Pediatric integrative medicine: pediatrics' newest subspecialty?
Integrative medicine is defined as relationship-centered care that focuses on the whole person, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing, including evidence-based complementary and alternative medicine. Pediatric integrative medicine (PIM) develops and promotes this approach within the field of pediatrics. We conducted a survey to identify and describe PIM programs within academic children's hospitals across North America. Key barriers and opportunities were identified for the growth and development of academic PIM initiatives in the US and Canada. Academic PIM programs were identified by email and eligible for inclusion if they had each of educational, clinical, and research activities. Program directors were interviewed by telephone regarding their clinical, research, educational, and operational aspects. Sixteen programs were included. Most (75%) programs provided both inpatient and outpatient services. Seven programs operated with less than 1 FTE clinical personnel. Credentialing of complementary and alternative medicine (CAM) providers varied substantially across the programs and between inpatient and outpatient services. Almost all (94%) programs offered educational opportunities for residents in pediatrics and/or family medicine. One fifth (20%) of the educational programs were mandatory for medical students. Research was conducted in a range of topics, but half of the programs reported lack of research funding and/or time. Thirty-one percent of the programs relied on fee-for-service income. Pediatric integrative medicine is emerging as a new subspecialty to better help address 21st century patient concerns.


Specificity of emotion regulation deficits in social anxiety: an internet study.
There is evidence for an association between social anxiety and emotion regulation difficulties. This study investigates that emotion regulation difficulties are specific to two domains of social anxiety. An explorative study was conducted to examine the associations between emotion regulation facets and social anxiety in the normal population. N= 149 healthy volunteers participated in an internet-based survey. Emotion regulation deficits were measured by the Difficulties in Emotion Regulation Scale which consists of six subscales. Social anxiety was measured by the Social Phobia Scale and the Social Interaction Anxiety Scale. Hierarchical regression analyses showed that anxiety of interactive social situations is associated with non-acceptance of negative emotions, impulse control difficulties, and lack of functional emotion regulation strategies over and above the impact of age and general psychopathology. In contrast, anxiety of being observed by others was not specifically associated with emotion regulation strategies. The results support the hypothesis that specific emotion regulation deficits are relevant to specific aspects of social anxiety. Implications for further research and therapy are discussed.


Development of an in vitro potency assay for anti-anthrax lethal toxin neutralizing antibodies.
Lethal toxin (LT) of Bacillus anthracis reduces the production of a number of inflammatory mediators, including transcription factors, chemokines and cytokines in various human cell lines, leading to down-regulation of the host inflammatory response. Previously we showed that the reduction of interleukin-8 (IL-8) is a sensitive marker of LT-mediated intoxication in human neutrophil-like NB-4 cells and that IL-8 levels are restored to normality when therapeutic monoclonal antibodies (mAb) with toxin-neutralising (TN) activity are added. We used this information to develop cell-based assays that examine the effects of TN therapeutic mAbs designed to treat LT intoxication and here we extend these findings. We present an in vitro assay based on human endothelial cell line HUVEC jr2, which measures the TN activity of therapeutic anti-LT mAbs using IL-8 as a marker for intoxication. HUVEC jr2 cells have the advantage over NB-4 cells that they are adherent, do not require a differentiation step and can be used in a microtitre plate format and therefore can facilitate high throughput analysis. This human cell-based assay provides a valid alternative to the mouse macrophage assay as it is a more biologically relevant model of the effects of toxin-neutralising antibodies in human infection.


Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors.
A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m(2)) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O(6)-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n=23) and compared with response to temozolomide. Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O(6)-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.


[Conflict of interest disclosure as a tool to improve the reliability of research].
Conflicts of interest are situations in which professional judgment concerning a primary interest, tends to be influenced by a secondary interest. These conflicts could compromise the reliability of biomedical research and result in the dissemination of biased results. Therefore, it is essential to protect the integrity of them, because this information could be used in the development of health policy, medical education and clinical decision making. Conflicts of interest disclosure, is a bioethical tool that contributes to transparent these conflicts, but it is used inappropriately and insufficiently. To be useful, it must be based on clear principles, it should help to perform a critical analysis and should be considered in the design of every research project. This review is an analysis of the conflicts of interest disclosure, its scope and limitations and should contribute to develop a greater awareness of its importance.


Functional properties and connective tissue content of pediatric human detrusor muscle.
The functional properties of human pediatric detrusor smooth muscle are poorly described, in contrast to those of adult tissue. Characterization is necessary for more informed management options of bladder dysfunction in children. We therefore compared the histological, contractile, intracellular Ca2+ concentration responses and biomechanical properties of detrusor biopsy samples from pediatric (3-48 mo) and adults (40-60 yr) patients who had functionally normal bladders and were undergoing open surgery. The smooth muscle fraction of biopsies was isolated to measure proportions of smooth muscle and connective tissue (van Gieson stain); in muscle strips, isometric tension to contractile agonists or electrical field stimulation and their passive biomechanical properties; in isolated myocytes, intracellular Ca2+ concentration responses to agonists. Pediatric detrusor tissue compared with adult tissue showed several differences: a smaller smooth muscle-to-connective tissue ratio, similar contractures to carbachol or α,β-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+ transients to carbachol, α,β-methylene ATP, raised K+ concentration or caffeine, but smaller nerve-mediated contractions and greater passive stiffness with slower stress relaxation. In particular, there were significant atropine-resistant nerve-mediated contractions in pediatric samples. Detrusor smooth muscle from functionally normal pediatric human bladders is less contractile than that from adult bladders and exhibits greater passive stiffness. Reduced bladder contractile function is not due to reduced smooth muscle contractility but to greater connective tissue deposition and to functional denervation. Significant atropine resistance in pediatric detrusor, unlike in adult tissue, demonstrates a different profile of functional neurotransmitter activation. These data have implications for the management of pediatric bladder function by therapeutic approaches.


Downregulation of uPARAP mediates cytoskeletal rearrangements and decreases invasion and migration properties in glioma cells.
To identify molecular therapeutic targets for glioma, we performed gene expression profiling by using a complementary DNA (cDNA) microarray method and identified the urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180) as a gene expressed highly in glioma tissue compared with the normal brain tissue. The uPARAP is an endocytic receptor for collagen. In certain cell types, uPARAP occurs in a complex with the urokinase plasminogen activator receptor (uPAR) where it fulfills other functions in addition to collagenolysis. Quantitative PCR analysis using a cDNA panel revealed higher expression levels of uPARAP in glioma tissue compared with normal brain tissue. Western blot analysis revealed that the uPARAP protein was expressed in glioma samples and two glioma cell lines, KNS42 and KNS81, but not expressed in control tissue from the normal brain. Introduction of small interfering RNA-targeted uPARAP into the two different glioma cell lines, KNS42 and KNS81, resulted in downregulation of uPARAP expression, and it significantly suppressed glioma cell migration and invasion in vitro. Control glioma cells showed small cell bodies, whereas uPARAP siRNA-treated glioma cells exhibited large and flat morphology. Most of the polymeric actin in the control glioma cells was concentrated in the lamellipodia that are observed in mobile cells. In contrast, in the uPARAP siRNA-treated glioma cells, polymeric actin became organized in stress fibers and the lamellipodia disappeared, characteristic of immobile cells. Our present study suggests that uPARAP may be involved in glioma cell invasiveness through actin cytoskeletal rearrangement. downregulation of uPARAP may be a novel anti-invasion therapeutic strategy for malignant gliomas.


