.69; P-interaction = 0.10). In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance.


[Coagulation-inhibiting proteins; implications for cerebrovascular disorders].
Deficiencies in ATIII, PC, and PS are associated with a higher incidence of thromboembolic events. An analysis was made of these three proteins in 239 cases of non-embolic stroke; the incidence of their deficiency and the presence of intersexual variations were evaluated. Two different methods were used to measure PS, functional PS and free PS, comparing the values and the incidence of the deficiency. ATIII, PC, free PS, and functional PS deficiencies were found in 2.93%, 7.5%, 9.52% and 13.72%, respectively. The observed PS values showed statistically significant differences between sexes. There was a higher incidence of PS and PC deficiencies in patients with stroke, which were associated with a poorer prognosis. PS differed between sexes and both methods were valid for its quantitation.


Physiology and pathology of the oesophagus in the elderly patient.
In the 1960s, the term 'presbyoesophagus' was introduced for what were felt to be the characteristics of the oesophagus in old age. Since then a number of sophisticated studies using modern manometric, radiological, pH-metric or endoscopic equipment have been performed to better study this subject. Although results in some aspects are still contradictory, these studies have provided us with some more detailed information on the physiology of the ageing oesophagus. Beginning with an overview of what is currently known and discussed about age-induced physiological changes in oesophageal function, this review will then focus on specific problems of oesophagus-related diseases in the elderly. The main topics discussed will include presentation, diagnosis and treatment of primary and secondary motility disorders, oesophageal manifestations of neuromuscular and neurological disease, gastro-oesophageal reflux disease and oesophageal cancer in the elderly.


Prevalence and genotypes of human papillomavirus among Thai women.
One of the most common cancers in women worldwide is cervical cancer, with death rates highest in less developed countries, including Thailand. This study was conducted to explore the prevalence of human papillomavirus (HPV) and its related cytological abnormalities among women attending cervical screening clinics in Thailand using the polymerase chain reaction (PCR). LBC specimens (ThinPrep, Hologic, West Sussex, UK) were subjected to PCR of the E1 region to identify the most prevalent HPV types. Information on age and cytology grade was also collected. Among a total of 1,662 women, 29 different HPV types were found and the overall HPV prevalence was 8.7%. HPV prevalence among the general population amounted to 7.8%. The following HPV types were identified: HPV16 (17.9%), HPV90 (16.6%) and HPV71 (10.3%). The rates of other types were as follows; HPV66 (6.9%), HPV52 (6.2%), HPV34 (5.5%), HPV31 (5.3%), HPV42 (4.8%) and HPV39 (3.4%). HPV infection peaked in women aged around 20-39 years and thereafter gradually declined. As expected, HPV DNA can be found in normal cytology specimens. These results which elucidate HPV distribution in Thailand could be useful for vaccine development and the national cervical cancer prevention program.


Deception of cycling distance on pacing strategies, perceptual responses, and neural activity.
Pacing during exercise performance is well-established; however, little is known about the neural responses associated with changes in power output and the effect of exercise end-point knowledge. Therefore, the aim of this study was to examine the effect of deception of cycling distance on pacing, cerebral oxy- (O2Hb) and deoxy-haemoglobin concentrations, and alpha (α) wave activity. Ten well-trained male cyclists (23.7 ± 6.6 years) completed three cycling time trials (TT) on a stationary air-braked cycle ergometer and were informed the study was to examine the reliability of 3 × 30-km TT. Participants unknowingly completed three distances (24, 30, and 36 km) in a randomised order. Performance (power output; PO), physiological (heart rate; HR), perceptual (rating of perceived exertion; RPE), and neurological (O2Hb, HHb, and α activity) measures were recorded throughout each TT. Data were converted to a percentage relative to the total distance covered. At 100% completion, HR and PO were lower during the 36 km compared to the 30 km trial (P ≤ 0.01). Compared to the 24 km trial, α waves were reduced at 100% (effect size; ES = 1.01), while O2Hb was greater at 70% of completion in the 36 km trial (ES = 1.39). RPE was also higher for 36 km compared to 30-km trial at 80% and the 24-km trial at 10% and 40-100% of completion (P ≤ 0.02). We conclude that the increase in O2Hb and RPE during the 36-km trial, while a reduction in HR and PO is present, may indicate that the pre-frontal cortex may influence the regulation of exercise performance when deceived of the duration end-point by increasing perception of effort to reduce premature onset of physiological strain.


Enabling the next steps in cancer immunotherapy: from antibody-based bispecifics to multispecifics, with an evolving role for bioconjugation chemistry.
In the past two decades, immunotherapy has established itself as one of the leading strategies for cancer treatment, as illustrated by the exponentially growing number of related clinical trials. This trend was, in part, prompted by the clinical success of both immune checkpoint modulation and immune cell engagement, to restore and/or stimulate the patient's immune system's ability to fight the disease. These strategies were sustained by progress in bispecific antibody production. However, despite the decisive progress made in the treatment of cancer, toxicity and resistance are still observed in some cases. In this review, we initially provide an overview of the monoclonal and bispecific antibodies developed with the objective of restoring immune system functions to treat cancer (cancer immunotherapy), through immune checkpoint modulation, immune cell engagement or a combination of both. Their production, design strategy and impact on the clinical trial landscape are also addressed. In the second part, the concept of multispecific antibody formats, notably MuTICEMs (Multispecific Targeted Immune Cell Engagers & Modulators), as a possible answer to current immunotherapy limitations is investigated. We believe it could be the next step to take for cancer immunotherapy research and expose why bioconjugation chemistry might play a key role in these future developments.


A multidimensional model of legal cynicism.
Legal socialization researchers have been paying more attention to legal cynicism, but the manner in which the concept was operationalized varied greatly and measurement properties of existing scales did not always meet traditional thresholds. The objective of this study was to construct and test a multidimensional legal cynicism scale with strong psychometric properties. We conducted 2 independent studies. In Study 1, we used survey data from a university-based sample (N = 502) to estimate a promax-rotated exploratory factor model. In Study 2, we used survey data from a second university-based sample (N = 587) in a confirmatory factor model to replicate the findings from Study 1. Results from both studies indicated that legal cynicism possessed a 3-dimensional structure (i.e., legal antipathy, low legal legitimacy, and legal corruption) and was correlated with criminal offending. The new legal cynicism scale possessed strong psychometric properties and predictive validity. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


MyGeneFriends: A Social Network Linking Genes, Genetic Diseases, and Researchers.
The constant and massive increase of biological data offers unprecedented opportunities to decipher the function and evolution of genes and their roles in human diseases. However, the multiplicity of sources and flow of data mean that efficient access to useful information and knowledge production has become a major challenge. This challenge can be addressed by taking inspiration from Web 2.0 and particularly social networks, which are at the forefront of big data exploration and human-data interaction. MyGeneFriends is a Web platform inspired by social networks, devoted to genetic disease analysis, and organized around three types of proactive agents: genes, humans, and genetic diseases. The aim of this study was to improve exploration and exploitation of biological, postgenomic era big data. MyGeneFriends leverages conventions popularized by top social networks (Facebook, LinkedIn, etc), such as networks of friends, profile pages, friendship recommendations, affinity scores, news feeds, content recommendation, and data visualization. MyGeneFriends provides simple and intuitive interactions with data through evaluation and visualization of connections (friendships) between genes, humans, and diseases. The platform suggests new friends and publications and allows agents to follow the activity of their friends. It dynamically personalizes information depending on the user's specific interests and provides an efficient way to share information with collaborators. Furthermore, the user's behavior itself generates new information that constitutes an added value integrated in the network, which can be used to discover new connections between biological agents. We have developed MyGeneFriends, a Web platform leveraging conventions from popular social networks to redefine the relationship between humans and biological big data and improve human processing of biomedical data. MyGeneFriends is available at lbgi.fr/mygenefriends.


Examining patient benefit.
Healthcare policy, clinical practice and clinical research all declare patient benefit as their avowed aim. Yet, the conceptual question of what exactly constitutes patient benefit has received much less attention than the practical means of realising it. Currently, three key areas of conceptual unclarity make the achieved, real-world impact hard to quantify and disconnect it from the magnitude of the practical endeavour: (1) the distinction between objective and subjective benefit, (2) the relation between individual and population measures of benefit, and (3) the optimal measurement of benefit in research studies. A philosophical understanding of wellbeing is required to clarify these problems. Adopting a rigorous philosophical framework makes apparent that the differing goals of clinicians, researchers and research funders may make differing conceptions of patient benefit appropriate. A framework is proposed for developing rigour in methods for specifying and measuring patient benefit, and for matching benefit measures to different contexts.


