Symptom-related emergency department visits and hospital admissions during ambulatory cancer treatment.
People with cancer experience symptoms related to the disease and treatments. Symptom distress has a negative impact on quality of life (QoL). Attending to symptoms and side effects of treatment promotes safe and effective delivery of therapies and may prevent or reduce emergency department visits (EDVs) and unplanned hospital admissions (HAs). There is limited evidence examining symptom-related EDVs or HAs (sx-EDV/HAs) and interventions in ambulatory oncology patients. To examine factors associated with sx-EDV/HAs in ambulatory oncology patients receiving chemotherapy and/or radiation. This secondary analysis used data from a randomized controlled trial of ambulatory oncology patients (n = 663) who received the web-based Electronic Self-Report Assessment – Cancer intervention (symptom self-monitoring, tailored education, and communication coaching) or usual care with symptom self-monitoring alone. Group differences were described by summary statistics and compared by t test. Factors associated with the odds of at least 1 sx-EDV/HA were modeled using logistic regression. 98 patients had a total of 171 sx-EDV/HAs with no difference between groups. Higher odds of at least 1 sx-EDV/HA were associated with socioeconomic and clinical factors. The multivariable model indicated that work status, education level, treatment modality, and on-treatment Symptom Distress Scale-15 scores were signifcantly associated with having at least 1 sx-EDV/HA. This is a secondary analysis not sized to determine cause and effect. The results have limited generalizability. Most patients did not experience a sx-EDV/HA. Demographic and clinical factors predicted a sx-EDV/HA.


Virulence of the Bio-Control Fungus Purpureocillium lilacinum Against Myzus persicae (Hemiptera: Aphididae) and Spodoptera frugiperda (Lepidoptera: Noctuidae).
Eco-friendly entomopathogenic fungi are widely used to control agricultural insect pests. Purpureocillium lilacinum (Thom.) Luangsa-ard et al. (Hypocreales: Ophiocordycipitaceae) is a nematophagous fungus used for the bio-control of destructive root-knot nematodes. However, its insecticidal activities against agricultural insect pests haven't been widely studied. In this study, P. lilacinum PL-1 was isolated from soil (Hefei, China) and identified by molecular and morphological analyses. The growth rate, spore production, proteinase, and chitinase activities of the isolate were analyzed. Virulence tests against green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae) and fall armyworm (FAW), Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) were performed. The median lethal concentration (LC50) and median lethal time (LT50) against aphids (via immersion) and LT50 against FAW (via injection) were determined. FAW eggs immersed in aqueous conidia suspension were infected after 60 h. Differentially expressed genes (DEGs) in the infection of FAW larvae by P. lilacinum were analyzed by quantitative reverse transcription PCR. The significantly upregulated DEGs include FAW immune genes (antimicrobial peptides, C-type lectins, lysozymes, prophenoloxidase, and peptidoglycan recognition proteins) and fungal pathogenic genes (ligase, chitinase, and hydrophobin). Our data demonstrate that P. lilacinum can be used as an entomopathogenic fungus against agricultural insect pests.


From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung.
Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM). The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung. The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity. In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.


Ethanol exposure affects glial fibrillary acidic protein gene expression and transcription during rat brain development.
Exposure to ethanol during fetal development reduces the astroglial-specific marker glial fibrillary acidic protein (GFAP) and its mRNA levels in brains of fetal rats and in radial glia in primary culture, affecting the proliferation and differentiation of astrocytes. The objectives of this study were to evaluate the possible effect of ethanol on GFAP mRNA levels in astrocytes and to investigate the molecular mechanism(s) involved in ethanol-induced changes in GFAP expression by analyzing the GFAP transcription rate, GFAP mRNA stability, and GFAP DNA methylation. We show here that prenatal exposure to ethanol reduces significantly GFAP immunoreactivity and its mRNA levels in both astrocytes in primary culture and brains of pups from alcohol-fed mothers. Runoff experiments from nuclei of astrocytes indicate that ethanol exposure decreases GFAP transcription rate significantly and reduces GFAP mRNA stability slightly. DNA methylation analysis indicates that prenatal ethanol exposure induces a hypermethylated state of the GFAP DNA in fetal brains. Methylation-mediated repression of GFAP transcription could be a mechanism involved in ethanol-induced reduction of GFAP expression. Ethanol-induced alterations in GFAP expression and astroglial development may underlie the CNS dysfunctions observed after prenatal alcohol exposure.


Immunogold-silver staining of cells recovered by bronchoalveolar lavage. A report of three cases demonstrating its value in the diagnosis of pulmonary involvement in hematologic malignancies.
The diagnosis of pulmonary involvement in hematologic malignancies (PHM) has traditionally necessitated large specimens (usually invasive or surgically obtained biopsies). The development of reliable immunocytologic identification techniques allows diagnosis on noninvasively obtained cellular material, including bronchoalveolar lavage (BAL) fluid. Since 1985, 12 such cases have been reported. Three cases of B-cell-related PHM were diagnosed by means of BAL fluid cellular analysis using the immunogold-silver staining technique. This is the first report showing immunogold-silver staining to be a reliable immunocytochemical identification technique for monoclonal B-cell populations recovered by BAL.


Blood-Based Treatments for Severe Dry Eye Disease: The Need of a Consensus.
The use of blood-based eye drops as therapy for various diseases of the ocular surface has become increasingly popular in ophthalmic practice during recent years. The rationale for their use is based on the promotion of cellular proliferation and migration thanks to the supply of metabolically active substances, in particular growth factors. Blood-derived eye drops have been used for the treatment of several ocular surface disorders, such as dry eye disease, corneal ulcer, persistent epithelial defect, neurotrophic keratitis, ocular surface burn, recurrent corneal erosion, and limbal stem-cell deficiency. Both autologous (from patients themselves) and heterologous (from adult donors or from cord blood sampled at birth)-derived products exist, and each source has specific pros and cons. Despite an extensive literature, several issues are still under debate and the aim of this manuscript is to review the indications, preparation methods and storage, characterization of content, rationale for clinical outcomes, patient stratification, length of treatment, and rationale for repeated treatments at disease relapse. A rationale based on a "5 Ws and 2 Hs" protocol is proposed as a way of thinking, with the attempt to clarify Who, Why, When, Where, What, and How to use these treatment options.


Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin.
In this study, P-glycoprotein (P-gp) mediated efflux of simvastatin (SV), simvastatin acid (SVA), and atorvastatin (AVA) and inhibition of P-gp by SV, SVA, and AVA were evaluated to assess the role of P-gp in drug interactions. P-gp mediated efflux of SV, SVA, and AVA was determined by directional transport across monolayers of LLC-PK1 cells and LLC-PK1 cells transfected with human MDR1. Inhibition of P-gp was evaluated by studying the vinblastine efflux in Caco-2 cells and in P-gp overexpressing KBV1 cells at concentrations of SV, SVA, and AVA up to 50 microM. Directional transport studies showed insignificant P-gp mediated efflux of SV, and moderate P-gp transport [2.4-3.8 and 3.0-6.4 higher Basolateral (B) to Apical (A) than A to B transport] for SVA and AVA, respectively. Inhibition studies did not show the same trend as the transport studies with SV and AVA inhibiting P-gp (IC50 -25-50 microM) but SVA not showing any inhibition of P-gp. The moderate level of P-gp mediated transport and low affinity of SV, SVA, and AVA for P-gp inhibition compared to systemic drug levels suggest that drug interactions due to competition for P-gp transport is unlikely to be a significant factor in adverse drug interactions. Moreover, the inconsistencies between P-gp inhibition studies and P-gp transport of SV, SVA, and AVA indicate that the inhibition studies are not a valid means to identify statins as Pgp substrates.


Psychological correlates of nonspecific skin conductance responses.
Previous research has indicated that the frequency of skin conductance responses without external stimulation or motor activity is a reliable indicator of psychophysiological states and traits. Some authors have suggested that cognitions elicit nonspecific skin conductance responses. These cognitions may resemble the stimuli that evoke a specific skin conductance response. In a within subjects design (n = 31 graduate students) the onset of nonspecific skin conductance responses triggered a signal for the subject to rate cognitions on several indices. These ratings ("absent" to "fully present") were compared with samples in the absence of phasic electrodermal activity. The subjects' current concerns, negative emotion, subjective arousal, and inner speech were rated to be significantly more intense at the time of nonspecific skin conductance responses compared to electrodermal nonresponding periods. Cognitive processes seem to be concomitants of nonspecific skin conductance responses.


Nanocrystal film patterning by inhibiting cation exchange via electron-beam or X-ray lithography.
In this Letter we report patterning of colloidal nanocrystal films that combines direct e-beam (electron beam) writing with cation exchange. The e-beam irradiation causes cross-linking of the ligand molecules present at the nanocrystal surface, and the cross-linked molecules act as a mask for further processing. Consequently, in the following step of cation exchange, which is performed by directly dipping the substrate in a solution containing the new cations, the regions that have not been exposed to the electron beam are chemically transformed, while the exposed ones remain unchanged. This selective protection allows the design of patterns that are formed by chemically different nanocrystals, yet in a homogeneous nanocrystal film. Spatially resolved compositional analysis by energy-dispersive X-ray spectroscopy (EDS) corroborates that the selective exchange occurs only in the nonirradiated regions. We demonstrate the utility of this lithography approach by fabricating conductive wires and luminescent patterns in CdSe/CdS nanocrystal films by converting nonirradiated regions to Cu2-xSe/Cu2-xS. Furthermore, we show that X-ray irradiation too can lead to protection from cation exchange.