Mechanisms of functional and physical genome reduction in photosynthetic and nonphotosynthetic parasitic plants of the broomrape family.
Nonphotosynthetic plants possess strongly reconfigured plastomes attributable to convergent losses of photosynthesis and housekeeping genes, making them excellent systems for studying genome evolution under relaxed selective pressures. We report the complete plastomes of 10 photosynthetic and nonphotosynthetic parasites plus their nonparasitic sister from the broomrape family (Orobanchaceae). By reconstructing the history of gene losses and genome reconfigurations, we find that the establishment of obligate parasitism triggers the relaxation of selective constraints. Partly because of independent losses of one inverted repeat region, Orobanchaceae plastomes vary 3.5-fold in size, with 45 kb in American squawroot (Conopholis americana) representing the smallest plastome reported from land plants. Of the 42 to 74 retained unique genes, only 16 protein genes, 15 tRNAs, and four rRNAs are commonly found. Several holoparasites retain ATP synthase genes with intact open reading frames, suggesting a prolonged function in these plants. The loss of photosynthesis alters the chromosomal architecture in that recombinogenic factors accumulate, fostering large-scale chromosomal rearrangements as functional reduction proceeds. The retention of DNA fragments is strongly influenced by both their proximity to genes under selection and the co-occurrence with those in operons, indicating complex constraints beyond gene function that determine the evolutionary survival time of plastid regions in nonphotosynthetic plants.


Although inconvenient, baclofen pumps do not complicate scoliosis surgery in patients with cerebral palsy.
Retrospective review of prospectively collected data. To compare patients with operative cerebral palsy with and without an intrathecal baclofen pump (ITB) to determine whether an ITB increases the complexity of scoliosis surgery and/or increases the risk of wound complications. Options for baclofen pump placement include before, during, or after scoliosis surgery. There is some concern that prior placement of an ITB and catheter can further complicate cerebral palsy scoliosis surgery and increase the risk for wound complications. Prospectively collected cases from a multicenter cerebral palsy scoliosis database were reviewed for patients who underwent posterior spinal instrumentation and fusion for a major coronal deformity. These patients were then divided on the basis of whether they had ITB at the time of initial scoliosis surgery. The 2 groups were compared to determine differences in demographics, operative parameters, radiographical outcomes, and rates of wound complications. Of 187 patients identified, 32 had an ITB previously placed (ITB group) and 155 did not (non-ITB group). Both groups were similar in regard to age, sex, Gross Motor Function Classification Scale score, and preoperative Cobb magnitude. When comparing operative parameters, there were no differences in the total operating room time (ITB = 375 ± 127 min, non-ITB = 423 ± 178 min; P = 0.149) or total estimated blood loss (ITB = 2323 ± 1489 mL, non-ITB = 2081 ± 1572 mL; P = 0.424). Postoperatively, the 2 groups had similar correction rates (71% vs. 67%, P = 0.303). As for perioperative wound complications, there were no differences in rates (P = 0.546) between the ITB (16%) and non-ITB group (15%). Although it may be inconvenient for the surgeon, ITBs do not increase the complexity of surgery or the risk for wound complications. When counseling patients and their caregivers on the timing of pump placement, it does not seem to compromise the care of the patient if the baclofen pump is placed first. Further study is needed to evaluate the safety of pump placement during or after scoliosis surgery. 4.


Isolation and characterization of Streptococcus mutans mutants with altered cellular morphology or chain length.
A nitrosoguanidine-induced mutant, designated UAB90, of Streptococcus mutans PS14 (serotype c) strain UAB62, was identified on the basis of its unique colony morphology and isolated on brain heart infusion agar. Other mutants displaying similar colony morphologies on brain heart infusion agar were isolated after ethyl methane sulfonate mutagenesis of UAB62 and S. mutans 6715 (serotype g) strains UAB61 and UAB66, and these were found to exhibit abnormalities in cell morphology, chain length, or both. All mutants were examined further for (i) adherence and aggregation after overnight growth in medium containing sucrose, (ii) growth and aggregation in brain heart infusion broth and medium containing glucose, (iii) aggregation of nongrowing cells in the presence of 2 mg of sucrose per ml or 200 mug of dextran per ml, (iv) dextranase activity, and (v) ease of cell lysis. Mutants isolated included several with long chains of enlarged cocci, and two of these strains, UAB261 and UAB433, along with UAB90, were more susceptible to cell lysis than were their parents. UAB261, isolated from UAB62, maintained other parental characteristics, whereas UAB433, isolated from UAB66, lost its ability to aggregate in the presence of either sucrose or dextran. The "fragile" mutant UAB90 was particularly useful in the isolation of high-molecular-weight DNA for early gene cloning experiments by our laboratory. Two other cell morphology mutants, UAB272 from UAB66 and UAB289 from UAB61, did not lyse better than their parents, but both lacked measurable dextranase activity. A final mutant, UAB276 from UAB66, displayed only increased chain length without apparent cell morphology variations. Chains produced by this mutant were up to 10 times longer than those produced by UAB66. UAB276 lysed slightly less well than its parent but retained all other wild-type characteristics examined.


Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children.
Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.


Species and cultural conservation in New Zealand: maori traditional ecological knowledge of tuatara.
Traditional ecological knowledge can be highly informative and integrated with complementary scientific knowledge to improve species management. This is especially true for abundant species with which indigenous peoples have frequent interactions (e.g., through harvest), but has been studied less frequently in isolated or declining species. We examined Maori traditional ecological knowledge of tuatara (Sphenodon spp., reptiles that resemble lizards but are the last living representatives of the order Sphenodontia) through semidirected interviews of elders of Te Atiawa, Ngati Koata, and Ngati Wai Iwi (similar to tribes), the guardians of several islands currently inhabited by tuatara. Maori are indigenous to New Zealand, having settled 800 to 1000 years ago. Tuatara are endemic to New Zealand, have declined in numbers since human settlement, and are now restricted to 37 offshore islands. The detail and volume of tuatara traditional ecological knowledge were less than that recorded in studies of more abundant or accessible species. In addition, traditional knowledge of the cultural significance of tuatara was more common and detailed among the elders than traditional knowledge of tuatara biology or ecology. The traditional knowledge collected, however, provided the first evidence of seven former sites of tuatara occupation, suggested five additional sites tuatara may currently occupy, contained novel hypotheses for scientific testing, and described tuatara cultural roles that have not been reported previously. We conclude that, in at least some cases, traditional ecological knowledge may persist as species decline and may serve as a valuable source of ecological information for conservation.


5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders.
Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD.


Stress and parenting predict changes in adolescent respiratory sinus arrhythmia.
Adolescence is a critical period for the development of physiological emotion regulatory systems. While stressful life experiences are known to inhibit adaptive regulation, less is known about how parental socialization of emotion regulation may affect this relation. We examined the effect of stressful life experiences on changes in the resting respiratory sinus arrhythmia (RSA) levels of 107 (Mage = 12.84, SD = 0.85) young adolescents over a year, moderated by supportive parental responses to negative emotions. The significant interaction (B = 0.02, p = 0.04) indicated that young adolescents who experienced low levels of supportive parenting in the context of high levels of stressful life experiences showed significant decreases in resting RSA over the year, while adolescents who experienced high levels of supportive parenting showed minimal decreases in RSA. Thus, more supportive parenting significantly compensated for the effect of greater stressful life experiences on changes in resting RSA over time.