[Aerobic bacterial flora from the digestive tract of the common vampire bat, Desmodus rotundus (Chiroptera: Phyllostomidae)].
This study addresses the composition of microbial flora in the vampire bat (Desmodus rotundus) primarily because all available data are outdated, and because of the economical significance of this bat species. Twenty-one bats were collected and their aerobic bacteria documented separately for stomach and intestine. Bacteria were identified through the Analytical Profile Index (API), and results analyzed with the APILAB software. A total of thirty bacterial species were isolated from sixteen females and five males. The most common species were Escherichia coli and Staphylococcus aureus, although other bacteria, such as Acinetobacterjohnsonii, Enterobacter sakazakii, Staphylococcus chromogenes, S. hyicus and S. xylosus were also common. The number of species found in the stomach and intestine was significantly different, and the intestine presented a higher diversity compared to the stomach. This has previously been found in other mammals and it is attributed to a reduction of acidity. Most of the species found in this study are considered normal components of the digestive tract of mammals, although other bacteria common in the skin of mammals and from aquatic environments were found. Bacteria from the skin may invade the vampire's stomach and/or intestine when the bat has contact with its prey, and may suggest that the vampire's feeding habit facilitates the invasion of other microbes not common in its digestive tract. The fact that bacteria from aquatic environments were also found suggests that D. rotundus, as previously found by other researchers, drinks free water when available, and water may be another source of microbial invasion.


Cigarette smoke extract induces oral squamous cell carcinoma cell invasion in a receptor for advanced glycation end-products-dependent manner.
Oral squamous cell carcinoma (OSCC) affects approximately 30,000 people and is associated with tobacco use. Little is known about the mechanistic effects of second-hand smoke in the development of OSSC. The receptor for advanced glycation end-products (RAGE) is a surface receptor that is upregulated by second-hand smoke and inhibited by semi-synthetic glycosaminoglycan ethers (SAGEs). Our objective was to determine the role of RAGE during cigarette smoke extract-induced cellular responses and to use SAGEs as a modulating factor of Ca9-22 OSCC cell invasion. Ca9-22 cells were cultured in the presence or absence of cigarette smoke extract and SAGEs. Cell invasion was determined and cells were lysed for western blot analysis. Ras and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) activation were determined. Treatment of cells with cigarette smoke extract resulted in: (i) increased invasion of OSCC; (ii) increased RAGE expression; (iii) inhibition of cigarette smoke extract-induced OSCC cell invasion by SAGEs; (iv) increased Ras, increased AKT and NF-κB activation, and downregulation by SAGEs; and (v) increased expression of matrix metalloproteinases (MMPs) 2, 9, and 14, and downregulation by SAGEs. We conclude that cigarette smoke extract increases invasion of OSCC cells in a RAGE-dependent manner. Inhibition of RAGE decreases the levels of its signaling molecules, which results in blocking the cigarette smoke extract-induced invasion.


Iconic Prosody in Story Reading.
Recent experiments have shown that people iconically modulate their prosody corresponding with the meaning of their utterance (e.g., Shintel et al., 2006). This article reports findings from a story reading task that expands the investigation of iconic prosody to abstract meanings in addition to concrete ones. Participants read stories that contrasted along concrete and abstract semantic dimensions of speed (e.g., a fast drive, slow career progress) and size (e.g., a small grasshopper, an important contract). Participants read fast stories at a faster rate than slow stories, and big stories with a lower pitch than small stories. The effect of speed was distributed across the stories, including portions that were identical across stories, whereas the size effect was localized to size-related words. Overall, these findings enrich the documentation of iconicity in spoken language and bear on our understanding of the relationship between gesture and speech.


Effect of two-dimensional confinement on switching of vertically aligned liquid crystals by an in-plane electric field.
We investigated the two-dimensional (2-D) confinement effect of liquid crystals (LCs) on the switching of vertically aligned LCs by an in-plane electric field. When an in-plane field is applied to a vertical alignment (VA) cell, virtual walls are built at the center of the interdigitated electrodes and at the middle of the gaps between them. The LC molecules are confined not only by the two substrates but also by the virtual walls so that the turn-off time of a VA cell driven by an in-plane field is dependent on the pitch of the interdigitated electrodes as well as the cell gap. Therefore, the turn-off time of a VA cell driven by an in-plane field can be reduced simply by decreasing the pitch of the interdigitated electrodes as a result of the enhanced anchoring provided by the virtual walls. The experimental results showed good agreement with a simple model based on the 2-D confinement effect of LCs.


Salvage of neglected unstable intertrochanteric fracture with cementless porous-coated hemiarthroplasty.
A cementless porous-coated femoral prosthesis with a long stem was implanted in seven patients who had untreated comminuted unstable intertrochanteric fractures of the femur associated with a posterior dislocation of the femoral head. The average age of the patients was 35 years (range, 25-52 years). The length of follow-up observation averaged 45 months (range, 23-60 months). The hip rating at the final follow-up examination ranged from 82 to 100 points (average, 96 points). The follow-up roentgenographs of these patients revealed complete consolidation of the fracture site and no evidence of subsidence or loosening of the prosthesis. There was no indication of detrimental bone remodeling phenomenon in this series. Hemiarthroplasty with a cementless, porous-coated, long-stem prosthesis can be effective treatment for this complex fracture dislocation.


Errors in interpreting the pretransfusion bedside compatibility test: an experimental study.
Analysis of reports of incidents, involving ABO incompatibility suggests that the main problem is poor interpretation of the pretransfusion bedside compatibility test (PBCT). We studied sources of error as experienced by nurses as to the blood groups of donor blood and of the recipient. According to their seniority in the profession and on the ward, 48 nurses were randomly selected from four transfusion sectors of the University Hospital of Grenoble, France. Each nurse interpreted 24 photos of PBCTs, including some with procedural irregularities, and was asked to assess the compatibility of the blood types of the donor and the recipient. At random, half the nurses were provided with a diagram to facilitate interpretation. The overall frequency of errors was 39.8%. Errors were fewer when the tests were interpreted as compatible (7.3%) or incompatible (6.3%), and when the nurse had been in the profession between 3 and 5 years and in the ward less than 3 years (25.5%), or worked in hematology (34.7%) or anesthesia (36.5%). Use of the diagram limited the number of errors, provided the test was interpretable (22.2%). PBCTs cannot be considered a valid safety procedure. We need other, more effective methods to reduce the risk of incompatibility accidents.


The identification of economically relevant health and social care services for mental disorders in the PECUNIA project.
Health economic research is still facing significant problems regarding the standardization and international comparability of health care services. As a result, comparative effectiveness studies and cost-effectiveness analyses are often not comparable. This study is part of the PECUNIA project, which aimed to improve the comparability of economic evaluations by developing instruments for the internationally standardized measurement and valuation of health care services for mental disorders. The aim of this study was to identify internationally relevant services in the health and social care sectors relevant for health economic studies for mental disorders. A systematic literature review on cost-of-illness studies and economic evaluations was conducted to identify relevant services, complemented by an additional grey literature search and a search of resource use measurement (RUM) questionnaires. A preliminary long-list of identified services was explored and reduced to a short-list by multiple consolidation rounds within the international research team and an external international expert survey in six European countries. After duplicate removal, the systematic search yielded 15,218 hits. From these 295 potential services could be identified. The grey literature search led to 368 and the RUM search to 36 additional potential services. The consolidation process resulted in a preliminary list of 186 health and social care services which underwent an external expert survey. A final consolidation step led to a basic list of 56 services grouped into residential care, daycare, outpatient care, information for care, accessibility to care, and self-help and voluntary care. The initial literature searches led to an extensive number of potential service items for health and social care. Many of these items turned out to be procedures, interventions or providing professionals rather than services and were removed from further analysis. The resulting list was used as a basis for typological coding, the development of RUM questionnaires and corresponding unit costs for international mental health economic studies in the PECUNIA project.