Dopaminergic and cholinergic muscarinic receptor effects of L-alphacetylmethadol (LAAM) and its metabolites.
In isolated rat hearts L-alphacetylmethadol (LAAM) produced a concentration-dependent decrease in the spontaneous beating rate. This effect was completely prevented by 1.0 microM atropine. Chronic treatment of rats with LAAM increased the number of striatal dopamine receptors measured by [3H]spiroperidol binding. The affinity of these binding sites for [3H]spiroperidol was unchanged by LAAM treatment. There were no significant changes in the number or affinity of binding sites for the labeled muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) with chronic LAAM treatment. The ability of LAAM, nor-LAAM, or dinor-LAAM to antagonize the binding of [3H]spiroperidol (40 pM) or [3H]QNB (125 pM) to striatal membrane fragments was tested. The measured affinity constants for LAAM and metabolites were 100-3000 times higher than the affinity constants of unlabeled spiroperidol at [3H]spiroperidol binding sites. The affinity constants of LAAM and metabolites at muscarinic binding sites were 10-20 times higher than pilocarpine and 5000-8000 times higher than atropine. These results suggest that LAAM can produce some of its effects by acting as a weak agonist at muscarinic receptor sites.


"Making it real" time.
It has been 30 years since the first description of the polymerase chain reaction (PCR)--corresponding, coincidentally, with the year of the first issue of BioTechniques. Ensuing decades have seen remarkable advances in this revolutionary technique. Central to these approaches was the creation of paradigms for monitoring the progress of PCR amplification in real time. One of these seminal reports appeared in BioTechniques in 1997, establishing the double-strand-specific dye SYBR Green as a workhorse tool for continuous monitoring of DNA amplification.


Validation of a MS Based Proteomics Method for Milk and Egg Quantification in Cookies at the Lowest VITAL Levels: An Alternative to the Use of Precautionary Labeling.
The prevalence of food allergy has increased over the last decades and consequently the food labeling policies have improved over the time in different countries to regulate allergen presence in foods. In particular, Reg 1169 in EU mandates the labelling of 14 allergens whenever intentionally added to foods, but the inadvertent contamination by allergens still remains an uncovered topic. In order to warn consumers on the risk of cross-contamination occurring in certain categories of foods, a precautionary allergen labelling system has been put in place by food industries on a voluntary basis. In order to reduce the overuse of precautionary allergen labelling (PAL), reference doses and action limits have been proposed by the Voluntary Incidental Trace Allergen Labelling VITAL project representing a guide in this jeopardizing scenario. Development of sensitive and reliable mass spectrometry methods are therefore of paramount importance in this regard to check the contamination levels in foods. In this paper we describe the development of a time-managed multiple reaction monitoring (MRM) method based on a triple quadrupole platform for milk and egg quantification in processed food. The method was in house validated and allowed to achieve levels of proteins lower than 0.2 mg of total milk and egg proteins, respectively, in cookies, challenging the doses recommended by VITAL. The method was finally applied to cookies labeled as milk and egg-free. This method could represent, in perspective, a promising tool to be implemented along the food chain to detect even tiny amounts of allergens contaminating food commodities.


Cyclophilin-A is bound through its peptidylprolyl isomerase domain to the cytoplasmic dynein motor protein complex.
Although cyclophilin A (CyP-A) is a relatively abundant small immunophilin present in the cytoplasm of all mammalian cells, its general function(s) in the absence of the immunosuppressant drug cyclosporin A is not known. In contrast, the high molecular weight hsp90-binding immunophilins appear to play a role in protein trafficking in that they have been shown to link glucocorticoid receptor-hsp90 and p53.hsp90 complexes to the dynein motor protein for retrograde movement along microtubules. These immunophilins link to cytoplasmic dynein indirectly through the association of the immunophilin peptidylprolyl isomerase (PPIase) domain with dynamitin, a component of the dynein-associated dynactin complex (Galigniana, M. D., Harrell, J. M., O'Hagen, H. M., Ljungman, M., and Pratt, W. B. (2004) J. Biol. Chem. 279, 22483-22489). Here, we show that CyP-A exists in native heterocomplexes containing cytoplasmic dynein that can be formed in cell-free systems. Prolyl isomerase activity is not required for forming the dynein complex, but the PPIase domain fragment of FKBP52 blocks complex formation and CyP-A binds to dynamitin in a PPIase domain-dependent manner. CyP-A heterocomplexes containing tubulin and dynein can be formed in cytosol prepared under microtubule-stabilizing conditions, and CyP-A colocalizes in mouse fibroblasts with microtubules. Colocalization with microtubules is disrupted by overexpression of the PPIase domain fragment. Thus, we conclude that CyP-A associates in vitro and in vivo with the dynein/dynactin motor protein complex and we suggest that CyP-A may perform a general function related to the binding of cargo for retrograde movement along microtubules.


Molecular Diversity and Genetic Relatedness of Candida albicans Isolates from Birds in Hungary.
The molecular epidemiology of Candida albicans infections in animals has been rarely studied. In this study, multilocus sequence typing was used to characterise the genetic diversity and population structure of 24 avian origin C. albicans isolates collected from different birds with candidiasis and compared to human isolates. Fourteen diploid sequence types (DSTs) including six new DSTs were determined. Cluster analysis revealed that isolates grouped into 8 clades. Bird isolates mainly belonged to minor clades and Clade 15 with DST 172 was the most common (11 isolates; 45.8%). The remaining isolates were clustered into Clade 7 (5 isolates; 20.8%), Clade 10 (4 isolates; 16.6%), Clade 8 (2 isolates; 8.3%), Clade 4 (1 isolate; 4.2%) and Clade 16 (1 isolate; 4.2%). Unweighted pair group method with arithmetic averages (UPGMA) and eBURST analyses showed that the genetic construction of avian origin C. albicans population is fairly diverse. Although species-specific lineages were not found, some degree of separation in the evolution of bird and human strains could be observed.


Impact of health management, health treatments, and zilpaterol hydrochloride supplementation on carcass quality, color, and palatability traits in heifers.
Two hundred sixty-eight strip loins were collected from heifers fed at Oklahoma State University in Stillwater, OK. In Exp. 1, heifers (n = 127) were assigned to 1 of 3 health management treatment groups: antimicrobial administrations were given based on standard feedlot protocol (SFP) or ruminal temperature (RT) or given a metaphylactic treatment of tulathromycin (MT) followed by visual assessment (VA). In Exp. 2, heifers (n = 155) were assigned to the same treatment groups as above and were supplemented zilpaterol hydrochloride (ZH) or control (CON). Three steaks were collected from each strip loin, 1 each for retail display, sensory evaluation, and Warner-Bratzler shear force (WBSF). Color was evaluated from the retail display steak using a trained color panel and objectively using a HunterLab Miniscan XE. An Instron Universal Testing Machine with a Warner-Bratzler head was used for evaluation of instrumental tenderness, and a trained sensory panel was used to assess palatability traits. Heifers treated by VA had the least number of antimicrobial administrations and lowest yield grade and also had the lightest HCW (P < 0.05) compared with the heifers treated by the other health management protocols. There were no subjective color attribute differences or sensory panel differences (P > 0.05) across all health management systems or antimicrobial administrations. There were no differences in carcass and performance traits for any antimicrobial administrations treatment groups (P > 0.05). Heifers who had 0 or 1 antimicrobial administrations had lower (P < 0.05) a* (redness/greenness: positive values = red and negative values = green), and b* (yellowness/blueness: positive values = yellow and negative values = blue) values compared with those who had 2 antimicrobial administrations. In Exp. 2, heifers treated by VA had the least number (P < 0.05) of antimicrobial administrations when compared with MT and RT. Health management group did not have any other effects on carcass, sensory, or color attributes. Zilpaterol hydrochloride supplementation caused a decrease (P < 0.05) in internal fat and yield grade, but no interactions were observed between the number of antimicrobial administrations and ZH supplementation. With the supplementation of ZH, WBSF significantly increased (P < 0.05). At the end of retail display, the control group had a greater (P < 0.05) surface discoloration when compared with the ZH group. Treatment and detection of bovine respiratory diseases (BRD) is critical to the industry economically and results from this study show that different methods can be used to detect BRD without dramatically impacting carcass, sensory, and retail case life characteristics.


A task failure has no effect on the electromechanical delay of the peroneus longus.
Ankle inversion injuries represent the most common trauma sustained by athletes. Muscle fatigue from activity may contribute to a delay in the response of the ankle proprioceptors and dynamic restraints during unexpected inversion. The purpose of this investigation was to determine if the electromechanical delay (EMD) of the peroneus longus is influenced by a task failure exercise. Sixteen subjects (age 20 +/- 1.1 y; mass 71.6 +/- 12.5 kg; height 173.0 +/- 8.7 cm; 9 male, 1 female) with no lower extremity injuries reported for data collection. Data were collected from each subject's dominant leg using surface electromyography (EMG). Electrodes were applied over the peroneus longus (PL) using a standard protocol. A stimulating electrode was applied to the common peroneal nerve. Subjects were placed in a monopedal stance on a force platform. A low amplitude, short duration stimulus was applied to the common peroneal nerve. The EMG was used to determine timing of the M wave and the force platform was used to determine the onset of foot pronation. Once 6 trials were recorded, subjects completed 2 sets of an isotonic activity that isolated the peroneals. The task was completed to failure for each set. Immediately following the task failure exercise, subjects returned to the force platform for 6 additional trials recorded as before. Analysis of data was performed by determining the onset of the M wave as the beginning of positive EMG activity following the end of the imposed stimulus response. This point was superimposed on the force platform curve and the point at which a 10 N.m force change occurred was used to calculate the EMD (time difference between the force platform indicator and the M wave indicator). Average EMD prior to the task failure exercise was 13.35 +/- 3.47 ms. Following the task failure exercise, the average EMD was 12.67 +/- 3.86 ms. A paired samples t test revealed no significant differences with regard to EMD between pre- and post-task failure exercise for the PL (p = 0.448). We concluded that the task failure exercise did not affect the electromechanical delay of the PL.


Osteosarcoma in a cow.
A mass involving the maxilla of a cow was determined to be an osteosarcoma. Microscopically, the mass was composed of plump pyriform cells aligned along thin trabeculae of osteoid. Osteosarcoma rarely develops in large animal species, but when it does, it is usually found in the skull and must be differentiated from more common diseases, such as actinomycosis and tooth abscesses.