Idiopathic Subjective Tinnitus Treated by Amitriptyline Hydrochloride/Biofeedback.
The efficiency of two treatment modalities for subjective/idiopathic tinnitus (SIT): biofeedback (BF) and amitriptyline hydrochloride (AT) was investigated in 225 randomly selected subjects. Findings show that after 10 weeks of treatment in the BF group, 43.5% of the patients reported an improvement of tinnitus during activity. In the AT group, 27.5% of patients reported subjective improvement of tinnitus at rest although only 15.8% of the AT patients reported improvement during activity. Biofeedback during rest had a significantly better effect on tinnitus disturbance than AT. No objective diminishment of tinnitus loudness was found as a result of any of the treatment modalities. We believe that BF can help tinnitus patients especially during periods of rest and we also suggest trying tricyclic antidepressant drugs such as AT for treatment of tinnitus patients, in small doses, however, to minimize the side effects of this drug. Subjective tinnitus (ST) is one of the most common and yet most unclear of otologic symptoms.(1-4) ST can accompany any type of hearing loss including both sensorineural as well as conductive hearing loss, and may originate from any part of the auditory pathway.(1,5) Treatment of ST must be primarily directed to the basic illness diagnosed after a thorough general ear-nose-throat and neurologic evaluation.(6) Severity of ST is evaluated both objectively, by determining the pitch and intensity of the tinnitus,(7) and subjectively as described by the patient. Because of the relatively high incidence of ST and in some patients, the severe personal reaction to it, many different treatments have been suggested, but generally only small to moderate success has been achieved in reducing tinnitus and its consequences, if any at all.(8) In this study we examined the effect of two treatment modalities: amitriptyline hydro-chloride and biofeedback.


[Cardiovascular autonomic regulation following orthoptic heart transplantation].
Numerous recent observations have indicated autonomic reinnervation of transplanted human hearts. In order to assess autonomic regulation 5 patients were studied 1 to 5 years following cardiac transplantation. A series of tests were performed, including blood pressure and ECG recordings on rest, during 15/min patterned breathing, isometric handgrip exercise, and Valsalva manoeuvre. The time domain indices (SDRR, pNN50, rMSSD) and the frequency domain indices of heart rate variability were also studied. Among the five patients under study only one exhibited features compatible with both sympathetic and parasympathetic reinnervation. Traditional autonomic reflex tests and the analysis of time and frequency domain indices of HRV serve as simple tool in primary assessment of cardiac reinnervation.


Hydrogen production by the engineered cyanobacterial strain Nostoc PCC 7120 ΔhupW examined in a flat panel photobioreactor system.
Nitrogenase based hydrogen production was examined in a ΔhupW strain of the filamentous heterocystous cyanobacterium Nostoc PCC 7120, i.e., cells lacking the last step in the maturation system of the large subunit of the uptake hydrogenase and as a consequence with a non-functional uptake hydrogenase. The cells were grown in a developed flat panel photobioreactor system with 3.0L culture volume either aerobically (air) or anaerobically (Ar or 80% N2/20% Ar) and illuminated with a mixture of red and white LED. Aerobic growth of the ΔhupW strain of Nostoc PCC 7120 at 44μmolar photons m(-2)s(-1) PAR gave the highest hydrogen production of 0.7mL H2 L(-1)h(-1), 0.53mmol H2 mg chlorophyll a(-1)h(-1), and a light energy conversion efficiency of 1.2%. Anaerobic growth using 100% argon showed a maximal hydrogen production of 1.7mLL(-1)h(-1), 0.85mmol per mg chlorophyll a(-1) h(-1), and a light energy conversion efficiency of 2.7%. Altering between argon/N2 (20/80) and 100% argon phases resulted in a maximal hydrogen production at hour 128 (100% argon phase) with 6.2mL H2L(-1)h(-1), 0.71mL H2 mg chlorophyll a(-1)h(-1), and a light energy efficiency conversion of 4.0%. The highest buildup of hydrogen gas observed was 6.89% H2 (100% argon phase) of the total photobioreactor system with a maximal production of 4.85mL H2 L(-1)h(-1). The present study clearly demonstrates the potential to use purpose design cyanobacteria in developed flat panel photobioreactor systems for the direct production of the solar fuel hydrogen. Further improvements in the strain used, environmental conditions employed, and growth, production and collection systems used, are needed before a sustainable and economical cyanobacterial based hydrogen production can be realized.


A framework for far-field infrared absorption microscopy beyond the diffraction limit.
A framework is proposed for infrared (IR) absorption microscopy in the far-field with a spatial resolution below the diffraction limit. The sub-diffraction resolution is achieved by pumping a transient contrast in the population of a selected vibrational mode with IR pulses that exhibit alternating central minima and maxima, and by probing the corresponding absorbance at the same wavelength with adequately delayed Gaussian pulses. Simulations have been carried out on the basis of empirical parameters emulating patterned thin films of octadecyltrichlorosilane and a resolution of 250 nm was found when probing the CH₂ stretches at 3.5 μm with pump energies less than ten times the vibrational saturation threshold.


A biophysical model for identifying splicing regulatory elements and their interactions.
Alternative splicing (AS) of precursor mRNA (pre-mRNA) is a crucial step in the expression of most eukaryotic genes. Splicing factors (SFs) play an important role in AS regulation by binding to the cis-regulatory elements on the pre-mRNA. Although many splicing factors (SFs) and their binding sites have been identified, their combinatorial regulatory effects remain to be elucidated. In this paper, we derive a biophysical model for AS regulation that integrates combinatorial signals of cis-acting splicing regulatory elements (SREs) and their interactions. We also develop a systematic framework for model inference. Applying the biophysical model to a human RNA-Seq data set, we demonstrate that our model can explain 49.1%-66.5% variance of the data, which is comparable to the best result achieved by biophysical models for transcription. In total, we identified 119 SRE pairs between different regions of cassette exons that may regulate exon or intron definition in splicing, and 77 SRE pairs from the same region that may arise from a long motif or two different SREs bound by different SFs. Particularly, putative binding sites of polypyrimidine tract-binding protein (PTB), heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and E/K are identified as interacting SRE pairs, and have been shown to be consistent with the interaction models proposed in previous experimental results. These results show that our biophysical model and inference method provide a means of quantitative modeling of splicing regulation and is a useful tool for identifying SREs and their interactions. The software package for model inference is available under an open source license.


Reliability and validity of the Thai Drug Hypersensitivity Quality of Life Questionnaire: a multi-center study.
To adapted the Drug Hypersensitivity Quality of Life (DrHy-Q) Questionnaire from Italian into Thai and assessed its validity and reliability. Prospectively recruited during January 2012-May 2017. Multicenter; six Thai tertiary university hospitals. Total of 306 patients with physician-diagnosed drug hypersensitivity. Internal consistency and test-retest reliability were evaluated among 68 participants using Cronbach's ɑ and intra-class correlation coefficient (ICC). The validity of Thai DrHy-Q was assessed among 306 participants who completed World Health Organization Quality of Life-BREF (WHOQOL-BREF-THAI). Construct and divergent validities were assessed for Thai DrHy-Q. Known-groups validity assessing discriminating ability was conducted in Thai DrHy-Q and WHOQOL-BREF-THAI. Validity; reliability; single vs. multiple drug allergy; non-severe cutaneous adverse reactions (SCAR) vs. SCAR. Thai DrHy-Q showed good reliability (Cronbach's ɑ = 0.94 and ICC = 0.8). Unidimensional factor structure was established by confirmatory factor analysis (CFI&TLI = 0.999, RMSEA = 0.02). Divergent validity was confirmed by weak correlation between Thai DrHy-Q and WHOQOL-BREF-THAI domains (Pearson's r = -0.41 to -0.19). Known-groups validity of Thai DrHy-Q was confirmed with significant difference between patients with and without life-threatening SCAR (P = 0.02) and patients with multiple implicated drug classes vs. those with one class (P < 0.01); while WHOQOL-BREF-THAI could differentiate presence of life-threatening SCAR (P < 0.01) but not multiple-drug allergy. Thai DrHy-Q was reliable and valid in evaluating quality of life among patients with drug hypersensitivity. Thai DrHy-Q was able to discriminate serious drug allergy phenotypes from non-serious manifestations in clinical practice and capture more specific drug-hypersensitivity aspects than WHOQOL-BREF-THAI.


Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.
Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.


The suicidal process and self-esteem.
It has not been made clear whether self-esteem is associated with the severity of suicidal behavior. To test the association between responses to a self-esteem inventory and levels of suicidal behavior as conceptualized in the notion of the suicide process. Questions on the severity of suicidal behavior over the lifespan (death wishes, ideation, plans, and attempts), as well as a self-esteem inventory, were administered to 227 university undergraduates. A negative relationship was found between the level of suicidality and self-esteem. As hypothesized, there were fewer cases in each succeeding level of seriousness of suicidal behavior. However, nearly all cases from any particular level were contained in the cohort of individuals who had displayed suicidal behavior at a less serious level. This suggests a possible progression through each of the stages of suicidal behavior, with very few cases showing a level of suicidal behavior that was not associated with a previous, less serious, form. It was hypothesized that early entry into the suicidal process may be indicated by low self-esteem, thus, allowing for a more timely preventive intervention.


Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma.
A valuable diagnostic adjunct and important prognostic parameter in alveolar rhabdomyosarcoma (ARMS) is the identification of translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), and the associated PAX3-FKHR and PAX7-FKHR fusion transcripts, respectively. Most RMS fusion gene type studies have been based on reverse transcriptase-polymerase chain reaction (RT-PCR) detection of the fusion transcript, a technique limited by RNA quality and failure of devised primer sets to detect unusual variants. As an alternative approach, we developed a fluorescence in situ hybridization (FISH) assay that can: (1) distinguish between the two most common ARMS-associated fusion genes; (2) identify potential unusual variant translocations; (3) assess histologic components in mixed alveolar/embryonal RMS; and (4) be performed on paraffinized tissue. FISH analyses of 75 specimens (40 ARMS, 16 ERMS, 8 mixed ARMS/ERMS, and 11 non-RMS tumors) using selected cosmid clone, bacterial, P1-derived, and yeast artificial chromosome probe sets were successful in all but two cases. Among specimens with informative results for both FISH and RT-PCR or standard karyotyping, PAX/FKHR classification results were concordant in 94.6% (53/56). The three discordant cases included one exhibiting a t(2;13) by FISH that was subsequently confirmed by repeat RT-PCR, a second showing a rearrangement of the PAX3 locus only (consistent with the presence of a PAX3 variant translocation), and a third revealing a t(2;13) by FISH that lacked this translocation cytogenetically. Both alveolar and embryonal components of the mixed ARMS/ERMS subtype were negative for PAX3, PAX7, and FKHR rearrangements, a surprising finding confirmed by RT-PCR and/or conventional karyotyping. These data demonstrate that FISH with newly designed probe sets is a reliable and highly specific method of detecting t(1;13) and t(2;13) in routinely processed tissue and may be useful in differentiating ARMS from other small round cell tumors. The findings also suggest that FISH may be a more sensitive assay than RT-PCR in some settings, capable of revealing variant translocations.


Potential Epigenetic Targets for Combating Alzheimer's Disease.
Memory remains an obligatory regime of the human brain, and impaired memory causes serious obstacles in our everyday life. Alzheimer's disease (AD) is one such neurodegenerative disease which mostly affects the elderly population, above the age of 60; marked by cognitive impairment of memory. Besides the known targets of AD against the several etiologies known to date, the zone of epigenetics has recently evolved as an ingenious field in AD. Epigenetic modifications do not affect DNA sequence but only long-term gene expression. Considering the complex multifactorial nature of AD, we herein discuss the various epigenetic targets which might give rise to potential therapeutic approaches. We reviewed the possible epigenetic targets for AD-like HDAC, Sirtuins, glial cells, miRNA and epigenetic modifications like DNA methylation. A deeper insight into these target areas can surely evolve AD diagnosis and therapeutics.


[Central, pulmonary and hepatic hemodynamics at the developmental stages of cardiopulmonary insufficiency].
The analysis of correlations between the time and speed parameters found out that in healthy subjects and patients with chronic nonspecific bronchitis (CNB) the blood flow in great hepatic vessels is provided by the amount of blood entering the aorta in the systole. When central hemodynamics is affected in the CNB exacerbation, this factor becomes essential also for the arterial inflow into middle-size and small branches of the hepatic artery. Persistent bronchial obstruction and labile pulmonary hypertension rise as a result of failure of adequate relations between systemic, pulmonary and hepatic hemodynamics. The condition of great arterial vessels of the liver gets dependent on lesser and greater circulation. The response of the middle-size and small branches of the hepatic artery in chronic obstructive bronchitis (functional class II) is independent of the vascular tone of the lesser and greater circulation. The conclusion is made that intrahepatic blood flow in patients with secondary pulmonary hypertension is regulated by vasoactive factors acting at the level of the organ (mainly kallikrein-kinin system and prostaglandins).


Serum levels of interleukin 1beta, interleukin 8 and tumour necrosis factor alpha as markers of gastric cancer.
Despite the efforts made, a serum marker reliable for the screening and follow-up of patients with gastric cancer has not yet been identified. The aim of this preliminary study was to test the role of pro-inflammatory cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha in patients with gastric cancer and in control groups. The statistical analysis of cytokines serum levels in the group with gastric cancer versus control groups has shown considerable differences (p < 0.001) in their mean rates. The results indicate that the cytokines interleukin 1beta, interleukin 8 and tumour necrosis factor alpha might perhaps act as diagnostic markers in patients with gastric cancer. Therefore, it is hypothesized that after more extended trials, their use in the screening and prognostic assessment of these patients could be a possibility.


Effects of acoustic nonlinearity on pulse-echo attenuation coefficient estimation from tissue-mimicking phantoms.
The ultrasonic attenuation coefficient (ACE) can be used to classify tissue state. Pulse-echo spectral-based attenuation estimation techniques, such as the spectral-log-difference method (SLD), account for beam diffraction effects using a reference phantom having a sound speed close to the sound speed of the sample. Methods like SLD assume linear propagation of ultrasound and do not account for potential acoustic nonlinear distortion of the backscattered power spectra in both sample and reference. In this study, the ACE of a sample was computed and compared using the SLD with two independent references (high attenuating and low attenuating phantoms but with similar B/A values) and over several pressure levels. Both numerical and physical tissue-mimicking phantoms were used in the study. The results indicated that the biases in ACE increased when using a reference having low attenuation, whereas the high attenuating reference produced more consistent ACE. Furthermore, increments in ACE vs input pressure were correlated to the log-ratio of Gol'dberg numbers between the sample and reference (R2=0.979 in simulations and R2=0.734 in experiments). Therefore, the results suggest that to reduce bias in ACE using spectral-based methods, both the sound speed and the Gol'dberg number of the reference phantom should be matched to the sample.