[Megaloblastic anemia: 30 cases in a district hospital].
The high incidence of megaloblastic anemia observed at our institution (2.1% of hospital admissions) prompted us to analyze the causes of cobalamin and/or folate deficiency in 30 patients admitted during the period 1983-1991 to the Medical Department of Locarno District Hospital. The study population includes 19 women and 11 men with a mean age of 69 years (range 28-91 years). All patients had severe macrocytic anemia (mean hemoglobin 74 +/- 23 g/l, MCV 121 +/- 12 fl), striking megaloblastic changes in aspirated marrow, and an elevated serum level of LDH (2170 +/- 2150 U/l). 19 patients had associated thrombocytopenia, 12 leukopenia and 11 both thrombocytopenia and leukopenia. Treatment led to prompt reticulocytosis and correction of megaloblastic changes in all patients, as well as to nearly complete resolution of the neurologic disorder in a patient with severe spastic ataxia. In 15 patients, megaloblastic anemia was caused by folate deficiency related to alcoholism (n = 6, mean age 55 years) and old age or poverty (n = 9, mean age 73 years). Cobalamin deficiency was present in 9 patients (mean age 69 years); it was due to pernicious anemia in 6 patients and to malabsorption in 2, while the cause remained unexplained in 1. The last patients (mean age 76 years) had deficiency of both cobalamin and folate, related to alcoholism (n = 3) or poverty (n = 3).


An "alternative finger" in robotic-assisted thoracic surgery: intraoperative ultrasound localization of pulmonary nodules.
Robotic-assisted thoracic surgery (RATS) has become a promising treatment for pulmonary neoplasms. During RATS, intraoperative ultrasonography can act as an "alternative finger" to "touch" and locate lesions, especially pulmonary nodules. This study was aimed to investigate the efficacy of intraoperative ultrasonographic localization during da Vinci RATS procedures. Patients with pulmonary nodules were randomly divided into an Experimental Group and Control Group in which nodules were respectively located using intraoperative ultrasonography or by the surgeon's anatomic knowledge. The success rates and relevant localization factors were compared between the groups and analyzed to conclude the efficacy of intraoperative ultrasonography. Additionally, the intraoperative ultrasonography learning curve was analyzed to evaluate each surgeon's ability to independently perform intraoperative ultrasonography. Thirty-four patients were included in the study (n = 17/group). Respectively, the Experimental Group and Control Group comprised 41.2% and 58.9% women (p= 0.937), and had average ages of 55.5 and 55.8 years. In the Experimental group, ultrasonographic localization for mixed ground-glass nodules with CT values of -500 to -100 Hounsfield units had an efficacy of 87.5%. By contrast, the localization efficacy in Control Group was 20.0% (p=0.032).A single surgeon without prior experience performed intraoperative ultrasonography in 20 cases, and the latter 10 procedures required significantly less time relative to the former 10 procedures (p=0.000). During RATS, the use of intraoperative ultrasonography as an "alternative finger" to "touch" and findthe accurate location of pulmonary nodules, especially mixed ground-glass nodules, is warranted.


Quantifying disease progression in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic.


Structural basis of heme reactivity in myoglobin and leghemoglobin: thermal difference spectra.
Thermal pertubation difference spectra of sperm whale myoglobin (Mb) and soybean leghemoglobin a (Lb a) in the near-ultraviolet reveal similarities in the tryptophan environment of the two proteins. Of the two tryptophans in each protein, one has its indolyl NH group fully exposed to aqueous solvent, while the other behaves as if it were surrounded by motile but nonpolar residues with little access to water. These environments are not significantly altered by removal of the heme group. Assuming conformational homology, the helix-spacing role of Trp-A12 in Mb (Kendrew, J.C. (1962), Brookhaven Symp. Biol. 15, 216-228) may be taken over, in Lb a, by Trp-H8 which, though remote in linear sequence, would occupy a suitable spatial location. Thermal difference spectra in the Soret and visible regions of pure high-spin (fluoroferric) and pure low-spin (cyanoferric) complexes showed a red shift on cooling Mb complexes, reflecting a predominantly nonpolar environment around the heme, but a blue shift on cooling Lb complexes, reflecting a more solvent-exposed environment. Thermal difference spectra using rose bengal as a probe of the heme pockets in the two apoproteins supported these conclusions. Thermal difference spectra for the high-spin complexes of both Mb and Lb are slightly larger in magnitude than in the low-spin complexes. This may reflect a more flexible heme pocket in the high-spin state, as suggested by recent circular dichroic results. A structural basis for the high oxygen affinity of Lb compared with Mb is proposed, based upon the observed differences in polarity and flexibility of the heme pocket and in amino acid substitutions.


IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes.
We have generated transgenic nonobese diabetic (NOD) mice expressing dominant negative mutant IFN-gamma receptors on pancreatic beta cells to investigate whether the direct effects of IFN-gamma on beta cells contribute to autoimmune diabetes. We have also quantitated by flow cytometry the rise in class I MHC on beta cells of NOD mice with increasing age and degree of islet inflammatory infiltrate. Class I MHC expression increases gradually with age in wild-type NOD mice; however, no such increase is observed in the transgenic beta cells. The transgenic mice develop diabetes at a similar rate to that of wild-type animals. This study dissociates class I MHC upregulation from progression to diabetes, shows that the rise in class I MHC is due to local IFN-gamma action, and eliminates beta cells as the targets of IFN-gamma in autoimmune diabetes.


[Development of a questionnaire for measuring effort-reward imbalance in household and family work].
Siegrists concept of effort-reward imbalance (ERI) had been shown to be associated with a broad range of health impairments, in particular cardiovascular diseases and depression. The original questionnaire was designed to assess ERI in the field of occupational work. This paper reports on a newly developed questionnaire for the assessment of ERI in household and family work. Analogous to the original version, it is divided into two components: (i) dysbalance of effort and reward (extrinsic component), and (ii) over-commitment (intrinsic components). The questionnaire was tested with data drawn from a clinical sample of mothers (n = 567) in rehabilitation clinics. Factor analyses have reproduced the two main dimensions "effort" and "reward". Relevant aspects of reward at home were (i) meaningfulness, (ii) social gratification, (iii) appreciation from the spouse, and (iv) affection for the child. Finally a 19-item questionnaire for assessing ERI in household and family work (ERI-M) and a four-item measure for measuring parental over-commitment (Over-M) are available. The psychometric properties of both instruments are good to satisfactory.


Effects of toothbrushing on eroded dentine.
It is an established assumption that eroded dental hard tissues are particularly prone to toothbrush abrasion. Only a few studies have aimed to show this for dentine and, if so, disregarded the complex histological structure of this tissue. Therefore, the present study sought (i) to investigate the effects of toothbrushing on eroded dentine and (ii) to analyze how the organic matrix influences the outcome of established methods for quantifying dental hard tissue loss. The effects of brushing were investigated by optical (P-O) and mechanical (P-M) profilometry, by longitudinal microradiography (LMR), and by scanning electron microscopy (SEM). The SEM images showed that a demineralized organic layer had developed, which was unaffected by brushing. For substance loss, there was no significant difference between eroded and eroded/abraded samples. Considerable differences occurred, however, when results from the different methods were compared. P-O yielded the lowest (7.0 +/- 3.4 microm) and LMR the highest (109.8 +/- 10.7 microm) substance loss values. When the organic material was removed enzymatically, all methods gave comparable results. The results of this study do not lend support to the notion that brushing increases substance loss of eroded dentine. Profilometry was not suitable for measuring mineral loss, unless the organic material was removed.


An unusual presentation of filariasis: a case report.
Filariasis and its consequences are a major health problem in tropical countries, including the Indian subcontinent. Despite its high incidence, it is unusual to find microfilaria in fine needle aspiration cytology (FNAC) smears. We present a case of subcutaneous firm to cystic swelling, aspiration of which revealed a large number of microfilaria. A 30-year-old man presented with a chain of intermittent, firm swellings in both arms. FNAC of the swellings revealed a large number of 4 microfilariae with associated giant cell reaction and inflammatory cell-like eosinophils. Besides the documented usual mode of presentation of filarial infection, it can present in an atypical manner, so careful examination of aspirates from the subcutaneous swellings, especially in filariasis endemic zones, is very important.