A Nomogram for Predicting Laparoscopic and Endoscopic Cooperative Surgery during the Endoscopic Resection of Subepithelial Tumors of the Upper Gastrointestinal Tract.
Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper gastrointestinal (GI) subepithelial tumors (SET) increases. For relatively safer removal of upper GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery. This study aimed to analyze the outcome of endoscopic resection for SETs and develop a prediction model for the need for laparoscopic and endoscopic cooperative surgery (LECS) during the procedure. We retrospectively analyzed 123 patients who underwent endoscopic resection for upper GI SETs between January 2012 and December 2020 at our institution. Intraoperatively, they underwent ESD or submucosal tunneling endoscopic resection (STER). ESD and STER were performed in 107 and 16 patients, respectively. The median age was 55 years, and the average tumor size was 1.5 cm. En bloc resection was achieved in 114 patients (92.7%). The median follow-up duration was 242 days without recurrence. Perforation occurred in 47 patients (38.2%), and 30 patients (24.4%) underwent LECS. Most perforations occurred in the fundus. Through multivariable analysis, we built a nomogram that can predict LECS requirement according to tumor location, size, patient age, and sex. The prediction model exhibited good discrimination ability, with an area under the curve (AUC) of 0.893. Endoscopic resection is a noninvasive procedure for small upper-GI SETs. Most perforations can be successfully managed endoscopically. The prediction model for LECS requirement is useful in treatment planning.


New Evidence to Guide Ectopic Pregnancy Diagnosis and Management.
Ectopic pregnancy is a leading source of morbidity and mortality in pregnancy, accounting for 1% to 2% of all pregnancies. Timely diagnosis and management of these abnormal gestations are vital to patient safety. The objective of this study was to describe recent evidence in the risk factors, diagnosis, and management of ectopic pregnancy. Comprehensive review of the published literature. Recent literature describes newly identified risk factors for ectopic pregnancy, particularly those specific to assisted reproduction. Furthermore, evidence mounts for the utility of endometrial sampling for the diagnosis of pregnancy location, allowing a significant proportion of women to avoid methotrexate by diagnosing failing intrauterine pregnancies instead. Finally, recent, high-level evidence supports (in women with normal contralateral fallopian tubes) the equivalence of salpingectomy and salpingostomy regarding rates of subsequent intrauterine pregnancy and recurrent ectopic pregnancy. While serial serum human chorionic gonadotropin levels and transvaginal ultrasound are the mainstays of ectopic pregnancy diagnosis, recent publications revisit the utility of endometrial sampling in diagnosing pregnancy location, using manual vacuum aspiration instead of the criterion-standard dilation and curettage. Expectant management of ectopic pregnancies is the subject of ongoing research, and in the meantime, treatment remains medical or surgical (dependent on clinical parameters and patient preference); salpingostomy and salpingectomy provide equivalent subsequent pregnancy outcomes in women with contralateral fallopian tubes in place.


Nutrition & Exercise Interventions in Pediatric Patients with Brain Tumors: A Narrative Review.
Brain tumors have been the most common pediatric solid tumor and leading cause of morbidity and mortality. Improved survival emphasizes the importance of adverse treatment effects especially related to nutrition and exercise. Although studies have examined nutrition and exercise outcomes, few randomized trials exist. This narrative review included a systematic literature search with analysis of controlled or single group studies examining clinical and quality-of-life impact of nutrition or exercise interventions. Seven articles were included. Three nutrition studies demonstrated improvement with proactive feeding tubes, nutritional supplementation, and nutritional status. Two exercise studies showed improvement in measures of fitness and neuroanatomy with exercise in pediatric brain tumor survivors; two cohort studies demonstrated a link between quality of life and physical activity. Preliminary studies show nutrition and exercise may improve physical well-being and quality of life, suggesting future controlled studies are warranted to inform clinical care of children with brain tumors.


Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018-2019 Season.
The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1-42 after 2018-2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare. We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8-21 and 1-42 postvaccination as risk windows and days 43-84 as control window. The VSD conducted chart-confirmed analyses. Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99-3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78-2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92-2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70-1.79) risk windows. The VSD's chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06-15.99). The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.


Investigating the Immediate and Cumulative Effects of Isometric Squat Exercise for Different Weight Loads on Intraocular Pressure: A Pilot Study.
The execution of resistance exercise against heavy loads promotes an acute intraocular pressure (IOP) rise, which has detrimental effects on ocular health. However, the effect of load on the IOP behavior during exercise remains unknown due to technical limitations. IOP monitoring during isometric squat exercise permits assessment of IOP behavior during physical effort. Second, greater loads will induce a higher IOP rise. Randomized cross-sectional study. Level 2. Twenty-six young adults (13 women, 13 men) performed an isometric squat exercise against 3 loads relative to their maximum capacity (low, medium, and high). IOP was measured before, during (1 measurement every 6 seconds), and after exercise (10 seconds of recovery). There was a progressive IOP rise during exercise, which was dependent on the load applied (Bayes factor10 >100). Higher IOP values were found in the high load condition in comparison with the medium (mean IOP difference = 1.5 mm Hg) and low (mean IOP difference = 3.1 mm Hg) conditions, as well as when the medium load was compared with the low load condition (mean IOP difference = 1.6 mm Hg). Men reached higher IOP values in comparison with women during the last measurements in the high load condition. Ten seconds of recovery were enough to obtain IOP values similar to baseline levels. Isometric squat exercise induces an immediate and cumulative IOP elevation, which is positively associated with the load applied. These IOP increments return to baseline values after 10 seconds of recovery, and men demonstrate a more accentuated IOP rise in comparison with women when high levels of effort are accumulated. These findings may help in better management of different ocular conditions and highlight the importance of an individualized exercise prescription in clinical populations.


[Colonic motility in the irritable bowel syndrome].
The importance of colonic motor disorders during the irritable bowel syndrome is recognized, but, paradoxically, their description has yet to be perfected. Among the fundamental questions that remain unanswered, three are of prime importance: a) are there one or more specific disturbances in basal colonic motility? b) can specific motor disorders be induced by certain situations, for instance, during stress? c) is there any real relationship between clinical symptoms and coexisting motor disorders? The answers to these questions are full of ambiguities; this may be explained by the difficulty with which methods of investigation are performed as well as the heterogeneous character of the disorders. Presently, recording colonic myoelectric activity over a 24 hour period or more might prove to be useful in increasing our knowledge on motor disorders. It is not at all certain that a specific basal abnormality exists and the results of the effects of stress vary according to the methods used. Segmental hyperactivity in painful constipation, abnormal colonic response to alimentation in the case of painful bloating, and propulsive hyperactivity with absence or decrease in the "sigmoid brake" during painless diarrhea have been noted on basal motor activity recordings during sleep and after meals. Myoelectric disorders, however, are seen in only two-thirds of patients with intestinal functional disorders. "Sensitivity", personality, or other disorders, and particularly, intestinal disorders, can contribute to explain the pathophysiology of "irritable bowels" in which the role of colonic disorders has yet to be shown.


Defining intrahepatic biliary anatomy in living liver transplant donor candidates at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2-weighted MR cholangiography.
To compare three-dimensional (3D) mangafodipir trisodium-enhanced T1-weighted magnetic resonance (MR) cholangiography with conventional T2-weighted MR cholangiography for depiction and definition of intrahepatic biliary anatomy in liver transplant donor candidates. One hundred eight healthy liver transplant donor candidates were examined with two MR cholangiographic methods. All candidates gave written informed consent, and the study was approved by the institutional review board. First, breath-hold transverse and coronal half-Fourier single-shot turbo spin-echo and breath-hold oblique coronal heavily T2-weighted turbo spin-echo sequences were performed. Second, mangafodipir trisodium-enhanced breath-hold fat-suppressed 3D gradient-echo sequences were performed through the ducts (oblique coronal plane) and through the entire liver (transverse plane). Interpretation of biliary anatomy findings, particularly variants affecting right liver lobe biliary drainage, and degree of interpretation confidence at both 3D mangafodipir trisodium-enhanced MR cholangiography and T2-weighted MR cholangiography were recorded and compared by using the Wilcoxon signed rank test. Then, consensus interpretations of both MR image sets together were performed. Intraoperative cholangiography was the reference-standard examination for 51 subjects who underwent right lobe hepatectomy. The McNemar test was used to compare the accuracies of the individual MR techniques with that of the consensus interpretation of both image sets together and to compare each technique with intraoperative cholangiography. Biliary anatomy was visualized with mangafodipir trisodium enhancement in all patients. Mangafodipir trisodium-enhanced image findings agreed with findings seen at combined interpretations significantly more often than did T2-weighted image findings (in 107 [99%] vs 88 [82%] of 108 donor candidates, P < .001). Confidence was significantly higher with the mangafodipir trisodium-enhanced images than with the T2-weighted images (mean confidence score, 4.5 vs 3.4; P < .001). In the 51 candidates who underwent intraoperative cholangiography, mangafodipir trisodium-enhanced imaging correctly depicted the biliary anatomy more often than did T2-weighted imaging (in 47 [92%] vs 43 [84%] donor candidates, P = .14), whereas the two MR imaging techniques combined correctly depicted the anatomy in 48 (94%) candidates. Mangafodipir trisodium-enhanced 3D MR cholangiography depicts intrahepatic biliary anatomy, especially right duct variants, more accurately than does conventional T2-weighted MR cholangiography.


A role for non-covalent SUMO interaction motifs in Pc2/CBX4 E3 activity.
Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins, which can increase the efficiency and specificity of the sumoylation process. In addition to covalent attachment of SUMO to target proteins, specific non-covalent SUMO interaction motifs (SIMs) that are generally short hydrophobic peptide motifs have been identified. Intriguingly, consensus SIMs are present in most SUMO E3s, including the polycomb protein, Pc2/Cbx4. However, a role for SIMs in SUMO E3 activity remains to be shown. We show that Pc2 contains two functional SIMs, both of which contribute to full E3 activity in mammalian cells, and are also required for sumoylation of Pc2 itself. Pc2 forms distinct sub-nuclear foci, termed polycomb bodies, and can recruit partner proteins, such as the corepressor CtBP. We demonstrate that mutation of the SIMs in Pc2 prevents Pc2-dependent CtBP sumoylation, and decreases enrichment of SUMO1 and SUMO2 at polycomb foci. Furthermore, mutational analysis of both SUMO1 and SUMO2 reveals that the SIM-interacting residues of both SUMO isoforms are required for Pc2-mediated sumoylation and localization to polycomb foci. This work provides the first clear evidence for a role for SIMs in SUMO E3 activity.