Identification of Avian and Hemoparasite DNA in Blood-Engorged Abdomens of Culex pipiens (Diptera; Culicidae) from a West Nile Virus Epidemic region in Suburban Chicago, Illinois.
Multiple mosquito-borne parasites cocirculate in nature and potentially interact. To understand the community of parasites cocirculating with West Nile virus (WNV), we screened the bloodmeal content of Culex pipiens L. mosquitoes for three common types of hemoparasites. Blood-fed Cx. pipiens were collected from a WNV-epidemic area in suburban Chicago, IL, from May to September 2005 through 2010. DNA was extracted from dissected abdomens and subject to PCR and direct sequencing to identify the vertebrate host. RNA was extracted from the head or thorax and screened for WNV using quantitative reverse transcriptase PCR. Seventy-nine engorged females with avian host origin were screened using PCR and amplicon sequencing for filarioid nematodes, Haemosporida, and trypanosomatids. Filarioid nematodes were identified in 3.8% of the blooded abdomens, Plasmodium sp. in 8.9%, Haemoproteus in 31.6%, and Trypanosoma sp. in 6.3%. The sequences from these hemoparasite lineages were highly similar to sequences from birds in prior studies in suburban Chicago. Overall, 50.6% of blood-fed Culex pipiens contained hemoparasite DNA in their abdomen, presumably from current or prior bloodmeals. Additionally, we detected hemoparasite DNA in the blooded abdomen of three of 10 Cx. pipiens infected with WNV.


Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications.
Myocarditis is the most common cause of heart failure in children. We investigated viral etiology of myocarditis/dilated cardiomyopathy (DCM) in children and correlated molecular findings with pathologic and clinical data. Polymerase chain reaction (PCR) or reverse transcription (RT)-PCR were used to analyze 59 endomyocardial biopsies from 48 consecutive young (<18 yrs) patients (pts) with clinical and histologic diagnosis of myocarditis and DCM, employing primers designed to amplify specific sequences of various DNA and RNA viruses. Nucleic acids were successfully extracted in 41 pts and viral genomes were found in 20 (49%): 12 out of 26 pts (46%) with myocarditis, 6 out of 13 (46%) pts with DCM, and both patients with endocardial fibroelastosis. Enteroviruses were more common in DCM (72%), whereas adenoviruses and enteroviruses shared the same rate (36%) in myocarditis. The mumps virus genome was detected in the two pts with endocardial fibroelastosis. More diffuse inflammatory infiltrates and myocyte damage as well as more impaired left ventricular end diastolic volume and shortening fraction were noted in viral positive cases. PCR positive pts had a worse outcome, resulting in transplantation or death. Three out of 8 pts with viral myocarditis who underwent cardiac transplantation had recurrent PCR-proven graft viral infection. Viral myocarditis/DCM appeared to be a more severe disease than nonviral forms. Enteroviruses were more common in DCM, whereas adenoviruses were as frequent as enteroviruses in myocarditis. Persistence of viral infection was associated with disease deterioration. Viral myocarditis relapsed after transplantation.


Effects of guanidinoacetic acid on growth performance, creatine metabolism and plasma amino acid profile in broilers.
The objective of this study was to assess the effects of guanidinoacetic acid (GAA) on growth performance, creatine deposition and blood amino acid (AA) profile on broiler chickens. In Exp. 1, a total of 540 one-day-old Arbor Acres male broilers (average initial body weight, 45.23 ± 0.35 g) were divided randomly into five treatments with six replicates of 18 chicks each. Broilers were fed corn-soybean meal-basal diets supplemented with 0, 600, 800, 1,000 or 1,200 mg/kg GAA for 42 days respectively. Results showed that dietary GAA inclusion increased average daily gain (ADG) and improved gain-to-feed ratio (G:F) from 1 to 42 days (p < 0.01). However, average daily feed intake was unaffected by dietary supplementation of GAA. As GAA inclusion increased, the contents of creatine in plasma and kidney were increased (linear, p < 0.01), while the contents of GAA and creatine in liver were decreased (linear, p < 0.01). Similarly, GAA supplementation was inversely related to concentrations of most essential AA in plasma. In Exp. 2, a total of 432 one-day-old Arbor Acres male broilers (average initial body weight, 39.78 ± 0.58 g) were divided randomly into four treatments with six replicates of 18 chicks each. Birds were fed a corn-soybean meal-basal diet supplemented with 0, 200, 400 or 600 mg/kg GAA for 42 days respectively. Dietary inclusion of 600 mg/kg GAA significantly increased ADG and G:F of broilers (p < 0.05). In conclusion, dietary supplementation of 600-1,200 mg/kg GAA can effectively improve the growth performance in broiler chickens by affecting creatine metabolism and utilization efficiency of essential AA, and 600 mg/kg GAA is the minimum dose for improving performance.


Platycodi radix beverage ameliorates postprandial lipemia response through lipid clearance of triglyceride-rich lipoprotein: A randomized controlled study in healthy subjects with a high-fat load.
Elevation of postprandial lipemia characterized by a rise in triglyceride (TG)-rich lipoproteins can increase the risk of atherogenesis. The objective of this study was to investigate postprandial lipemia response to a single dietary fat/sugar load test and monitor beneficial changes induced by the consumption of Platycodi radix (AP) beverage in healthy subjects. A total of 52 subjects were randomly assigned to either placebo or AP beverage group with a high-fat shake in a randomized controlled crossover trial. Postprandial blood was collected at 0, 1, 2, 4, and 6 h and analyzed for TG and lipoprotein lipase mass. Inhibition of pancreatic lipase was determined in vitro. AP inhibited pancreatic lipase activity in vitro (IC50 = 5 mg/mL). Compared to placebo beverage, AP beverage consumption with a high-fat shake induced significant increase of plasma lipoprotein lipase mass (P = 0.0111, β estimate = 4.2948) with significant reduction in very low-density lipoprotein (VLDL) TG concentration (P = 0.038, β estimate = -52.69) at 6 h. Based on significant correlation between high-fat dietary scores MEDFICTS and postprandial TG responses in VLDL (P = 0.0395, r = 0.2127), subgroup analysis revealed that 6 h-postprandial VLDL TG response was significantly decreased by AP consumption in subjects with MEDFICTS ≥ 40 (P = 0.0291, β estimate = -7214). AP beverage might have potential to alleviate postprandial lipemia through inhibiting pancreatic lipase activity and elevating lipoprotein lipase mass. Subgroup analysis revealed that subjects with high-fat dietary pattern could be classified as responders to AP beverage among all subjects.


Tumor necrosis factor-alpha eliminates binding of NF-Y and an octamer-binding protein to the lipoprotein lipase promoter in 3T3-L1 adipocytes.
TNF alpha has been shown to reduce lipoprotein lipase (LPL) activity in adipose tissue. Regulation of LPL by TNF alpha occurs at the level of LPL gene transcription and posttranscriptionally. To elucidate further the transcriptional mechanism of TNF alpha inhibition of LPL gene transcription, transfection analysis was used to locate the site(s) of the LPL promoter that imparts the TNF alpha response. Transient transfections using LPL promoter deletions fused to luciferase in differentiated 3T3-L1 cells with and without TNF alpha treatment indicated that a DNA region downstream of -180 bp confers the TNF alpha effect. Electrophoretic mobility shift assays using two 32P-labeled LPL probes spanning the region between -180 and +44 bp revealed the loss of several LPL DNA-protein interactions after TNF alpha treatment, including the binding of NF-Y to the CCAAT box and a protein to the octamer consensus sequence. Protein binding to the OCT-1 consensus sequence is unaffected until after 4 h of TNF alpha treatment. In addition, the amount of mRNA for OCT-1 is not altered with TNF alpha treatment. These results indicate that TNF alpha regulates at least two DNA-binding proteins on the proximal promoter, thereby inhibiting LPL gene transcription.