Production of the effector cytokine interleukin-17, rather than interferon-γ, is more strongly associated with autoimmune hemolytic anemia.
Interleukin-17A is the signature cytokine of the Th17 subset and drives inflammatory pathology, but its relevance to autoantibody-mediated diseases is unclear. Th1 cells secreting interferon-γ have been implicated in autoimmune hemolytic anemia, so the aim was to determine which cytokine is more closely associated with disease severity. Interferon-γ and interleukin-17A were measured in the sera of patients with autoimmune hemolytic anemia and healthy donors, and in peripheral blood mononuclear cell cultures stimulated with autologous red blood cells, or a panel of peptides spanning red blood cell autoantigen. Serum interleukin-17A, but not interferon-γ, was significantly raised in patients with autoimmune hemolytic anemia (P<0.001), and correlated with the degree of anemia. Interleukin-17A was also more prominent in the responses of peripheral blood mononuclear cells from patients with autoimmune hemolytic anemia to red blood cells, and, again unlike interferon-γ, significantly associated with more severe anemia (P<0.005). There were no interleukin-17A responses to red blood cells by peripheral blood mononuclear cells from healthy donors. Specific autoantigenic peptides were identified that elicit patients' interleukin-17A responses. Interleukin-17A makes a previously unrecognized contribution to the autoimmune response in autoimmune hemolytic anemia, challenging the model that the disease is driven primarily by Th1 cells. This raises the possibility that Th17, rather than Th1, cells should be the target for therapy.


Expiratory chest radiographs do not improve visibility of small apical pneumothoraces by enhanced contrast.
Demonstration of small apical pneumothoraces is supposed to be facilitated by expiratory chest radiographs. This study aimed to analyse the assumed enhancement of visual contrast on expiratory chest radiographs in patients with small apical pneumothoraces. Optical densities (OD) were obtained with a densitometer (X-rite 3001) on 54 paired inspiratory and expiratory chest radiographs of 22 consecutive patients with small apical pneumothoraces. The ODs were measured: at the intervertebral space between the first and second thoracic vertebrae (Area 1); at the peripheral part of the affected lung parenchyma (Area 2); and at the adjacent intrapleural space (Area 3). Excellent correlations of OD of each area were obtained between paired inspiratory and expiratory chest radiographs. The ODs of all areas on expiratory chest radiographs were significantly higher than on inspiratory chest radiographs. Contrast between pulmonary parenchyma and intrapleural air in inspiratory and expiratory films did not differ significantly. Expiratory chest radiographs do not improve visibility of small apical pneumothoraces by enhanced contrast between pulmonary parenchyma and intrapleural air. Expiratory chest radiographs show equally increased OD in the area of lung tissue and intrapleural air, caused by increased extrapulmonary tissue density during expiration, resulting in increased radiation exposure monitored by the ionization chambers of standard radiological equipment. If expiratory chest radiographs are really improving the visibility of apical pneumothoraces, there must be other reasons than contrast enhancement to explain this.


Actions as space-time shapes.
Human action in video sequences can be seen as silhouettes of a moving torso and protruding limbs undergoing articulated motion. We regard human actions as three-dimensional shapes induced by the silhouettes in the space-time volume. We adopt a recent approach for analyzing 2D shapes and generalize it to deal with volumetric space-time action shapes. Our method utilizes properties of the solution to the Poisson equation to extract space-time features such as local space-time saliency, action dynamics, shape structure and orientation. We show that these features are useful for action recognition, detection and clustering. The method is fast, does not require video alignment and is applicable in (but not limited to) many scenarios where the background is known. Moreover, we demonstrate the robustness of our method to partial occlusions, non-rigid deformations, significant changes in scale and viewpoint, high irregularities in the performance of an action, and low quality video.


Heritability of high reading ability and its interaction with parental education.
Moderation of the level of genetic influence on children's high reading ability by environmental influences associated with parental education was explored in two independent samples of identical and fraternal twins from the United States and Great Britain. For both samples, the heritability of high reading performance increased significantly with lower levels of parental education. Thus, resilience (high reading ability despite lower environmental support) is more strongly influenced by genotype than is high reading ability with higher environmental support. This result provides a coherent account when considered alongside results of previous research showing that heritability for low reading ability decreased with lower levels of parental education.


Development of antimicrobial gelatin films with boron derivatives.
Food packaging technology has been advancing to provide safe and high quality food products and to minimize food waste. Moreover, there is a dire need to replace plastic materials in order to reduce environmental pollution. The aim of this study was to prepare biodegradable antimicrobial packaging films from gelatin. Boric acid, disodium octaborate tetrahydrate, and sodium pentaborate were incorporated as the antimicrobial agents. Films containing boric acid and its salts showed antibacterial effect against Staphylococcus aureus and Pseudomonas aeruginosa, as well as antifungal and anticandidal effects against Aspergillus niger and Candida albicans. The mechanical strength of the films was mostly enhanced by the addition of boron derivatives. The rheological measurements and Fourier-transform infrared spectroscopy results suggest that boron derivatives did not interfere with the network formation during gelling. The morphology of boron-added antimicrobial films was found to be similar to the morphology of the control . In conclusion, the newly developed gelatin films containing 10% or 15% disodium octaborate (g/g gelatin) might be good candidates for biodegradable antimicrobial packaging materials.


Identification of systemic responses in soybean nodulation by xylem sap feeding and complete transcriptome sequencing reveal a novel component of the autoregulation pathway.
Establishment of the nitrogen-fixing nodulation symbiosis between legumes and rhizobia requires plant-wide reprogramming to allow infection and development of nodules. Nodulation is regulated principally via a mechanism called autoregulation of nodulation (AON). AON is dependent on shoot and root factors and is maintained by the nodulation autoregulation receptor kinase (NARK) in soybean. We developed a bioassay to detect root-derived signalling molecules in xylem sap of soybean plants which may function in AON. The bioassay involves feeding of xylem extracts via the cut hypocotyl of soybean seedlings and monitoring of molecular markers of AON in the leaf. Transcript abundance changes occurring in the leaf in response to feeding were used to determine the biological activity of the extracts. To identify transcript abundance changes that occur during AON, which may also be used in the bioassay, we used an RNA-seq-based transcriptomics approach. We identified changes in the leaves of bioassay plants fed with xylem extracts derived from either Bradyrhizobium japonicum-inoculated or uninoculated plants. Differential expression responses were detected for genes involved in jasmonic acid metabolism, pathogenesis and receptor kinase signalling. We identified an inoculation- and NARK-dependent candidate gene (GmUFD1a) that responds in both the bioassay and intact, inoculated plants. GmUFD1a is a component of the ubiquitin-dependent protein degradation pathway and provides new insight into the molecular responses occurring during AON. It may now also be used in our feeding bioassay as a molecular marker to assist in identifying the factors contributing to the systemic regulation of nodulation.


Defining an Optimal Cut-Point Value in ROC Analysis: An Alternative Approach.
ROC curve analysis is often applied to measure the diagnostic accuracy of a biomarker. The analysis results in two gains: diagnostic accuracy of the biomarker and the optimal cut-point value. There are many methods proposed in the literature to obtain the optimal cut-point value. In this study, a new approach, alternative to these methods, is proposed. The proposed approach is based on the value of the area under the ROC curve. This method defines the optimal cut-point value as the value whose sensitivity and specificity are the closest to the value of the area under the ROC curve and the absolute value of the difference between the sensitivity and specificity values is minimum. This approach is very practical. In this study, the results of the proposed method are compared with those of the standard approaches, by using simulated data with different distribution and homogeneity conditions as well as a real data. According to the simulation results, the use of the proposed method is advised for finding the true cut-point.


Dynamic sustained attention markers differentiate atypical development: The case of Williams syndrome and Down's syndrome.
Impaired sustained attention is considered an important factor in determining poor functional outcomes across multiple cognitive and behavioural disorders. Sustained attention is compromised for both children with Williams syndrome (WS) and Down's syndrome (DS), but specific difficulties remain poorly understood because of limitations in how sustained attention has been assessed thus far. In the current study, we compared the performance of typically developing children (N = 99), children with WS (N = 25), and children with DS (N = 18), on a Continuous Performance Task - a standard tool for measuring sustained attention. In contrast to previous studies, primarily focused on overall differences in mean performance, we estimated the extent to which performance changed over time on task, thus focusing directly on the sustained element of performance. Children with WS and children with DS performed more poorly overall compared to typically developing children. Importantly, measures specific to changes over time differentiated between children with the two syndromes. Children with WS showed a decrement in performance, whereas children with Down's syndrome demonstrated non-specific poor performance. In addition, our measure of change in performance predicted teacher-rated attention deficits symptoms across the full sample. An approach that captures dynamic changes in performance over assessments may be fruitful for investigating similarities and differences in sustained attention for other atypically developing populations.