Effects of postnatal protein undernutrition on myelination in rat brain.
Pups were subjected, from birth, to protein undernutrition by feeding the lactating dams 8% casein (CS) or 8% soy protein (SP) diet up to weaning; the weanlings were fed the same diets until 6 weeks of age. At 3 and 6 weeks of age, myelin was isolated from the brains and characterized. The quantities of myelin and its content of cholesterol, galactolipids and phospholipids, were significantly depressed in the 8% CS and 8% SP groups but not when soy protein was fed at the same level as casein (25%) in the control. Furthermore, the severity of the deficits in myelination showed a differential pattern depending on the type of dietary protein fed. At weaning, the deficits with the 8% SP diet were 1.5-2.0-times greater than with the corresponding casein diet. A more pronounced retardation in the initiation, progression and capacity of myelination in postnatal soy protein undernutrition was indicated.


Continuous Wound Infiltration After Hallux Valgus Surgery.
Hallux valgus surgery is associated with significant early postoperative pain. The aim of this study was to investigate the use of continuous wound infiltration (CWI) with ropivacaine for pain management after hallux valgus surgery. In this prospective, randomized, double-blind, and placebo-controlled single-center trial, 50 patients undergoing distal metatarsal osteotomy for idiopathic hallux valgus were allocated to CWI with ropivacaine 2 mg/mL at a rate of 2 mL/h or placebo for 24 hours postoperatively. Average and peak pain levels on the verbal numeric rating scale (NRS; 1-10) during the first 48 hours after surgery were recorded as primary outcome parameters. Secondary outcome parameters included consumption of narcotics, clinical outcome, incidence of postoperative complications, and patient satisfaction. No significant difference in mean ( P = .596) and peak ( P = .353) postoperative pain level was found for CWI with either ropivacaine (mean NRS 1.9 ± 0.8; peak NRS 3.5 ± 2.0) or placebo (mean NRS 2.0 ± 0.7; peak NRS 3.9 ± 1.7) during the early postoperative course. Furthermore, no significant difference between both groups was detected regarding narcotic consumption ( P = .354) and all other secondary outcome parameters. Two severe complications (local dysesthesia with CWI, catheter accidentally fixed by a suture) and 5 catheter dislocations were observed. CWI with ropivacaine 2 mg/mL at a rate of 2 mL/h for 24 hours after hallux valgus surgery did not reduce postoperative pain level in an inpatient setting. Level I, prospective randomized trial.


Immunological responses to social stress: dependence on social environment and coping abilities.
Social interactions as a consequence of the social position represent stressful conditions for the individual. Manipulation of social conditions or forming long-term social hierarchies by colony aggregation allow to investigate the regulation of immune defense mechanisms under seminatural circumstances. The present paper describes the effects of dyadic social interaction in male rats with or without direct aggressive interactions on some indices of humoral and cellular immunity. In addition, for comparative and reference purposes, in one experiment the conventional stressor of inescapable footshock was used as well. Primary humoral immune response to sheep red blood cell antigen is suppressed by repeated experience of both defeat and inescapable footshock. At individual level the social stressor is as effective as the conventional stressor of inescapable footshock, less individual rats show suppression following the social than after the conventional stress. The social stressors, i.e. being exposed to a resident or intruder of the territory, facilitate lymphocyte proliferation in the spleen by the mitogen ConA and PHA independently of the presence or absence of direct aggressive interaction. Finally, the different social stressors have some impact on the lymphocyte subpopulation in the spleen. Social stimulation without aggressive interactions increases the relative number of T-helper cells, whereas defeat leads to an increase in the T-suppressor/cytotoxic subpopulation. The data suggest multiple and differential effects of social stress on immune system functioning in the rat. Individual characteristics of the coping with stress, the social environment, and the immune indices under investigation determine the magnitude and direction of the changes in immune functioning.


Coagulation System Disorders and Thrombosis Prophylaxis During Laparoscopic Fundoplications.
The aim of this study was to assess and recommend the optimal deep vein thrombosis (DVT) prophylaxis regimen during and after laparoscopic fundoplication according to the blood coagulation disorders and the rate of DVT in 2 patient groups, receiving different DVT prophylaxis regimens. This was a prospective randomized, single-center clinical study. The study population, 121 patients, were divided into 2 groups: group I received low-molecular-weight heparin 12 hours before the operation; group II received low-molecular-weight heparin only 1 hour before the laparoscopic fundoplication. Both groups received intermittent pneumatic compression during the entire procedure. Bilateral Doppler ultrasound to exclude DVT was performed before the surgery. Venous phase computed tomographic images were acquired from the ankle to the iliac tubercles on the third postoperative day to determine the presence and location of DVT. Hypercoagulation state was assessed by measuring the prothrombin fragment F1+2 (F1+2), the thrombin-antithrombin complex (TAT), and tissue factor microparticles activity (MP-TF) in plasma. The hypocoagulation effect was evaluated by measuring plasma free tissue factor pathway inhibitor (fTFPI). F1+2, TAT, and MP-TF indexes increased significantly, whereas fTFPI levels decreased significantly during and after laparoscopic fundoplication, when molecular-weight heparin was administered 12 hours before the operation. Computed tomography venography revealed peroneal vein thrombosis in 2 group I patients on the third postoperative day. Total postsurgical DVT frequency was 1.65%: 3.6% in group I, with no DVT in group II. Molecular-weight heparin and intraoperative intermittent pneumatic compression controls the hypercoagulation effect more efficiently when it is administered 1 hour before surgery: it causes significant reduction of F1+2, TAT, and MP-TF indexes and significant increases of fTFPI levels during and after laparoscopic fundoplication.


Asthma and rhinitis related to laboratory rats: use of a purified rat urinary allergen to study exposure in laboratories and the human immune response.
Using the major rat allergen as a model has made it possible to study both natural exposure and the human immune response to an important laboratory animal. The close correlation between positive skin tests to whole rat urine and IgE antibody to the major urinary allergen in this and previous studies supports the use of this protein as a model rat allergen. Measurements of airborne rat allergen confirm that the maximum levels are higher than those reported with pollen or mite allergens. However, it is possible that exposure to rat allergens is comparable to levels of exposure to cat salivary allergens in houses with cats. The clear implication is that the high levels of exposure are responsible for the fact that a large proportion of exposed individuals develop IgG antibodies. Our results suggest that the prevalence of IgG antibodies (not individual levels) in a group of workers would be a good guide to exposure. This leaves unresolved why some of the individuals who develop IgG ab also develop IgE ab and become at risk for developing asthmatic responses. Only part of this risk is related to atopy. A striking feature of all the studies on animal allergy is the close association between IgE ab and asthma. It appears clear that it is those immune responses that include IgE ab that are a risk factor for asthma. It is not sensible for anyone to remain consistently sick with asthma and continue working with laboratory animals because there are well documented examples of occupational asthma that has not resolved after ceasing exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular Detection and Characterization of Giardia duodenalis in Farmed Pigs in Three Provinces of Southern China.
Giardia duodenalis is a flagellated zoonotic parasite that can infect various animals and humans, causing economic losses in husbandry and detriments to public health. Although it has been reported in pigs worldwide, there are few reports on the prevalence and assemblages of G. duodenalis infection in pigs in China. In this study, the 396 pig fecal samples were randomly collected from seven farms in Zhejiang, Guangdong and Yunnan provinces in southern China, and were examined by means of the nested PCR amplification of β-giardin (bg), glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) for the detection of G. duodenalis. Overall, 21 fecal samples were positive for G. duodenalis, with a prevalence of 5.3%. Three risk factors are associated with G. duodenalis infection, namely, region, age and gender. Moreover, 13, six and two samples were successfully amplified at the bg, gdh and tpi gene loci, respectively. Three assemblages of G. duodenalis were identified, including assemblage E (n = 17), assemblage A (n = 3) and assemblage B (n = 1). Assemblage E was the dominating genotype and was distributed in three provinces. These assemblages of G. duodenalis have also been found in human beings, non-human primates, sheep, goats and cattle, which further reveals that farmed pigs pose a potential threat to public health.


A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.
The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.


Effect of storage temperature and time on fiber content of fresh and ensiled alfalfa.
To determine effects of storage temperature and time on fiber content, fresh alfalfa (late vegetative) was hand-clipped from three locations (blocks) and stored fresh or ensiled at -20 degrees C or +60 degrees C for 0, 24, 48, 96, 168, or 336 h. The experimental design was a randomized complete block with a 2 x 2 factorial arrangement of treatments. Main effects were method of forage conservation (fresh or ensiled) and temperature of storage (-20 degrees C or + 60 degrees C). Length of storage (0, 24, 48, 96, 168, or 336 h) was in the subplot. Conservation method x storage temperature x time interactions were detected (P < .05) for NDF, IVDMD, ADIN, and N content of NDF. Large increases in alfalfa NDF were observed up to 168 h of storage at 60 degrees C, whereas when fresh alfalfa was stored at -20 degrees C, small increases were observed up to 48 h but a large increase was observed after 168 h. Ensiled alfalfa stored at -20 degrees C had no change in NDF content. Contributors to increased NDF seemed due to changes in protein solubility and glycosylamine formation when fresh forage was stored at 60 degrees C, and changes in protein solubility, glycosylamine formation, and Maillard product formation when ensiled forage was stored at 60 degrees C. At -20 degrees C, formation of adducts with arabinose and glucose from nonstructural carbohydrates as well as polymerization and fragmentation of cell wall monosaccharides probably contributed to altered NDF content of alfalfa.