Existence of a powerful inhibitory mechanism in the medial region of caudal medulla--with special reference to the paramedian reticular nucleus.
Inhibitory actions of the medial trigon of the caudal medulla (ITM) with special reference to the paramedian reticular nucleus (PRN) were explored in cats under chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia. Stimulation with square wave pulses (80 Hz, 1 msec, 100-200 microA) produced a reduction of mean systemic arterial blood pressure (MSAP) of 15-90 mmHg, and change in heart rate (HR) that varied from mild increase of 15 to reduction of 85 beats/min. These responses were not affected by mid-collicular decerebration nor by bilateral vagotomy. Destruction of PRN did not change the resting MSAP, HR or baroreceptor reflex responses. Stimulation of PRN suppressed the sympathetic pressor and cardioacceleratory and the vagal bradycardia responses resulting from activating cardiovascular (CV) regulatory mechanisms in the hypothalamus, midbrain and medulla, or from activating the somatic or the baroreceptive afferents. Activation of the PRN suppressed the MSAP-increase produced by direct stimulation of the stellate or celiac ganglion. PRN stimulation could eliminate the pronounced CV reactions consequent either to asphyxial anoxia during occlusion of the trachea or to cerebral ischemia following occlusion of vertebral and carotid arteries. Furthermore, PRN activation could stop the general convulsion of the animal induced by picrotoxin, 4 mg/kg, IV. Our findings suggest that in the trigon area especially in the PRN, there resides an independent mechanism which exerts very powerful and broad inhibitory actions on the autonomic as well as somatic nervous system.


Hemorrhage from a right hepatic artery pseudoaneurysm: endovascular treatment with a coronary stent-graft.
To report a novel case demonstrating the successful endovascular treatment of a right hepatic artery pseudoaneurysm using a balloon-expandable coronary stent-graft. A 60-year-old woman underwent surgical treatment for a Klatskin tumor, but her postoperative course was complicated by serious blood loss. An emergent celiac angiogram through a right transfemoral approach demonstrated a small iatrogenic pseudoaneurysm in the proximal right hepatic artery. A 7-F guiding catheter was positioned at the origin of the celiac trunk, and a Jostent coronary stent-graft mounted on a 2.7-F, 4-mm x 30-mm balloon catheter was successfully placed across the aneurysm neck. The final angiogram demonstrated total exclusion of the pseudoaneurysm with preservation of the arterial lumen. The hemodynamic condition of the patient became stable. At 12-month follow-up, duplex scanning confirmed regular right hepatic artery patency and absence of thrombotic tissue or signs of infection around the stent-graft. For hepatic artery pseudoaneurysms, endovascular repair using small covered stents may be a viable alternative to transcatheter embolization. The use of coronary instruments facilitates treatment of vascular lesions in small caliber visceral vessels.


Diversity and distribution of fishes in tropical estuary Kuantan, Pahang, Malaysia.
A study on diversity and distribution of fish communities and water qualities were carried out from January 2009 to December 2010 to cover monsoon and non-monsoon at Kuantan estuary, Pahang, Malaysia. A total of 19 species of primary marine fish belong to 12 families were recorded. Out of 311 individuals the fish fauna was dominated by Ariidae followed by Lutjanidae and Lactaridae. As such Ariidae contributes 50% of the fish caught in the study area and its diversity index (H') was 0.97. A The Ariidae family consist of four (4) species; Arius maculatus, Arius sumatranus, Arius tenuispinis and Arius thalassinus. The Ariidae family can be found in all stations as they are euryhaline (highly tolerant to salinity) and this fish family are known to be a hardy estuarine catfish. Among all species in family Ariidae, Arius thalassinus was the most dominant (23%) among all species. As such collected species showed highest species diversity (0.34) followed by Arius tenuispinis (0.25) compared to other species. Arius tenuispinis alone contributed 11.90% among the samples caught from all stations. The fishes were caught and recorded highest in September-December. Pseudorhombus quinque ocellatus, Nibea soldado, Sardinella fimbriata, Toxotes jaculatrix, Dasyatis ushiei, Setipinna taty were the least dominant in the Kuantan estuary with 9.33% of total abundance. Physico-temperatures, such as temperature (22.03-30 degrees C), Conductivity (10.342.43 mS cm(-1)), TDS (0.06-26.34 mg L(-1)), salinity (0.05-29.09 ppt), DO (6.37-8.38 mg L(-1)), pH (4.97-8.03), Chl a (0.01-1.33 microg L(-1)), nitrite (0.01-0.08 mg L(-1)), nitrate (0.60-0.88 mg L(-1)), phosphate (0.24-0.40 mg L(-1)). Nevertheless, the study envisages that the water quality and fish diversity are still conducive in the Kuantan estuary. The fish diversity of Pahang estuary was high monsoon compared to non-monsoons. The station 4 (LKIM fishing boat jetty and adjacent Hospital Kuantan) is the most polluted area due to the presence of several outskirts could be alarming for the sustainable development of fish and other aquatic organisms in Kuantan estuary in the long run.


Psychometric Validation of the Portuguese Version of the Sexual Self-Consciousness Scale (SSCS).
The Sexual Self-Consciousness Scale (SSCS) is an instrument for assessing dispositional propensities for self-consciousness experienced in a sexual context, with wide application in both clinical and research settings. The objective of the current study was to test some psychometric characteristics of the Portuguese version of the SSCS using a convenience sample of 210 men and 210 women. Participants completed a sociodemographic questionnaire and the Portuguese version of the SSCS. A subsample of 87 participants was assessed at a second time point after a 2-week period for measuring test-retest reliability of the instrument. Confirmatory factor analysis identified two factors and replicated the structure of the original instrument. Measurement invariance was confirmed for men and women with overall index scores indicating a good fit in all models. Reliability analyses indicated that the factors possessed both satisfactory internal consistency and stability over time. The Portuguese version of the SSCS was shown to be a useful and adequate instrument to assess dispositional propensities for self-consciousness in sexual situations within the Portuguese-speaking population.


Transient overexpression of alpha-Ca2+/calmodulin-dependent protein kinase II in the nucleus accumbens shell enhances behavioral responding to amphetamine.
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is known to contribute to the expression of psychostimulant sensitization by regulating dopamine (DA) overflow from DA neuron terminals in the nucleus accumbens (NAcc). The present experiments explored the contribution of CaMKII in NAcc neurons postsynaptic to these terminals where it is known to participate in a number of signaling pathways that regulate responding to psychostimulant drugs. Exposure to amphetamine transiently increased alphaCaMKII levels in the shell but not the core of the NAcc. Thus, HSV (herpes simplex viral) vectors were used to transiently overexpress alphaCaMKII in NAcc neurons in drug-naive rats, and behavioral responding to amphetamine was assessed. Transiently overexpressing alphaCaMKII in the NAcc shell led to long-lasting enhancement of amphetamine-induced locomotion and self-administration manifested when alphaCaMKII levels were elevated and persisting long after they had returned to baseline. Enhanced locomotion was not observed after infection in the NAcc core or sites adjacent to the NAcc. Transient elevation of NAcc shell alphaCaMKII levels also enhanced locomotor responding to NAcc AMPA and increased phosphorylation levels of GluR1 (Ser831), a CaMKII site, both soon and long after infection. Similar increases in pGluR1 (Ser831) were observed both soon and long after exposure to amphetamine. These results indicate that the transient increase in alphaCaMKII observed in neurons of the NAcc shell after viral-mediated gene transfer and likely exposure to amphetamine leads to neuroadaptations in AMPA receptor signaling in this site that may contribute to the long-lasting maintenance of behavioral and incentive sensitization by psychostimulant drugs like amphetamine.