Absorption of phosphate in the jejunum of patients with chronic renal failure before and after correction of vitamin D deficiency.
To examine the role of vitamin D in human phosphate absorption, we studied patients with chronic renal disease on hemodialysis, before and after correction of vitamin D deficiency. Thirty-centimeter segments of jejunum were perfused with test solutions containing varying concentrations of phosphate; phosphate absorption rate and electrical potential difference were measured. The data reveal that dialysis patients have depressed phosphate absorption, but the degree of this depression is modest, compared to the extent of their depressed calcium absorption. Therapy with 1,25-(OH)2D3 for 1 wk restored phosphate absorption rate to near normal. With or without 1,25-(OH)2D3 therapy, phosphate absorption was not influenced by calcium in the perfused test solutions. Examination of kinetic data suggests that the vitamin D deficiency of chronic renal failure causes a reduction by half in the rate of active phosphate absorption. By contrast, our data suggest that vitamin D deficiency does not alter passive phosphate absorption. By aspirating jejunal contents after ingestion of different foods, with and without aluminum hydroxide, the physiologic luminal phosphate concentration was found to vary between 0.7 and 12.2 mM. At the lower end of this range, phosphate absorption would be mediated entirely by active transport; at the higher phosphate concentrations, phosphate absorption would be mainly mediated by passive transport.


Magnetic field controlled charge density wave coupling in underdoped YBa2Cu3O6+x.
The application of magnetic fields to layered cuprates suppresses their high-temperature superconducting behaviour and reveals competing ground states. In widely studied underdoped YBa2Cu3O6+x (YBCO), the microscopic nature of field-induced electronic and structural changes at low temperatures remains unclear. Here we report an X-ray study of the high-field charge density wave (CDW) in YBCO. For hole dopings ∼0.123, we find that a field (B∼10 T) induces additional CDW correlations along the CuO chain (b-direction) only, leading to a three-dimensional (3D) ordered state along this direction at B∼15 T. The CDW signal along the a-direction is also enhanced by field, but does not develop an additional pattern of correlations. Magnetic field modifies the coupling between the CuO2 bilayers in the YBCO structure, and causes the sudden appearance of the 3D CDW order. The mirror symmetry of individual bilayers is broken by the CDW at low and high fields, allowing Fermi surface reconstruction, as recently suggested.


Antiaggressive activity of hyperforin: A preclinical study.
The aim of present study was to investigate the in vivo antiaggressive activity of hyperforin using defensive and offensive behavioral models in rodents. Adult male rats and mice were used for the present study. Animals were divided into three groups, with 6 animals in each. Lorazepam was used as standard antiaggressive agent. Animals were treated once daily, for seven consecutive days. Hyperforin (10 mg/kg, i.p.) was injected in a volume of 10 mL/kg for seven consecutive days. Standard group was treated with lorazepam (2.5 mg/kg, i.p.). The control group was treated with equal volume of vehicle (0.3% carboxy methyl cellulose suspension, i.p.). Animals were screened for aggressive behavior before dividing them into groups. At the end of 7 days, experiments were performed. Antiaggressive activity was evaluated using following validated models of aggression viz. foot shock-induced aggression, isolation-induced aggression, resident-intruder aggression and water competition test. Hyperforin treatment significantly (p < 0.001) reduced various aggressive parameters viz. latency to first attack and number of fights in isolation induced aggression, resident intruder aggression and foot shock induced aggression tests. In water competition test, hyperforin treatment significantly (p < 0.001) reduced the duration of water consumption and frequency of water spout possession. We conclude that hyperforin, the major lipophilic compound contained in extracts of Hypericum perforatum, is thus responsible for the antiaggressive activity, suggesting the therapeutic potential of hyperforin as an antiaggressive agent.


Effectiveness of Adenotonsillectomy and Risk of Velopharyngeal Insufficiency in Children With Prader-Willi Syndrome.
(1) Review effectiveness of adenotonsillectomy (T&A) for obstructive sleep apnea (OSA) in children with Prader-Willi syndrome (PW). (2) Examine the incidence of velopharyngeal insufficiency (VPI) after T&A in this population. (3) Compare outcomes of T&A in PW and Trisomy 21 (T21) patients. Outcomes after T&A in a PW cohort were retrospectively reviewed and compared to those in patients with T21. The study cohort included 22 PW patients. They were compared to 47 T21 patients who also underwent T&A. Eighteen percent (N = 4) of the PW patients had postoperative VPI requiring a corrective procedure, while there were no patients within the T21 cohort who had identified VPI ( P < .05). In those patients that had a postoperative polysomnogram, the mean decrease in obstructive apnea-hypopnea index (OAHI) of the PW and T21 patients measured 8.4 and 4.7 points, respectively ( P = .3). This study demonstrated a higher rate of VPI after T&A in PW children as compared to another at-risk cohort, T21 patients. While the OAHI decreased after T&A in both groups, a significant number of children with PW or T21 had persistent OSA. Further investigation into the optimal management of OSA, while preventing treatment complications such as VPI, is needed for children with these high-risk conditions.


Fresh frozen plasma increases adhesion molecule expression on human pulmonary endothelial cells.
Current blood banking practices allow fresh frozen plasma (FFP) to be thawed and then stored for 5 d between 1 and 6 °C. We hypothesized that aged plasma (d 5 FFP) would be pro-inflammatory to the endothelium compared with fresh plasma (d 0 FFP). Human pulmonary endothelial cells (PECs) were treated with (1) media, (2) media + lipopolysaccharide (LPS), (3) lactated Ringer's (LR), (4) LR + LPS, (5) d 0 FFP, (6) d 0 FFP + LPS, (7) d 5 FFP, and (8) d 5 FFP + LPS. After a 24 h incubation, the PECs were stained with antibodies for I-CAM, V-CAM, P-selectin, and E-selectin. The cells were subsequently analyzed by flow cytometry. In both PEC groups treated with FFP and stimulated with LPS, I-CAM, V-CAM, P-selectin, and E-selectin were significantly up-regulated compared with LR when stimulated by LPS. FFP at both ages significantly increased expression of four different adhesion molecules compared with LR in PECs. This may represent a possible mechanism for increased leukocyte binding on the endothelium as a result of FFP transfusion.


Potassium map from Chang'E-2 constraints the impact of Crisium and Orientale basin on the Moon.
KREEP materials were thought to be last crystallized at the lunar crust and mantle boundary. Impact cratering and volcanism are mainly responsible for their distributions on the lunar surface. Therefore, observation of global KREEP materials and investigation of distributions in the areas of large basins are of critical importance to understand the geologic history of the Moon. Here we report the new global potassium distribution on the Moon detected by Chang'E-2 Gamma-ray Spectrometer. We found that our new measurements are in general agreement with previous observation. A new finding and an important difference is that relatively higher K abundances in the Mare Crisium and Mare Orientale than their surrounding rims were detected for the first time. In light of our observations in these two areas, we propose that Crisium and Orientale basin-forming impact events may have penetrated to the lower crust and excavate the deeper materials to the lunar surface.


Regional bond strengths of self-etching/self-priming adhesive systems.
The purpose of this study was to measure the regional tensile bond strengths (TBS) at various portions of human tooth enamel and dentin, and to observe the resin-dentin interfaces of two commercially available self-etching/self-priming adhesive systems by scanning electron microscopy (SEM). Twelve extracted human cuspid teeth were used to measure TBS and four additional teeth were used for scanning electron microscopy (SEM). Outer enamel and dentin were removed from the labial tooth surfaces to form a long cavity preparation into middle dentin extending from the mid-crown to the apex of the root within the same tooth. Either Clearfil Liner Bond 2 (LB 2, Kuraray) or Fluoro Bond (FB, Shofu) was bonded to the surfaces, and covered with resin-composite. The resin-bonded teeth were serially sliced at right angles to the long axis of the tooth, and the bonded surfaces were trimmed to give a bonded cross-sectional surface area of 1 mm2 for TBS tests. LB 2 and FB showed significantly higher TBS in coronal, cervical and middle root dentin than that in enamel and apical root dentin. SEM showed that the thickness of the hybrid layer of both systems was about 1.0 microm in coronal, cervical and middle root dentin, and less than 0.5 microm in apical root dentin. These results suggested that the self-etching/self-priming systems produce good adhesion in coronal, cervical and middle root dentin by creating thin hybrid and transitional layers, but bonding to enamel and apical root dentin should be improved.