ACOG technology assessment. Genetics and molecular diagnostic testing. Number 1, July 2002. American College of Obstetrics and Gynecology.
Human genetics and molecular testing is playing an increasingly important role in obstetric and gynecologic practice. It is essential that obstetricians and gynecologists are aware of the advances in our understanding of genetic disease and the fundamental principles of molecular testing and genetic screening as genetics is integrated into routine medical practice. In the future, elucidation of the genetic basis for reproductive disorders, common diseases, and cancer with improved high throughput technology for genetic testing will expand testing opportunities and influence treatment options and prevention strategies.


The face behind the mask: a developmental study.
Faces are a rich and available source of social information, and the representation for faces is robust in adults (i.e. the face detection effect; Purcell & Stewart, 1988). The current study compared the developmental trajectory of the robustness of face perception against the trajectory for a non-face object. Participants (5-35 years old) were presented with rapid (17 and 33 millisecond) presentations of face and house stimuli and were instructed to identify the object category of the stimulus (face or house). There was an interaction between object type and age such that the developmental slope for face identification was steeper than the slope for house identification for the 17-millisecond presentation. These data show that faces are processed in a different way than a non-face object during the period from middle childhood through adolescence and adulthood, and this differential processing may involve the massive amount of exposure we have to faces.


Images in cardiology: left ventricular free wall rupture.
Left ventricular free wall rupture is thought to account for approximately 15% of deaths following acute myocardial infarction (MI). We present a case of left ventricular free wall rupture in a 64-year-old man following a lateral MI. The diagnosis was made with 2D and colour flow Doppler echocardiography. Unfortunately the patient died before emergency surgery could be performed.


Comparing Production and Efficacy of Cordyceps javanica With Cordyceps fumosorosea.
A newly discovered entomopathogenic fungus Cordyceps javanica (Friedrichs & Bally) Samson & Hywel-Jones (Hypocreales: Cordycipitaceae) strain Wf GA17 was compared with the commercial Cordyceps fumosorosea Wize (Hypocreales: Cordycipitaceae) Apopka 97 strain for liquid-culture production, formulation, insecticidal efficacy, and storage stability under laboratory conditions. We compared culture media with carbon:nitrogen (C:N) ratios of 10:1, 30:1, and 50:1 for these two isolates. A third strain, C. fumosorosea strain ARSEF 3581, had previously been optimized for liquid-culture production of blastospores at 10:1 C:N served as an added control. These seven cultures were processed by spray drying with skim milk powder, stored at 25oC to evaluate storage stability, and assayed for insecticidal activity against Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae) neonates. Final blastospore concentrations were not significantly different among cultures, ranging from 4.47 to 9.88 × 108 spores/ml. Fungal biomass decreased and final glucose concentrations increased with increasing C:N ratios, indicating better fungal growth with higher nitrogen concentrations. Product yields from the spray dryer (grams per liter culture) increased with increased C:N ratios while spore concentrations decreased, ranging from 2.27 to 7.17 × 109 spores/g. There were no significant differences for insecticidal efficacy among the seven treatments. Spores produced in 10:1 C:N ratio media retained viability longer than spores produced in other media. Cost of ingredients decreased with increasing C:N ratios, such that the 30:1 media may yield the most economical product. The raw material cost needed for application was 1.4× greater for Wf GA17 compared with Apopka 97, a difference that could be erased by optimization of culture conditions.


A surface of minimum area metric for the structural comparison of proteins.
A new method for comparing protein structures, based on a minimal surface metric, is developed. A virtual polypeptide backbone is created by joining consecutive C alpha atoms in a protein structure. The minimal surface between the virtual backbones of two proteins (the Area Functional) is determined numerically using an iterative triangulation strategy. The first protein is then rotated and translated in space until the smallest minimal surface is obtained. Such a technique yields the optimal structural superposition between two protein segments. It requires no initial sequence alignment, is relatively insensitive to insertions and deletions, and obviates the need to select a gap penalty. The optimal minimal area can then be converted to the Area-C alpha distance, measured in angstroms, to determine the structural similarity. This technique has been applied to a large class of proteins and is able to detect not only small-scale differences between closely related proteins but also large-scale topological similarities between evolutionary unrelated proteins that lack any obvious sequence homology. To measure the similarity between structurally dissimilar proteins, an additional measure (the Fit Comparison) is developed. This is a scale-invariant measure of a structural similarity that is useful for determining topological similarities between dissimilar proteins with unrelated sequences.


Photon-number fluctuation and correlation of bound soliton pairs in mode-locked fiber lasers.
Quantum photon-number fluctuation and correlation of bound soliton pairs in mode-locked fiber lasers are studied on the basis of the complex Ginzburg-Landau equation model. We find that, depending on their phase difference, the total photon-number noise of the bound soliton pair can be larger or smaller than that of a single soliton, and the two solitons in the soliton pair have a corresponding positive or negative photon-number correlation. It is predicted for the first time to our knowledge that out-of-phase soliton pairs can exhibit less noise as a result of negative correlation.


Emerging Progress in Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum: Challenges and Opportunities.
Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP, which is reported in 0.3-10.8% of pregnant women. NVP has a relatively benign course, but HG can be linked with some poor maternal, fetal, and offspring outcomes. The exact causes of NVP and HG are unknown, but various factors have been hypothesized to be associated with pathogenesis. With the advance of precision medicine and molecular biology, some genetic factors such as growth/differentiation factor 15 (GDF15) have become therapeutic targets. In our review, we summarize the historical hypotheses of the pathogenesis of NVP and HG including hormonal factors, Helicobacter pylori, gastrointestinal dysmotility, placenta-related factors, psychosocial factors, and new factors identified by genetics. We also highlight some approaches to the management of NVP and HG, including pharmacological treatment, complementary treatment, and some supporting treatments. Looking to the future, progress in understanding NVP and HG may reduce the adverse outcomes and improve the maternal quality of life during pregnancy.


Psychosomatic liaison service in medicine - need for psychotherapeutic interventions and their realisation.
The aim of the study was to evaluate the need for psychotherapeutic interventions and their realisation within the framework of the psychosomatic liaison service. Apart from establishing the diagnosis of psychosocial distress and mental disorders, we assessed the motivation of the patients for psychotherapy. 62 consecutive patients admitted to the Department of Medicine (Gastroenterology and Hepatology) Freiburg University Hospital, Freiburg, Germany, underwent standardised psychodiagnostic interviews and completed psychometric self-rating tests to identify mental disorders, psychosocial distress, and motivation for psychotherapy. In addition, the patients' need for psychotherapeutic treatment was rated by the liaison therapist. Using ICD 10-criteria, mental disorders were diagnosed in two thirds of the patients; most frequent were adjustment disorders, affective disorders, and disorders resulting from alcohol use. One third of the patients reported signs of psychological distress; half of them were interested in psychotherapy. A need for psychotherapeutic interventions, based on motivation of the patients and on expert estimate, was found in approximately one third of the patients. 36% received actual psychotherapy. Our study suggests that - in the patient population studied - the patients' motivation ought to be taken into consideration more strongly when evaluating the need for psychotherapy in clinical practice and further research.


Nitrite- and peroxide-dependent oxidation pathways of dopamine: 6-nitrodopamine and 6-hydroxydopamine formation as potential contributory mechanisms of oxidative stress- and nitric oxide-induced neurotoxicity in neuronal degeneration.
In the presence of nitrite ions (NO(2)(-)) in phosphate buffer (pH 7. 4) and at 37 degrees C, dopamine was oxidized by a variety of hydrogen peroxide (H(2)O(2))-dependent enzymatic and chemical systems to give, in addition to black melanin-like pigments via 5, 6-dihydroxyindoles, small amounts of the potent neurotoxin 6-hydroxydopamine (1) and of 6-nitrodopamine (2), a putative reaction product of dopamine with NO-derived species. Treatment of 0. 5 or 1 mM dopamine with horseradish peroxidase (HRP) or lactoperoxidase (LPO) in the presence of 1 or 2 mM H(2)O(2) with NO(2)(-) at a concentration of 0.5-10 mM resulted in the formation of 1 and 2 in up to 8 and 2 microM yields, respectively, depending on the substrate concentration and the NO(2)(-):H(2)O(2) ratio. Nitration and hydroxylation of 0.1 mM dopamine was observed with 1 mM NO(2)(-) using HRP and the D-glucose/glucose oxidase system to generate H(2)O(2) in situ. In the presence of NO(2)(-)-, Fe(2+)-, or Fe(2+)/EDTA-promoted oxidations of dopamine with H(2)O(2) also led to the formation of 1 and 2, the apparent product ratios varying with peroxide concentration and the partitioning of the metal between EDTA and catecholamine chelates. In the presence of NO(2)(-), Fe(2+)-promoted autoxidation of dopamine gave 2 but no detectable 1. When injected into the brains of laboratory rats, 2 caused sporadic behavioral changes, indicating that it could elicit a neurotoxic response, albeit to a lower extent than 1. Model experiments using tyrosinase as an oxidizing system and mechanistic considerations suggested that formation of 2 does not involve reactive nitrogen radicals but results mainly from nucleophilic attack of NO(2)(-) to dopamine quinone. Generation of 1, on the other hand, may be derives from different H(2)O(2)-dependent pathways. Collectively, these results outline a complex interplay of NO(2)(-)- and peroxide-dependent oxidation pathways of dopamine, which may contribute to impair dopaminergic neurotransmission and induce cytotoxic processes in neurodegenerative disorders.


Multi-institutional Collaboration to Promote Undergraduate Clinical Research Nursing.
Clinical research nursing is distinct from nursing research and includes the coordination and delivery of care for patients enrolled in clinical research trials. An innovative elective in clinical research nursing was developed collaboratively by stakeholders at a university, research institute, and national organization to provide experiential learning for undergraduate nursing students. The multi-institutional collaborative process, course overview, and precepted experience are described.


Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype.
A 'Down Syndrome critical region' (DSCR) sufficient to induce the most constant phenotypes of Down syndrome (DS) had been identified by studying partial (segmental) trisomy 21 (PT21) as an interval of 0.6-8.3 Mb within human chromosome 21 (Hsa21), although its existence was later questioned. We propose an innovative, systematic reanalysis of all described PT21 cases (from 1973 to 2015). In particular, we built an integrated, comparative map from 125 cases with or without DS fulfilling stringent cytogenetic and clinical criteria. The map allowed to define or exclude as candidates for DS fine Hsa21 sequence intervals, also integrating duplication copy number variants (CNVs) data. A highly restricted DSCR (HR-DSCR) of only 34 kb on distal 21q22.13 has been identified as the minimal region whose duplication is shared by all DS subjects and is absent in all non-DS subjects. Also being spared by any duplication CNV in healthy subjects, HR-DSCR is proposed as a candidate for the typical DS features, the intellectual disability and some facial phenotypes. HR-DSCR contains no known gene and has relevant homology only to the chimpanzee genome. Searching for HR-DSCR functional loci might become a priority for understanding the fundamental genotype-phenotype relationships in DS.


Properties of non-IPR fullerene films versus size of the building blocks.
This perspective focuses on the cage size dependent properties of novel solid fullerene nanofilms grown by soft-landing of mass-selected C(n)(+) (48, 50, 52, 54, 56, 58, 62, 64, 66 and 68) onto room temperature graphite surfaces under ultra-high vacuum conditions. Such non-isolated-pentagon-ring (non-IPR) fullerene materials are not accessible to standard fullerene preparation methods. The component molecular building blocks of non-IPR films were generated by electron impact induced ionization/fragmentation of sublimed IPR-C(70)(D(5h)) (-->C(n) (n = 68, 66, 64, 62)) or IPR-C(60)(I(h)) (-->C(n) (n = 58, 56, 54, 52, 50)). Non-IPR fullerene films on graphite grow via formation of dendritic C(n) aggregates, whereas deposition of IPR fullerenes under analogous conditions (via deposition of unfragmented C(60)(+) and C(70)(+)) leads to compact islands. The latter are governed by weak van der Waals cage-cage interactions. In contrast, the former are stabilized by covalent intercage bonds as mediated by the non-IPR sites (primarily adjacent pentagon pairs, AP). A significant fraction of the deposited non-IPR C(n) cages can be intactly (re)sublimed by heating. The corresponding mean desorption activation energies, E(des), increase from 2.1 eV for C(68) up to 2.6 eV for C(50). The densities of states in the valence band regions (DOS), surface ionization potentials (sIP) and HOMO-LUMO gaps (Delta) of semiconducting non-IPR films were measured and found to vary strongly with cage size. Overall, the n-dependencies of these properties can be interpreted in terms of covalently interconnected oligomeric structures comprising the most stable (neutral) C(n) isomers-as determined from density functional theory (DFT) calculations. Non-IPR fullerene films are the first known examples of elemental cluster materials in which the cluster building blocks are covalently but reversibly interconnected.


Tissue inhibitor of metalloproteinases (TIMP-1), genetic markers of insulin resistance and cardiomyopathy in patients with kidney failure.
Left ventricular hypertrophy (LVH) is a major cardiovascular (CV) complication in patients with kidney failure, and an association between polymorphisms in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, a genetic marker of insulin resistance, and LVH and Left ventricular (LV) concentric remodelling has been recently documented in these patients. Aims. Since myocardial fibrosis is a prominent feature in LVH induced by insulin resistance, we tested the hypothesis that the interaction between ENPP1 rs1974201 and rs9402349 polymorphisms and the tissue inhibitor of metalloproteinases (TIMP-1)--a pro-fibrotic protein which inhibits extracellular matrix degradation--is implicated in concentric LVH and diastolic dysfunction in a cohort of 223 dialysis patients. Both ENPP1 polymorphisms rs1974201 and rs9402349 were in Hardy-Weinberg equilibrium in dialysis patients. In an analysis stratified by ENPP1, rs1974201 polymorphism, circulating levels of TIMP-1 in GG patients were coherently associated with two markers of concentric remodelling [relative wall thickness (RWT) and LV mass-to-volume ratio] as well as with a marker of diastolic dysfunction (E/A ratio) (P ranging from 0.005 to 0.02), whereas no such associations existed in CC or CG patients. These observations suggest that the rs1974201 modifies the relationship between TIMP-1 and LV geometry and diastolic dysfunction. Accordingly, in a multiple regression model, an identical increase of TIMP-1 (100 ng/mL) was associated with an increase of 22% in RWT, 14% in LV mass-to-volume ratio and 29% in E/A ratio in GG patients but with almost no change (from -0.22 to -3.78%) in these echocardiographic indices in the remaining patients (P for the effect modification ≤ 0.024). The rs9402349 did not modify the relationship between TIMP-1 and LV geometry and function. In dialysis patients, the ENPP1 rs1974201 polymorphism modifies the association between TIMP-1 and LV geometry and diastolic function. These results are consistent with the hypothesis that insulin resistance is involved not only in LVH but also in myocardial fibrosis, an alteration of primary importance in the high risk of this population.


Calculating electron paramagnetic resonance g-matrices for triplet state molecules from multireference spin-orbit configuration interaction wave functions.
We present a way to calculate electron paramagnetic resonance (EPR) g-matrices from variationally optimized spin-orbit coupled wave functions. Our method constructs a triangular g-matrix from the matrix representation of the total electron magnetic moment in the basis of the spin-orbit coupled wave functions by means of a projection technique. Principal g-values are obtained in the standard fashion by forming from the triangular matrix g the tensor G=gg(t) and diagonalizing it. In principle, the scheme allows to calculate the spin-orbit orbital Zeeman cross term which usually gives the dominating contribution to the EPR g-shifts for any multiplicity. We have implemented this approach into a multireference spin-orbit configuration interaction (MRSOCI) program [M. Kleinschmidt et al., J. Chem. Phys. 124, 124101 (2006)]. Test applications are carried out for various triplet state sytems. The g-shifts of several of main group diatomics with X (3)Sigma(g)(-) ground state are investigated at the level of ab initio MRSOCI. We obtain perpendicular g-shifts which underestimate experimental Delta g(perpendicular) values from literature by approximately 13% on the average. For a set of organic triplet state molecules we employ the combined density functional theory/multireference configuration interaction (DFT/MRCI) technique [S. Grimme and M. Waletzke, J. Chem. Phys. 111, 5645 (1999)] to reduce the computational costs of the spin-free correlation problem. This approach yields principal g-values that match experiment well in many cases. Due to the small absolute g-shifts, a rigorous comparison will require the inclusion of first-order contributions such as the relativistic mass correction and gauge correction terms which have not been included here. For the triplet state dication trans-(CNSSS)(2)(2+) the principal g-shifts Delta g(a)=-0.3 ppt, Delta g(b)=17.5 ppt, and Delta g(c)=26.6 ppt are significantly larger and compare rather well to the experimental values Delta g(1)=-0.1+/-0.2 ppt, Delta g(2)=14.8+/-0.2 ppt, and Delta g(3)=24.8+/-0.1 ppt [A. Berces et al., Magn. Reson. Chem. 37, 353 (1999)]. In comparison to conventional truncated sum-over state techniques based on Rayleigh-Schrodinger perturbation theory, our new variational approach shows, in practice, robust and advantageous convergence characteristics with respect to the size of the many-particle basis set. We demonstrate that the DFT/MRSOCI technology is a very feasible means to compute reliable g-shifts for large organic triplet systems at low computational cost.


Dynamics of thyroid cancer incidence in Russia following the Chernobyl accident.
This paper presents an analysis of thyroid cancer incidence in the territories of Russia most contaminated after the Chernobyl accident. In the work, data on incidence in the Bryansk, Kaluga, Orel and Tula regions (5298000 persons) are used. Altogether, 2599 cases of thyroid cancer are considered from 1982 to 1995. Of them, 143 cases were among the population who were children and adolescents at the time of the accident in 1986. The work uses the approach based on comparison of distributions of thyroid cancer cases by age at diagnosis and age at exposure. It has been shown that since 1991 the age structure of the incidence has changed significantly with a growing proportion of cases among children and adolescents. The change in the structure occurred due to the radiation factor, specifically as a result of exposure of thyroid to incorporated 131I. It has been shown that the standardised incidence ratio (SIR) of thyroid cancer among children who were 0-4 years at exposure in 1991-6 was 6 to 10 times higher than among adults. On the average, SIR for children and adolescents at the time of exposure is about three times higher than in adults.


[Black dentifrice, white teeth?]
Activated charcoal-based whitening dentifrices claim to whiten teeth. Scientific evidence for the actual whitening effect, however, is still limited. A search in PubMed shows one randomized controlled double blinded in vitro study in which the'Black is White Curaprox® dentifrice is less effective in reducing extrinsic staining than other whitening dentifrices. One systematic literature review and one review article concluded there is insufficient scientific evidence to substantiate the cosmetic benefits of charcoal-based dentifrices.


In silico and NMR identification of inhibitors of the IGF-I and IGF-binding protein-5 interaction.
Recently we have determined the crystal structure of the insulin-like growth factor-I (IGF-I) in complex with the N-terminal domain of the IGF-binding protein-5 (IGFBP-5). Here we report results of computer screening for potential inhibitors of this interaction using the crystal coordinates. From the compounds suggested by in silico screens, successful binders were identified by NMR spectroscopic methods. NMR was also used to map their binding sites and calculate their binding affinities. Small molecular weight compounds (FMOC derivatives) bind to the IGF-I binding site on the IGFBP-5 with micromolar affinities and thus serve as potential starting compounds for the design of more potent inhibitors and therapeutic agents for diseases that are associated with abnormal IGF-I regulation.