Transcription factor Sp1 recognizes promoter sequences from the monkey genome that are simian virus 40 promoter.
A 440-base-pair fragment of African green monkey genomic DNA shares homology with the transcriptional regulatory region of simian virus 40 (SV40) and has been reported to direct transcription in vivo. We find that two regions within this fragment bind the promoter-specific cellular transcription factor Sp1 and are protected in DNase protection ("footprinting") experiments. As in SV40, binding occurs in regions containing multiple copies of the sequence GGGCGG. These regions, when fused to the proximal, or "TATA box," element of the herpes simplex virus thymidine kinase promoter, are able to direct Sp1-dependent transcription in vitro. The finding that Sp1 is capable of productive interaction with sequences taken from a cellular promoter supports the idea that Sp1 may play a role in modulating transcription of cellular genes.


Aqueous two-phase flotation for primary recovery of bacteriocin-like inhibitory substance (BLIS) from Pediococcus acidilactici Kp10.
An aqueous two-phase flotation (ATPF) system based on polyethylene glycol (PEG) and sodium citrate (NaNO3C6H5O7·2H2O) was considered for primary recovery of bacteriocin-like inhibitory substance (BLIS) from Pediococcus acidilactici Kp10. The effects of ATPF parameters namely phase composition, tie-line length (TLL), volume ratio between the two phases (VR), amount of crude load (CL), pH, nitrogen gas flow rate (FR) and flotation time (FT) on the performance of recovery were evaluated. BLIS was mainly concentrated into the upper PEG-rich phase in all systems tested so far. The optimum conditions for BLIS purification, which composed of PEG 8000/sodium citrate, were: TLL of 42.6, VR of 0.4, CL of 22% (w/w), pH 7, average FT of 30min and FR of 20mL/min. BLIS was partially purified up to 5.9-fold with a separation efficiency of 99% under this optimal conditions. A maximum yield of BLIS activity of about 70.3% was recovered in the PEG phase. The BLIS from the top phase was successfully recovered with a single band in SDS-gel with molecular weight of about 10-15kDa. ATPF was found to be an effective technique for the recovery of BLIS from the fermentation broth of P. acidilactici Kp10.


Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia: a meta-analysis.
Aerosolized antibiotics are a widely recognized treatment for patients with cystic fibrosis (CF). We sought to clarify their role in the treatment of non-CF patients with nosocomial pneumonia by performing a meta-analysis of randomized controlled trials (RCTs) that compared administration of antimicrobials via the respiratory tract (with or without concurrent usage of systemic antibiotics) with control treatment. An extensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, Current Contents and bibliographies from retrieved publications was made. Five RCTs were included in the meta-analysis. Administration of antimicrobials via respiratory tract (either inhaled or endotracheally instilled) as opposed to control was associated with better treatment success in intention-to-treat [fixed effect model: odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.29-4.44; random effects model: OR = 2.75, 95% CI 1.06-7.17] and in clinically evaluable patients (fixed effect model: OR = 3.14, 95% CI 1.48-6.70; random effects model: OR = 3.07, 95% CI 1.15-8.19). There were no statistically significant differences between therapeutic regimens regarding all-cause mortality (fixed effect model: OR = 0.84, 95% CI 0.43-1.64; random effects model: OR = 0.71, 95% CI 0.27-1.88), microbiological success (fixed effect model: OR = 2.06, 95% CI 0.91-4.68; random effects model: OR = 2.23, 95% CI 0.64-7.71) and toxicity (fixed effect model: OR = 0.34, 95% CI 0.04-2.53; random effects model: OR = 0.36, 95% CI 0.04-3.16). The limited available evidence seems not to preclude a benefit from the administration of antimicrobial agents via the respiratory tract for treating nosocomial pneumonia.


Giant cell tumor of bone: oncological and functional results of long-term follow-up.
Giant cell tumor (GCT) of bone is a rare and unpredictable lesion. Its standard treatment has ranged from surgical curettage to wide resection and varying oncological and functional results have been reported. A retrospective review of 47 patients (17 males and 30 females) with GCT of bone was performed to evaluate the oncological and functional results. The patients were followed up for at least 5 years. The average age of the patients was 32 years (range 15-66 years). The tumor sites were distal femur in 15 cases, proximal tibia in 10, distal radius in five, spinal column in four, proximal femur in three, proximal humerus in three, proximal fibula in two, pelvis in two and others in three. Enneking's surgical stages were Stage 1 in three, Stage 2 in 34 and Stage 3 in 10 cases. In these 47 patients, 80 surgical procedures were performed. The rate of local recurrence was 75% in the 28 patients undergoing intralesional excision, 50% in those receiving excision and curettage and 0% in those receiving wide resection. Although there was no statistical significance, surgical stages tended to be correlated with the local recurrence rate (Stage 1, 0%; Stage 2, 53%; Stage 3, 70%). Functional evaluation was performed according to the most recent system of the Musculoskeletal Tumor Society. Functional results of the patients with extremity tumors were 28.2 (average) in those undergoing intralesional excision, 30 (average) in those receiving excision and curettage and 27.1 (average) in those receiving wide resection. Functional results were significantly correlated with the initial surgical stages (Stage 1, 30; Stage 2, 27.5; Stage 3, 24.4; Kruskal-Wallis test, P = 0.016). To preserve good function of the extremities and avoid local recurrence, we consider that intralesional excision with adjunctive therapy such as phenol cauterization should be employed for the treatment of benign GCT of bone.


Modeling transient particle transport in transient indoor airflow by fast fluid dynamics with the Markov chain method.
It is crucial to accurately and efficiently predict transient particle transport in indoor environments to improve air distribution design and reduce health risks. For steady-state indoor airflow, fast fluid dynamics (FFD) + Markov chain model increased the calculation speed by around seven times compared to computational fluid dynamics (CFD) + Eulerian model and CFD + Lagrangian model, while achieving the same level of accuracy. However, the indoor airflow could be transient, if there were human behaviors involved like coughing or sneezing and air was supplied periodically. Therefore, this study developed an FFD + Markov chain model solver for predicting transient particle transport in transient indoor airflow. This investigation used two cases, transient particle transport in a ventilated two-zone chamber and a chamber with periodic air supplies, for validation. Case 1 had experimental data for validation and the results showed that the predicted particle concentration by FFD + Markov chain model matched well with the experimental data. Besides, it had similar accuracy as the CFD + Eulerian model. In the second case, the prediction by large eddy simulation (LES) was used for validating the FFD. The simulated particle concentrations by the Markov chain model and the Eulerian model were similar. The simulated particle concentrations by the Markov chain model and the Eulerian model were similar. The computational time of the FFD + Markov chain model was 7.8 times less than that of the CFD + Eulerian model.


Alignment parameters of foveal cones.
In the fovea we measured the orientation and directional characteristics of photoreceptors with an optical technique in a group of 29 subjects. At 6 deg eccentricity, we determined the direction of the normal to the inner limiting membrane (ILM) by analyzing light reflected specularly by the ILM. We found a strong correlation between the orientation of photoreceptor axes and the direction of the normal to the ILM. Therefore, we cannot answer the question of the mechanism of photoreceptor alignment without taking into account the direction of the normal to the underlying retinal pigment epithelium, in addition to phototropic and apodization processes. For a wavelength of 532 nm, the mean value of the directionality factor rho was 0.212 mm(-2) (SD: 0.026 mm(-2)) when measured at the fovea (2 deg sample field). We look for reasons likely to explain the discrepancy between rho values given by different optical methods.