Arthroscopic technique for the knee in morbidly obese patients.
Patients with morbid obesity present an additional surgical difficulty for routine knee arthroscopy. Accurate portal placement in these patients is of utmost importance in order to achieve adequate access to the surgical pathology. To facilitate portal placement, we changed our standard surgical technique, establishing operative portals under direct arthroscopic visualization. We present our technique in this article as an option in the approach to treating these patients.


Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: results of a matched cohort study.
Prospective randomized and retrospective studies on adjunctive chemotherapy in patients with advanced locoregional nasopharyngeal carcinoma have yielded conflicting results and the role of chemotherapy in this disease had not been clearly defined. The authors report the results of a single institution, matched cohort study comparing a group of 61 patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy followed by radiation therapy with a matched group treated with radiotherapy alone. Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy (cisplatin, 100 mg/m2 on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m2, on Days 1-5) for 3 cycles followed by definitive radiation therapy (CT/RT group). This group was matched with a group of 61 patients from a population of 378 patients who received radiation therapy alone (RT group). Matching characteristics were T classification, N classification, histology, and level of cervical lymph node metastases. These characteristics were found to be significant determinants of distant metastasis (DM) and/or survival in a multivariate analysis that was performed in the entire radiotherapy group. Radiation therapy consisted of 66-72 gray in 6.5 to 7 weeks in both groups. Fifty-nine patients (97%) in both groups had Stage IV disease. Fifteen patients (25%) in both groups had lower cervical lymph node metastases. The tumor histologic types also had similar distribution in both groups. Median follow-up time among surviving patients of the CT/RT group was 4.9 years (range, 1.3-9.8 years). The 5-year cumulative incidence of DM was 19 +/- 5% for the CT/RT group and 34 +/- 6% for the RT alone group (P = 0.019; log rank test). This reduction in distant failure was more prominent in patients with intermediate (N2-N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 disease; lower cervical lymph nodes) of DM. This reduction in DM translated into improvement in disease free survival (DFS) and overall survival (OS). The 5-year actuarial DFS rates were 64 +/- 6% for the CT/RT group compared with 42 +/- 7% for the RT group (P = 0.015). The 5-year actuarial OS rates were 69 +/- 6% (CT/RT group) and 48 +/- 7% (RT group), respectively (P = 0.012). The incidence of locoregional failure was slightly lower in the CT/RT group, but this difference did not reach statistical significance. There was no significant difference in the incidence and severity of acute mucositis between the two groups during radiotherapy. The 5-year cumulative incidence of Grade 3 or higher late complications was also similar in both groups (5 +/- 3% in the CT/RT group and 8 +/- 3% in the RT group; P = 0.721). This matched cohort study provides additional evidence that induction cisplatin-5-FU chemotherapy prior to definitive radiation improves freedom from distant metastasis, DFS, and OS for patients with locoregional Stage IV nasopharyngeal carcinoma without increasing treatment-related morbidity.


Sequence variation of the human immunodeficiency virus primer-binding site suggests the use of an alternative tRNA(Lys) molecule in reverse transcription.
Retroviruses use a cellular tRNA molecule as primer for reverse transcription. The complementarity between the 3' end of this tRNA and a sequence near the 5' end of the viral RNA, the primer-binding site (PBS), allows the primer to anneal onto the viral RNA. During reverse transcription 18 nucleotides of the tRNA primer are copied into the viral cDNA, thereby regenerating the PBS sequence of the progeny. Thus, the PBS sequence reveals which primer was used. Human immunodeficiency viruses are known to replicate efficiently with tRNA(Lys3) as primer. Examination of the PBS sequence in natural and laboratory isolates indicates that a variant tRNA(Lys) is occasionally used as primer. This variant, for which the murine genomic sequence was described previously, was termed tRNA(Lys5) and differs from tRNA(Lys3) at five nucleotide positions. These results suggest that HIV uses both tRNA(Lys3) and tRNA(Lys5) molecules as primer, causing a switch of the PBS sequence.


Neighborhoods, Work, and Health: Forging New Paths Between Social Determinism and Well-Being.
Tribalism in America and our polarized body politic has, sadly, become part of our daily digest. Is it possible that place-based discrimination will be shown to be an even more powerful impediment to our collective well-being than other formidable health influencers like race or income? If so, how would such a social diagnosis inform strategic planning in health promotion? Waddell and Reed wrote about "possible causal pathways" that show the interaction effects, both positive and negative, between work, health, and well-being. That businesses have focused on individual choices, rather than social influences, is not merely a philosophical leaning of the private sector. Individualism has dominated collectivism in the health care, health research, and health promotion sectors as well. Of the $36 billion approved this year to fund the National Institutes of Health, most will go to biomedical research and a paltry $11 million will be allocated to worksite health promotion. Similarly, in spite of the training of public health professionals about the primacy of social determinants as a predictor of well-being, health education and behavior research over the past 2 decades has overwhelmingly focused on individual interventions and interpersonal characteristics. A new federal survey of worksite health promotion in America shows modest growth in the past decade in the number of companies sponsoring comprehensive approaches to worksite health promotion. However, of the 5 elements constituting a comprehensive approach, the greatest gain in the past two decades has been the increase in companies offering a supportive social and physical environment. This editorial argues that we must think more deliberately about the causal chain that links neighborly social support and collective well-being if we are ever to solve for related issues like obesity, mental illness, and addiction.


[Pharmacological treatment of borderline personality disorders. Several options for symptom reduction but nothing for the disorder per se].
There are few guidelines for pharmacological treatment of personality disorders. Some possible explanations for this is discussed: methodological problems, comorbidity and treatment traditions. The few controlled studies published are marred by methodological difficulties such as high frequency of drop outs, lack of compliance, short period of follow-up and differences in diagnostic procedures. The authors propose a dimensional approach focusing on cognitive, affective, anxiety and impulse dysfunction when selecting suitable pharmacological treatment. Global improvement can be seen, when target symptoms are successfully treated. Pharmacological treatment can not replace other treatment strategies such as psychosocial programs. The authors also discuss how pharmacological treatment can be understood in a psychological context. Non-selective MAO-inhibitors are probably underused in Sweden.


[The best intervention for depression is early detection and prevention in youth].
Background A more preventive and proactive approach in youth mental health care can contribute to reduce the severity of psychological problems in young people and help to reduce the risk on treatment resistance. Aim To show opportunities to organize youth mental health care more proactively. Method Discuss new approaches based on existing literature and examples from clinical practice. Results It is essential that young people receive treatment that is appropriate for the severity of their problems. Early detection and prevention can be systematically carried out in collaboration with public health service and schools. In addition, it is imperative that young people receive appropriate (specialized) mental health care based on their prognosis. Conclusion Committing to the right care at the right time is essential to prevent the development of co-morbidities, stagnation in development tasks and therapy resistance. Tijdschrift voor psychiatrie 63(2021)2, 111-114.


Ocular Manifestations of Flavivirus Infections.
Flaviviruses are a group of positive-sense, single-stranded RNA viruses predominantly transmitted by arthropods (mainly mosquitoes) that cause severe endemic infections and epidemics on a global scale. They represent a major cause of systemic morbidity and death and are expanding worldwide. Among this group, dengue fever, the West Nile virus, yellow fever, Japanese Encephalitis, and, recently, the Zika virus have been linked to a spectrum of ocular manifestations. These manifestations encompass subconjunctival hemorrhages and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatments of flavivirus infections are currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for the yellow fever virus, dengue virus, and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic manifestations of the foremost flavivirus-associated human diseases.


Circular dichroism in K-shell ionization from fixed-in-space CO and N2 molecules.
We have measured the angular distributions of 1s photoelectrons excited by circularly and linearly polarized light from fixed-in-space CO and N2 molecules, in the vicinity of their shape resonances. A strong circular dichroism, i.e., a strong dependence on the sense of rotation of the polarization vector of the photons, is found for both molecules. State-of-the-art one-electron multiple scattering and partially correlated random phase approximation calculations are in good agreement with many, but not all, aspects of the experimental data.