Leg lengthening over an intramedullary nail.
Distraction osteogenesis is widely used for leg lengthening, but often requires a long period of external fixation which carries risks of pin-track sepsis, malalignment, stiffness of the joint and late fracture of the regenerate. We present the results of 20 cases in which, in an attempt to reduce the rate of complications, a combination of external fixation and intramedullary nailing was used. The mean gain in length was 4.7 cm (2 to 8.6). The mean time of external fixation was 20 days per centimetre gain in length. All distracted segments healed spontaneously without refracture or malalignment. There were three cases of deep infection, two of which occurred in patients who had had previous open fractures of the bone which was being lengthened. All resolved with appropriate treatment. This method allows early rehabilitation, with a rapid return of knee movement. There is a lower rate of complications than occurs when external fixation is used on its own. The time of external fixation is shorter than in other methods of leg lengthening. The high risk of infection calls for caution.


[Renal plasmacytoma].
Extramedullary plasmacytoma arising in the kidney is uncommon. So far only 11 cases have been reported. Recently, we noted the 12th case, the third case seen at the Kyoto University Hospital. The literature is reviewed. A 43-year-old man was hospitalized because of paraplegia due to spinal cord compression by the solitary plasmacytoma arising in the cervical spine, producing an IgG-lambda paraprotein. The tumor excision was followed by radiotherapy and standard chemotherapy. Two years later, new lesions on the thoracic spine, the left clavicle, and the occipital bone successively developed with Bence Jones proteinuria (lambda), but without IgG-lambda paraproteinemia. Ga-67 scanning was performed to detect extramedullary tumors. The marked accumulation of the radionuclide revealed intraabdominal tumors. A CT scan of the abdomen revealed a large soft-tissue mass (73 x 50 mm) emanating from the right kidney and several enlarged lymph nodes. Ultrasound of the right kidney revealed a solid mass with hydronephrotic change. RI-renogram showed delayed excretion from the right kidney. Clusters of myeloma cells were repeatedly observed in the urinary sediment. Thus, a diagnosis of plasmacytoma of the kidney was made. Treatment with radiotherapy alone was sufficient.


Coincidental hemochromatosis and viral hepatitis.
A 35-year-old woman presented with liver failure, hepatic iron overload, and secondary amenorrhea due to hypogonadotropic hypogonadism. She had chronic inflammatory hepatitis which was considered to be due to post-transfusional viral hepatitis. Her hepatic iron overload was considered to be due to hemochromatosis. Her premature menopause was thought to be due to the severity of her liver disease, but her iron overload also could have contributed to gonadotrophin deficiency. She underwent liver transplantation and 5 months later, she experienced return of menstrual function. The distinction between hepatitis as a cause of iron loading, hemochromatosis as a cause of hepatic inflammation, the small influence of alcohol on increased iron stores, and other features of her history, physical examination, and laboratory evaluation are discussed.


Heparin concentration in cell salvage during heparinization: a pilot study.
Cell salvage is frequently used to avoid unnecessary allogeneic blood transfusions, which results in a reduction in blood transfusion volume and cost. The aspirated blood is washed with normal saline and centrifuged to recover only blood cells, salvaged blood is then made. In cardiovascular surgery, heparin is used to maintain activated clotting time over 400 seconds. Some practitioners believe that heparin remains in the salvaged blood. Therefore, we hypothesized that salvaged blood during cardiovascular surgery includes heparin. A pilot study was conducted to evaluate our hypothesis using three different salvage systems. This study was a prospective, observational, pilot study, with patients aged 20-85 years old who were scheduled for cardiovascular surgery from May 2018 to October 2018. The intent of this study was to evaluate whether salvaged blood with three different devices includes large enough quantities of heparin to influence activated clotting time in cardiovascular surgery. Between May and October 2018, 12 samples during heparinization were collected, and 12 samples of salvaged blood from 3 devices were collected after administrating protamine. The heparin concentration of the 24 samples was measured. All heparin concentrations in salvage blood sample from two devices was below the limit of measurement (0.10 IU/mL). Slightly measurable heparin was detected in salvaged blood sample from one device (mean 0.15 IU/mL). Salvaged blood during cardiovascular surgery intervention does not contain enough heparin to influence activated clotting time.


Drug delivery system to control infectious diseases.
Viral replication takes place only in the host cell. From this intrinsic characteristics of virus, therapeutics agents specifically target to the virus genome is quite difficult. However, genetic medicine toward viral gene is promising in terms of selective toxicity for viral infection. Genetic medicine including antisense DNA, ribozyme, aptamer, triplex and gene itself has been enthusiastically studied in the past decades. At the early age of genetic medicine research, there were many skepticisms about clinicla usage. However, the first antisense DNA is on the market in the USA and Europe. Although the mechanism of antisense manner is still controversial, it was clearly epoch-making in the human application of genetic medicine. Genetic medicine opens the possibility to combat virus replication in a sequence specific way. Virus utilizes the specific receptor on the host cells for entry; this is the reason why virus has organ specificity (tropism). Since life cycle of each virus is unveiled, target for the therapeutic agent's reveals in a molecular level. Furthermore, decipher of viral genome has been carried out rapidly and inexpensively. Once we hand entire sequences of viral genome, more theoretical way to design genetic medicine targeted viral infection could be main stream in the development of antiviral agents. Furthermore, efficient drug delivery system (DDS) to deliver antiviral agents to the infectious site is highly needed. In this article, we will address the target molecule of antiviral agents and possible DDS for the infectious disease.


Intraoral lesion · history of cirrhosis and smoking · Dx?
A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate. The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient's medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.


Cytotoxic Cardiac Glycoside Constituents of Vallaris glabra Leaves.
Thirteen cardenolide glycosides (1-13) were isolated from the CH2Cl2 and MeOH extracts of Vallaris glabra leaves. The structures of the new compounds (2-13) were identified by spectroscopic methods, with the absolute configurations of the sugar moieties determined by acid hydrolysis. All compounds were evaluated for their cytotoxic activity against human cervix adenocarcinoma, lung carcinoma, and colorectal adenocarcinoma cell lines. The two most potent compounds [2'-O-acetylacoschimperoside P (1) and oleandrigenin-3-O-α-l-2'-O-acetylvallaropyranoside (2)] exhibited IC50 values in the range of 0.03-0.07 μM.


Characterization of a B-lymphocyte t(2;14) (p11;q32) translocation from an ataxia telangiectasia patient conferring a proliferative advantage on cells in vitro.
Patients with the recessively inherited disorder ataxia telangiectasia (AT) are particularly prone to the development of both B-cell and T-cell tumours. Specific translocations involving T-cell gene rearrangements and an unknown locus 3' of IGH have been described in AT T-cell clone and tumour cells. We describe here a t(2;14)(p11;q32) translocation which was observed in nonmalignant short-term-cultured B lymphocytes from an AT patient. In vivo, the clone of cells grew from 1% to 6% of the total cell population over a period of 2 yr. Clonal translocations may therefore be associated with AT B cells, as well as AT T cells. B lymphocytes were transformed with Epstein-Barr virus, and the t(2;14) translocation cell was cellularly cloned. Using Southern filter analysis and in situ hybridisation to define more clearly the positions of the breakpoints, we show that the translocation at 14q32 involves a deletion within the IGH chain gene of at least J1, J2, DQ52, and sequences 1.5 kb 5' of DQ52 and that the breakpoint is either adjacent to the non-deleted JH sequences or upstream of these sequences, within the D or V regions, but proximal to all members of the VHII family of genes. The breakpoint at 2p11 is outside and proximal to IGK with respect to the centromere in an unknown gene. Sub-lines with an initially low proportion of translocation cells eventually became monoclonal in vitro for these cells. This suggests they have a growth advantage in vitro.


Immunotherapy of respiratory syncytial virus pneumonia following bone marrow transplantation.
Respiratory syncytial virus (RSV) pneumonia is a well-recognized complication of bone marrow transplantation with a high mortality rate. We describe two patients who developed RSV pneumonia within the first 3 weeks following allogeneic bone marrow transplantation. These patients had significant oxygen requirements and radiographic infiltrates. Both were treated with aerosolized ribavirin and given a single 1.5 gm/kg dose of intravenous immune globulin containing high levels of RSV neutralizing activity (RSV-IG). Both patients showed subjective and objective improvement after RSV-IG, never required mechanical ventilation, and were discharged without an oxygen requirement within 2 weeks after therapy. RSV microneutralization activity was measured in serum and nasal secretions. Mean serum microneutralization activity increased from 2279 microneutralization units (Mu)/ml to 18082 Mu/ml after RSV-IG. Peak serum microneutralization activity achieved with RSV-IG was higher than that achieved in a series of other immunocompromised adults with RSV pneumonia given either multiple doses of standard IVIG or no immune globulin therapy. RSV-IG may be beneficial in the treatment of RSV pneumonia in severely immunocompromised patients.


The chromosome partitioning proteins Soj (ParA) and Spo0J (ParB) contribute to accurate chromosome partitioning, separation of replicated sister origins, and regulation of replication initiation in Bacillus subtilis.
Soj (ParA) and Spo0J (ParB) of Bacillus subtilis belong to a conserved family of proteins required for efficient plasmid and chromosome partitioning in many bacterial species. Unlike most Par systems, for which intact copies of both parA and parB are required for the Par system to function, inactivating soj does not cause a detectable chromosome partitioning phenotype whereas inactivating spo0J leads to a 100-fold increase in the production of anucleate cells. This suggested either that Soj does not function like other ParA homologues, or that a cellular factor might compensate for the absence of soj. We found that inactivating smc, the gene encoding the structural maintenance of chromosomes (SMC) protein, unmasked a role for Soj in chromosome partitioning. A soj null mutation dramatically enhanced production of anucleate cells in an smc null mutant. To look for effects of a soj null on other phenotypes perturbed in a spo0J null mutant, we analysed replication initiation and origin positioning in (soj-spo0J)+, Deltasoj, Deltaspo0J and Delta(soj-spo0J) cells. All of the mutations caused increased initiation of replication and, to varying extents, affected origin positioning. Using a new assay to measure separation of the chromosomal origins, we found that inactivating soj, spo0J or both led to a significant defect in separating replicated sister origins, such that the origins remain too close to be spatially resolved. Separation of a region outside the origin was not affected. These results indicate that there are probably factors helping to pair sister origin regions for part of the replication cycle, and that Soj and Spo0J may antagonize this pairing to contribute to timely separation of replicated origins. The effects of Deltasoj, Deltaspo0J and Delta(soj-spo0J) mutations on origin positioning, chromosome partitioning and replication initiation may be a secondary consequence of a defect in separating replicated origins.