Interprofessional practice and education: holistic approaches to complex health care challenges.
The incidence of chronic health conditions continues to rise worldwide. As a result, many groups and decision makers are calling for greater use of interprofessional health care teams and education to effectively address the social, psychological, biological, environmental, and economic dimensions inherent in these health care challenges. This article examines interprofessional practice (IPP) and interprofessional education (IPE) and addresses the following questions: (1) What is IPP; (2) What is IPE; (3) What competencies are necessary to effectively engage in IPP; (4) Who should be educated to serve on IPP health delivery teams; and (5) What educational model can best prepare health care professionals with the skills and practice experiences needed to address complex health issues in a comprehensive fashion? We propose a unique university-based IPE model that effectively addresses complex health issues and maximizes collaboration among clinical, nonclinical, and community stakeholders.


Effect of Arthroscopic Stabilization on In Vivo Glenohumeral Joint Motion and Clinical Outcomes in Patients With Anterior Instability.
Glenohumeral joint (GHJ) dislocations are common, and the resulting shoulder instability is often treated with arthroscopic stabilization. These procedures result in favorable clinical outcomes, but abnormal GHJ motion may persist, which may place patients at risk for developing osteoarthritis. However, the effects of shoulder instability and arthroscopic stabilization on GHJ motion are not well understood. GHJ motion is significantly influenced by anterior instability and arthroscopic stabilization, but postsurgical measures of GHJ motion are not different from those of control subjects. Controlled laboratory study. In vivo GHJ motion was measured by applying a computed tomographic model-based tracking technique to biplane radiographic images acquired during an apprehension test in healthy control subjects (n = 11) and anterior instability patients (n = 11). Patients were tested before surgery and at 6 months after surgery. Control subjects were tested once. Shoulder strength, active range of motion (ROM), and the Western Ontario Shoulder Instability (WOSI) index were also measured. Before surgery, the humerus of the instability patients during the apprehension test was located significantly more anteriorly on the glenoid (7.9% of glenoid width; 2.1 mm) compared with that of the controls (P = .03), but arthroscopic stabilization moved this joint contact location posteriorly on the glenoid (4.7% of glenoid width; 1.1 mm; P = .03). After surgery, GHJ excursion during the apprehension test was significantly lower (14.7% of glenoid width; 3.6 mm) compared with presurgical values (19.4% of glenoid width; 4.7 mm; P = .01) and with that of the controls (22.4% of glenoid width; 5.7 mm; P = .01). The external and internal rotation strength of patients was significantly lower than that of the controls before surgery (P < .05), but differences in strength did not persist after surgery (P > .17). External rotation ROM in patients was significantly lower than that in control subjects both before and after arthroscopic stabilization (P < .01). The WOSI score improved significantly, from 48.3 ± 13.1 presurgery to 86.3 ± 16.5 after surgery (P = .0002). In patients with anterior instability, arthroscopic stabilization significantly improves measures of strength, ROM, and clinical outcome. However, GHJ excursion is not fully restored to levels seen in the control subjects. Although arthroscopic stabilization satisfactorily restores most clinical outcome measures, GHJ excursion and external rotation ROM remain compromised compared with healthy control subjects and may contribute to the development of osteoarthritis in patients with anterior instability.


Comparative evaluation of Ambu Aura-i and Fastrach™ intubating laryngeal mask airway for tracheal intubation: A randomized controlled trial.
Ambu Aura-i was compared with Fastrach™ (FT)-laryngeal mask airway (LMA) as a conduit for tracheal intubation. A hundred consenting patients were randomly allocated into two groups of 50 patients each in a prospective randomized study. Standard anesthesia technique was used for all patients and FT-LMA or Ambu Aura-i was selected. After insertion of airway device, the cuff was inflated and ventilation was attempted. Once satisfactory ventilation was achieved, with or without maneuvers, a fiberoptic scoring for glottis view was noted. A polyvinylchloride (PVC) tracheal tube of appropriate size was inserted through the airway device as per procedure. If no resistance was felt while advancing the tracheal tube, it was fully inserted into the device and tracheal tube cuff was inflated. The device was removed and tracheal tube was left in situ. If the first attempt failed during tracheal tube insertion, the recommended maneuvers were used. A maximum of three attempts were allowed for intubation. First attempt for tracheal intubation attempt was a blind, second attempt was made with maneuver. If second attempt of intubation was unsuccessful, fiberoptic-guided intubation was performed as a third attempt. When tracheal intubation was unsuccessful, it was performed by direct laryngoscopy and considered as failed intubation. Rest of the anesthesia management was as per the discretion of attending anesthesiologists. The success rate of device insertion, fiberoptic score of glottis view, tracheal intubation via FT-LMA or Aura-i and time were recorded. Both FT-LMA and Aura-i were successfully placed within two attempts. The success rate of blind intubation was 92% in FT-LMA and 76% in Aura-i (P < 0.01). Time taken for tracheal intubation at first attempt was lesser in group FT-LMA and Aura-i, respectively (P < 0.01). Fiberoptic-guided intubation success rate was higher with Aura-i than with FT-LMA. FT-LMA had a higher success rate in facilitating blind tracheal intubation compared with Ambu Aura-i.


Synthesizing Images From Spatio-Temporal Representations Using Spike-Based Backpropagation.
Spiking neural networks (SNNs) offer a promising alternative to current artificial neural networks to enable low-power event-driven neuromorphic hardware. Spike-based neuromorphic applications require processing and extracting meaningful information from spatio-temporal data, represented as series of spike trains over time. In this paper, we propose a method to synthesize images from multiple modalities in a spike-based environment. We use spiking auto-encoders to convert image and audio inputs into compact spatio-temporal representations that is then decoded for image synthesis. For this, we use a direct training algorithm that computes loss on the membrane potential of the output layer and back-propagates it by using a sigmoid approximation of the neuron's activation function to enable differentiability. The spiking autoencoders are benchmarked on MNIST and Fashion-MNIST and achieve very low reconstruction loss, comparable to ANNs. Then, spiking autoencoders are trained to learn meaningful spatio-temporal representations of the data, across the two modalities-audio and visual. We synthesize images from audio in a spike-based environment by first generating, and then utilizing such shared multi-modal spatio-temporal representations. Our audio to image synthesis model is tested on the task of converting TI-46 digits audio samples to MNIST images. We are able to synthesize images with high fidelity and the model achieves competitive performance against ANNs.


Compensatory arm reaching strategies after stroke: induced position analysis.
After stroke, movement patterns of the upper limb (UL) during functional arm reaching change to accommodate altered constraints. These compensatory movement control strategies do not, however, have a one-to-one mapping with posttraining outcomes. In this study, we quantify arm movement control strategies in unilateral and bilateral reaching tasks using induced position analysis. In addition, we assess how those strategies are associated with UL residual impairments and with functional improvement after a specific bilateral arm training intervention. Twelve individuals with chronic stroke were measured while reaching to a box as part of their pre- and posttesting assessments. Other measurements included the Fugl-Meyer Upper Extremity Assessment (FM), Modified Wolf Motor Function Test (WT), and the University of Maryland Arm Questionnaire for Stroke (UMAQS). We identified arm control strategies that did not differ between unilateral and bilateral tasks but did differ by FM impairment level and by predicted gains in WT but not UMAQS. Increased shoulder relative to elbow moment contribution was associated with less impairment and greater gains of speed in functional tasks. These results suggest that one goal of training to achieve better outcomes may be to decrease the abnormal coupling of the shoulder and elbow.


[REVIEW OF PSYCHODYSLEPTICS: I. CLASSIFICATION OF PSYCHODYSLEPTICS].
The discovery of new dysleptic drugs has prompted the present review of these substances which influence neuropsychic activity. It is possible to divide dysleptics into two categories: under the first heading fall mescaline, LSD-25, psilocybine, adrenochrome, bufotenine and dimethyltryptamin; the other group includes Ditran, Butoxamine, WH-4849, and AHR-379. The place of Sernyl could not be ascertained and it might well constitute a class by itself. The mescaline type of reaction is mainly characterized by the induction of perceptual distortions without alteration of the state of consciousness, whereas the Ditran type reaction is one of confusion with postexperimental amnesia. Electroencephalographic recordings support this classification: lowering of amplitude, acceleration of rhythm and desynchronization were noted with the first group; and slowing of rhythm and slow waves similar to those seen during the onset of sleep, with the other group.