Antithrombotic drugs and non-variceal bleeding outcomes and risk scoring systems: comparison of Glasgow Blatchford, Rockall and Charlson scores.
Antithrombotic drugs (ATDs) cause non-variceal upper gastrointestinal bleeding (NVUGIB). Risk scoring systems have not been validated in ATD users. We compared Blatchford, Rockall and Charlson scores in predicting outcomes of NVUGIB in ATD users and controls. A total of 2071 patients with NVUGIB were grouped into ATD users (n=851) and controls (n=1220) in a single-centre retrospective analysis. Outcomes included duration of hospital admission, the need for blood transfusion, rebleeding requiring surgery and 30-day mortality. Duration of admission correlated with all scores in controls, but correlations were significantly weaker in ATD users. Rank correlation coefficients in control versus ATD: 0.45 vs 0.20 for Blatchford; 0.48 vs 0.32 for Rockall and 0.42 vs 0.26 for Charlson (all p<0.001). The need for transfusion was best predicted by Blatchford (p<0.001 vs Rockall and Charlson in both ATD users and controls), but all scores performed less well in ATD users. Area under the receiver operation characteristic curve (AUC) in control versus ATD: 0.90 vs 0.85 for Blatchford; 0.77 vs 0.61 for Rockall and 0.69 vs 0.56 for Charlson (all p<0.005). In predicting surgery, Rockall performed best; while mortality was best predicted by Charlson with lower AUCs in ATD patients than controls (p<0.05). Stratification showed the scores' performance to be age-dependent. Blatchford score was the strongest predictor of transfusion, Rockall's had the strongest correlation with duration of admission and with rebleeding requiring surgery and Charlson was best in predicting 30-day mortality. Modifications of these systems should be explored to improve their efficiency in ATD users.


Preliminary measurements of x-ray and neutron emission from laser-produced plasmas.
Two Nd-glass laser systems have been assembled for producing high-temperature plasmas. The smaller laser, which gives subnanosecond pulses of about 5 J, has been used primarily for x-ray studies. The spectrum above 2 keV is being explored using Bragg reflection from a cylindrically curved graphite crystal. Line radiation appears to be present in the spectra measured for laser-produced plasmas of lead and gold. Plasma temperatures implied by x-ray transmission measurements are found to vary with absorber thickness. Temperatures of a few tens of keV, inferred from thick-absorber measurements of low-Z plasmas, suggest the operation of anomalous heating mechanisms. A second glass laser system, involving face-pumped disks 14 cm in diameter, is also in use for plasma-heating experiments and has led to the production of D-D neutrons. This system has been used to produce pulses of several tens of joules in a few nanoseconds for recent experiments. A calibrated plastic scintillator with two photomultipliers is used f r neutron detection. Targets of CD(2) have produced total yields of more than 10(4) neutrons. Effective neutron production appears to require laser pulses longer than 2 nsec and to be accompanied by a large reflected pulse.


Identification of novel homozygous missense and deletion mutations manifesting oligospermia infertility in Kashmiri population.
Human male infertility has a lot of known molecular components that have an accurate diagnosis, such as Y chromosome deletion and monogenic causes. Only 4% of all infertile males are diagnosed with genetic causes, while 60-70% of infertile men remain without an accurate diagnosis and are classified as unexplained. Oligospermia is a major cause of human male infertility. Its etiology and pathogenesis are linked to genetic abnormalities. The majority of genetic causes related to human male infertility remain unclear. Generally, we found a significant association between the specific type of disease and gender (p = 0.003), and the regression value (R2 ) for this association was 0.75. Association of the type of disease with body mass index was not significant (p = 0.34). There was no statistically significant difference (p = 0.40) among disease types with patients occupations. All explored mutations are listed for primary and secondary infertility in relation to the oligospermia condition. p.Arg286X is the outcome of a mismatch mutation in which the nucleotide change resulted in the substitution of Arg (arginine) amino acid with X (any amino acid) at position 286 in the Hyal3 gene of primary infertile patients having oligospermia. In primary infertile patients with the p.Arg286X mutation, a frameshift deletion mutation was also found just after the 25 nucleotide sequences of the Hyal3 genes of the second mutated exon. This deletion mutation was only detected in patients with primary infertility and was not found in people with secondary infertility or healthy controls. The other mutations in secondary infertile patients with oligospermia were: p.Lys168Ser, replacement of lysine (Lys) with serine (Ser) at position 168; p.Lys168The, replacement of lysine (Lys) with threonine (The) at position 168; p.His113X, substitution of histidine (His) with an unknown amino acid (X) at position 113; p.Pro162X, substitution of proline (Pro) with an unknown amino acid (X) at position 162; and p.Phe157X, phenylalanine (Phe) substitution with an unknown amino acid (X) at position 157. This study clarifies the site of novel mismatch and frameshift deletion mutations in the Hyal3 gene in primary infertile oligospermia patients.


Fatal vascular access hemorrhage: reducing the odds.
Vascular access hemorrhage is not a frequently occurring complication associated with hemodialysis fistulas and grafts, but when it occurs, it can be fatal to patients and devastating to patients' families and dialysis unit staff members. The End Stage Renal Disease Notification of Death CMS-2746 forms indicated that between the years 2000 and 2006 (the most recent national data available), there were 1654 fatal vascular access hemorrhages. Specific issues that place patients at high risk for access rupture have been identified, and some are directly related to access physical assessment and cannulation. Recognizing at-risk accesses during physical assessment and improving site selection for needle placement can modify some risk factors for fatal vascular access hemorrhage and improve patient outcomes.


Shedding Light on Cast Shadows: An Investigation of Perceived Ground Contact in AR and VR.
Virtual objects in augmented reality (AR) often appear to float atop real world surfaces, which makes it difficult to determine where they are positioned in space. This is problematic as many applications for AR require accurate spatial perception. In the current study, we examine how the way we render cast shadows-which act as an important monocular depth cue for creating a sense of contact between an object and the surface beneath it-impacts spatial perception. Over two experiments, we evaluate people's sense of surface contact given both traditional and non-traditional shadow shading methods in optical see-through augmented reality (OST AR), video see-through augmented reality (VST AR), and virtual reality (VR) head-mounted displays. Our results provide evidence that nontraditional shading techniques for rendering shadows in AR displays may enhance the accuracy of one's perception of surface contact. This finding implies a possible tradeoff between photorealism and accuracy of depth perception, especially in OST AR displays. However, it also supports the use of more stylized graphics like non-traditional cast shadows to improve perception and interaction in AR applications.


Deciphering modes of long-range energy transfer in perovskite crystals using confocal excitation and wide-field fluorescence spectral imaging.
Excitation energy migration beyond mesoscale is of contemporary interest for both solar photovoltaic and light-emissive devices, especially in context of organometal halide perovskites (OMHPs) which have been shown to have very long (charge carrier) diffusion lengths. While understanding the energy propagation pathways in OMHPs is crucial for further advancement of material design and improvement of opto-electronic features, the simultaneous existence of multiple processes like carrier diffusion, photon recycling, and photon transport makes it often complex to differentiate them. In this study, we unravel the diverse yet dominant excitation energy transfer mode(s) in crystalline MAPbBr3micron-sized 1D rods and plates by localized (confocal) laser excitation coupled with spectrally-resolved wide-field fluorescence imaging. While rarely used, this technique can efficiently probe excitation migration beyond the diffraction limit and can be realized by simple modification of existing epifluorescence microscopy setups. We find that in rods of length below ∼2 microns, carrier diffusion dominates amongst various energy transfer processes. However, the transient non-radiative defects severely inhibit the extent of carrier migration and also temporarily affect the radiative recombination dynamics of the photo-carriers. For MAPbBr3plates of several tens of micrometers, we find that the photoluminescence (PL) spectral characteristics remain unaltered at short distances (< ∼3μm) while at a larger distance, the spectral profile is gradually red-shifted. This implies that carrier diffusion dominates over small distances, while photon recycling,i.e., repeated re-absorption and re-emission of photons, propagates excitation energy transfer over extended length scales with assistance from wave-guided photon transport. Our findings can potentially be used for future studies on the characterization of energy transport mechanisms in semiconductor solids as well as for organic (molecular) self-assembled microstructures.


Game-Related Statistics that Discriminated Winning, Drawing and Losing Teams from the Spanish Soccer League.
The aim of the present study was to analyze men's football competitions, trying to identify which game-related statistics allow to discriminate winning, drawing and losing teams. The sample used corresponded to 380 games from the 2008-2009 season of the Spanish Men's Professional League. The game-related statistics gathered were: total shots, shots on goal, effectiveness, assists, crosses, offsides commited and received, corners, ball possession, crosses against, fouls committed and received, corners against, yellow and red cards, and venue. An univariate (t-test) and multivariate (discriminant) analysis of data was done. The results showed that winning teams had averages that were significantly higher for the following game statistics: total shots (p < 0.001), shots on goal (p < 0.01), effectiveness (p < 0.01), assists (p < 0.01), offsides committed (p < 0.01) and crosses against (p < 0.01). Losing teams had significantly higher averages in the variable crosses (p < 0.01), offsides received (p < 0. 01) and red cards (p < 0.01). Discriminant analysis allowed to conclude the following: the variables that discriminate between winning, drawing and losing teams were the total shots, shots on goal, crosses, crosses against, ball possession and venue. Coaches and players should be aware for these different profiles in order to increase knowledge about game cognitive and motor solicitation and, therefore, to evaluate specificity at the time of practice and game planning. Key pointsThis paper increases the knowledge about soccer match analysis.Give normative values to establish practice and match objectives.Give applications ideas to connect research with coaches' practice.