In addition to the SH3 binding region, multiple regions within the N-terminal noncatalytic portion of the cAMP-specific phosphodiesterase, PDE4A5, contribute to its intracellular targeting.
The long cyclic AMP (cAMP)-specific phosphodiesterase isoform, PDE4A5 (PDE4A subfamily isoform variant 5), when transiently expressed in COS-7 cells, was shown in subcellular fractionation studies to be associated with both membrane and cytosol fractions, with immunofluorescence analyses identifying PDE4A5 as associated both with ruffles at the cell margin and also at a distinct perinuclear localisation. Deletion of the first nine amino acids of PDE4A5 (1) ablated its ability to interact with the SH3 domain of the tyrosyl kinase, LYN; (2) reduced, but did not ablate, membrane association; and (3) disrupted the focus of PDE4A5 localisation within ruffles at the cell margin. This deleted region contained a Class I SH3 binding motif of similar sequence to those identified by screening a phage display library with the LYN-SH3 domain. Truncation to remove the PDE4A5 isoform-specific N-terminal region caused a further reduction in membrane association and ablated localisation at the cell margin. Progressive truncation to delete the PDE4A long isoform common region and then the long isoform-specific UCR1 did not cause any further change in membrane association or intracellular distribution. However, deletion up to the super-short form splice junction generated an entirely soluble 'core' PDE4A species. We propose that multiple sites in the N-terminal noncatalytic portion of PDE4A5 have the potential to associate with intracellular structures and thus define its intracellular localisation. At least two such sites lie within the PDE4A5 isoform-specific N-terminal region and these appear to be primarily responsible for targeting PDE4A5 to, and organising it within, the cell margin; one is an SH3 binding motif able to interact with LYN kinase and the other lies within the C-terminal portion of the PDE4A5 unique region. A third membrane association region is located within the N-terminal portion of UCR2 and appears to be primarily responsible for targeting to the perinuclear region. Progressive N-terminal truncation, to delete defined regions of PDE4A5, identified activity changes occurring upon deletion of the SH3 binding site region and then upon deletion of the membrane association site region located within UCR2. This suggests that certain of these anchor sites may not only determine intracellular targeting but may also transduce regulatory effects on PDE4A5 activity.


Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience.
To evaluate efficacy and toxicity of radio-chemotherapy (RCT) and MR-guided pulsed-dose-rate (PDR) adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). Between 2007 and 2014 85 patients with FIGO stage 1B1 N+ or ≥ 1B2 cervical cancer were treated with RCT+ IGABT. The treatment consisted of a pelvic± paraaortic external beam radiotherapy (EBRT) (45-50.4 Gy ± 10 Gy boost to primary tumor and/or to pathologic lymph nodes) with concurrent cisplatin followed by 25-35 Gy of PDR IGABT in 30-50 pulses. The ratio of 3D-CFRT/IMRT was 61/24 patients. Dose-volume parameters of high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and D2cm(3) organs at risk (OARs) were reported. Local control (LC), cancer-specific survival (CCS) and overall survival (OS) were analyzed actuarially and morbidity crude rates were scored using CTCAEv4.0. Mean follow-up was 36 months (range 6-94). The mean D90 and D98 for HR-CTV was 84.4 ± 9 Gy and 77 ± 8.1 Gy, while for IR-CTV was 69.1 ± 4.3 Gy and 64.8 ± 4.3 Gy, respectively. The mean D2cm(3) for OARs was the following: bladder: 77.3 ± 10.5 Gy, rectum: 65 ± 6.8 Gy, sigmoid: 63 ± 7.9 Gy and intestine: 64.0 ± 9.1 Gy. Three year LC, CSS and OS were: 94%, 85% and 81%. The three-year regional- and distant control rates were 95% and 74%. Node negative patients had significantly higher three-year CSS (100 vs. 72%, p = 0.016) and OS (92 vs. 72%, p = 0.001) compared to node positive ones. Three-year actuarial late Grade ≥ 3 morbidity was the following: GI: 8%, GU: 5%, Vaginal: 8%. The frequency of Grade ≥ 3 hematological toxicities including anemia/leukopenia/neutropenia/thrombocytopenia were 8.6%/34.7%/24.3%/24.3%, respectively. This large mono-institutional experience builds up further evidences that IGABT in conjunction with RCT should be the standard of care for patients suffering LACC.


Leaf litter decomposition rates increase with rising mean annual temperature in Hawaiian tropical montane wet forests.
Decomposing litter in forest ecosystems supplies nutrients to plants, carbon to heterotrophic soil microorganisms and is a large source of CO2 to the atmosphere. Despite its essential role in carbon and nutrient cycling, the temperature sensitivity of leaf litter decay in tropical forest ecosystems remains poorly resolved, especially in tropical montane wet forests where the warming trend may be amplified compared to tropical wet forests at lower elevations. We quantified leaf litter decomposition rates along a highly constrained 5.2 °C mean annual temperature (MAT) gradient in tropical montane wet forests on the Island of Hawaii. Dominant vegetation, substrate type and age, soil moisture, and disturbance history are all nearly constant across this gradient, allowing us to isolate the effect of rising MAT on leaf litter decomposition and nutrient release. Leaf litter decomposition rates were a positive linear function of MAT, causing the residence time of leaf litter on the forest floor to decline by ∼31 days for each 1 °C increase in MAT. Our estimate of the Q 10 temperature coefficient for leaf litter decomposition was 2.17, within the commonly reported range for heterotrophic organic matter decomposition (1.5-2.5) across a broad range of ecosystems. The percentage of leaf litter nitrogen (N) remaining after six months declined linearly with increasing MAT from ∼88% of initial N at the coolest site to ∼74% at the warmest site. The lack of net N immobilization during all three litter collection periods at all MAT plots indicates that N was not limiting to leaf litter decomposition, regardless of temperature. These results suggest that leaf litter decay in tropical montane wet forests may be more sensitive to rising MAT than in tropical lowland wet forests, and that increased rates of N release from decomposing litter could delay or prevent progressive N limitation to net primary productivity with climate warming.


Physico-chemical properties of low density lipoproteins in normolipidemic Asian Indian men.
The present study investigated whether a predisposition to high frequency of small, dense low density lipoproteins (LDL) could be an additional coronary risk factor in migrant Asian Indians. Ninety-three normolipidemic (fasting plasma cholesterol levels < or = 240 mg/dl and triglyceride levels < or = 250 mg/dl) adult Asian Indian men residing in the U.S. were compared to a group of 59 Caucasian men for the prevalence of LDL electrophoretic patterns A and B (size of major LDL peak > or = 255 A for LDL pattern A and < 255 A for LDL pattern B). Compared to the Caucasians, the Asian Indians had larger LDL size (mean +/- SD; 260.1 +/- 12.8 A vs 267.7 +/- 11.4 A, respectively; p = 0.0002), an increased frequency of LDL pattern A (59% vs 85%, respectively) and a lower frequency of LDL pattern B (41% vs 15%, respectively) (p = 0.0005). The difference in LDL size in the two study groups persisted after adjusting for the various confounding variables, such as age, plasma triglycerides, high-density lipoprotein cholesterol and dietary habits. We conclude that compared to Caucasians, Asian Indian men have larger LDL particles and a lower prevalence of LDL phenotype B in the presence of normolipidemia. Therefore, we exclude a genetic predisposition to atherogenic LDL phenotype as a factor contributing to the high incidence of coronary heart disease in migrant Asian Indians.


Retroviruses and microtubule-associated motor proteins.
Retroviruses are obligate intracellular parasites of eukaryotic cells. After reverse transcription, the viral DNA contained in the preintegration complex is delivered to the nucleus of the host cell, where it integrates. Before reaching the nucleus, the incoming particle and the preintegration complex must travel throughout the cytoplasm. Likewise, the newly synthesized viral proteins and viral particles must transit the cytoplasm during exit. The cytoplasm is a crowded environment, and simple diffusion is difficult. Therefore, viruses have evolved to utilize the cellular mechanisms of movement through the cytoplasm, where microtubules are the roads, and the ATP-dependent motors dynein and kinesin are the vehicles for retrograde and anterograde trafficking. This review will focus on how different retroviruses (Mazon-Pfizer monkey virus, prototype foamy virus, bovine immunodeficiency virus, human immunodeficiency virus type 1, and murine leukemia virus) have subjugated the microtubule-associated motor proteins for viral replication. Although there have been advances in our understanding of how retroviruses move along microtubules, the strategies are different among them. Thus, a better understanding of the mechanisms used by each retrovirus to functionally subvert microtubule motor proteins will provide important clues in the design of new antiretroviral drugs that can specifically disrupt intracellular viral trafficking.