Heat tolerance may determine activity time in coprophagic beetle species (Coleoptera: Scarabaeidae).
Although reports have documented loss of species diversity and ecological services caused by stressful temperature changes that result from climate change, some species cope through behavioral compensation. As temperatures and magnitudes of temperature extremes increase, animals should compensate to maintain fitness (such as through temporary behavioral shifts in activity times). Appropriate timing of activity helps avoid competition across species. Although coprophagic dung beetles exhibit species-specific temporal activity times, it is unknown whether temperature drives evolution of these species-specific temporal activity times. Using nine dung beetle species (three each of diurnal, crepuscular, and nocturnal species), we explored differences in heat stress tolerance measured as critical thermal maxima (CTmax ; the highest temperature allowing activity) and heat knockdown time (HKDT; survival time under acute heat stress) across these species, and examined the results using a phylogenetically informed approach. Our results showed that day-active species had significantly higher CTmax (diurnal > crepuscular = nocturnal species), whereas crepuscular species had higher HKDT (crepuscular > nocturnal > diurnal species). There was no correlation between heat tolerance and body size across species with distinct temporal activity, and no significant phylogenetic constraint for activity. Species with higher CTmax did not necessarily have higher HKDT, which indicates that species may respond differently to diverse heat tolerance metrics. Acute heat tolerance for diurnal beetles indicates that this trait may constrain activity time and, under high acute temperatures with climate change, species may shift activity times in more benign environments. These results contribute to elucidate the evolution of foraging behavior and management of coprophagic beetle ecosystem services under changing environments.


Corticosteroids for Preventing Caustic Esophageal Strictures: Systematic Review and Meta-analysis.
Caustic ingestion can have a complicated clinical course. Corticosteroids are widely used but there is uncertainty about its role in preventing esophageal stricture formation following caustic ingestion. This systematic review and meta-analysis assessed the available clinical evidence regarding the efficacy and safety of corticosteroids for preventing esophageal strictures following caustic injury. We assessed randomized controlled trials (RCTs) that compared corticosteroids versus no corticosteroids in the prevention of esophageal stricture formation following caustic ingestion. We searched the following databases from inception to March 2017: PubMed, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers retrieved eligible articles, assessed risk of bias, and performed data extraction. The main outcome measure was the prevention of esophageal stricture formation. The search identified 763 citations. Three RCTs involving 244 participants met the inclusion criteria. There was no benefit of corticosteroids in the prevention of esophageal strictures following the ingestion of caustic materials (risk ratio [RR] = 0.63, 95% CI = 0.29-1.37). The available evidence does not support the use of corticosteroids for the prevention of esophageal strictures following caustic ingestion. The overall quality of the evidence is limited because of methodological weaknesses and small sample sizes in the primary studies.


Acupuncture for multiple sclerosis: A literature review.
Acupuncture as a complementary and alternative medicine (CAM) modality appears to be a helpful integrative therapy for multiple sclerosis (MS). Due to the chronicity of the disease and persistent symptoms, a large number of patients seek to use CAM for the MS treatment. Therefore, the present review aimed to determine the effectiveness of acupuncture in the treatment of multiple sclerosis. PUBMED database was searched for English articles (at least English abstracts) in September 2021, including all articles published since the earliest literature until September 2021. Review articles were searched for relevant data. The searched keywords in titles and abstracts included ((acupuncture) OR (electroacupuncture)) AND (multiple sclerosis). Totally, out of 75 studied articles, 31 were included in this research. The advantages of acupuncture are mainly reflected in regulating neuro-immune system, improving the quality of life, reducing fatigue, improving the bladder function, reducing the spasm and pain of the limbs, delaying the progression of the disease, and reducing relapses. According to the review of the recent articles, traditional Chinese acupuncture and scalp acupuncture appear to help improve the symptoms of multiple sclerosis (including fatigue, neural functional deficits, pain, gait impairments, and bladder dysfunction) and reduce relapses. Therefore, acupuncture could be used as an integrative therapy in patients with MS.


Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation.
PURPOSE Fibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to determine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation. METHODS An institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All catheters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagulation and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined. RESULTS Patients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median catheter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respectively. Time to fibrin sheath formation was not significantly associated with hematocrit (P =.16), platelet count (0.12), PT (P =.51), or INR (P =.74). CONCLUSION Anticoagulation has no significant benefit in delaying sheath formation in patients with tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter placement were also not associated with catheter dwell time.


Measuring progress to healing: A challenge and an opportunity.
Complete healing is problematic as an endpoint for evaluating interventions for wound healing. The great heterogeneity of wounds makes it difficult to match groups, and this is only possible with multivariate stratification and/or very large numbers of subjects. The substantial time taken for wounds to heal necessitates a very lengthy study. Consequently, high quality randomised controlled trials demonstrating an effect of an intervention to a satisfactory level of statistical significance and with a satisfactory level of generalisability are extremely rare. This study determines that the healing of venous leg ulcers receiving multi-component compression bandaging follows a linear trajectory over a 4-week period, as measured by gross area healed, percentage area healed, and advance of the wound margin. The linear trajectories of these surrogates make it possible to identify an acceleration in healing resulting from an intervention, and allows self-controlled or crossover designs with attendant advantages of statistical power and speed. Of the metrics investigated, wound margin advance was the most linear, and was also independent of initial ulcer size.


Efficacy of viscous budesonide slurry for prevention of esophageal stricture formation after complete endoscopic mucosal resection of short-segment Barrett's neoplasia.
Complete endoscopic resection (CER) of short-segment Barrett's esophagus with high grade dysplasia (HGD) and early esophageal adenocarcinoma (EEA) is a precise staging tool and achieves durable disease control. The major drawback is development of post-endoscopic resection esophageal stricture (PERES). No effective therapy to prevent PERES has been described. Viscous budesonide slurry (VBS) may have a role in the prevention of PERES by suppressing the post-CER inflammatory process. The study aim was to evaluate the efficacy of VBS for the prevention of PERES. Prospective data were collected on patients referred for CER of HGD or EEA. After January 2012, patients routinely received VBS (two 0.5-mg/2-mL budesonide respules mixed with sucralose) twice daily for 6 weeks following each stage of the CER schedule. All patients received high dose proton pump inhibitor therapy for the duration of CER and the following 3 months. Patients had no other intervention to prevent PERES. A validated dysphagia score was used (0 - 4, no dysphagia to aphagia). Endoscopic dilation was performed for dysphagia. Patients receiving VBS were compared with historical controls. The primary endpoint was the need for dilation. Between January 2008 and January 2015, 104 of 116 eligible patients completed CER. The VBS group (n = 29) and non-VBS group (n = 75) had similar patient, disease, and procedural characteristics. Dilations were needed in 13.8 % vs. 37.3 % (P = 0.03), with a median of one vs. two procedures (P = 0.01), and median dysphagia score during CER of 0 vs. 1 (P = 0.02) in the VBS and non-VBS groups, respectively. No VBS-related adverse events were noted. In this pilot study VBS significantly reduced PERES and shortened the dilation program after CER.


Study on mitigating membrane fouling based on precursor and flocculant Alb matching in EC/O-UF system.
One of the effective ways to remove halogenated disinfection by-products (DBPs) from drinking water is the application of ultrafiltration technology. However, membrane fouling is an important factor affecting the service life and treatment effect. In this study, the electrocoagulation/oxidation-ultrafiltration (EC/O-UF) process was used to remove the precursor substance that produced DBPs, i.e. dissolved organic matters (DOMs). Operating parameters were optimized from the matching of different flocculant morphology to low concentration DOM. The degree of membrane fouling was characterized by analyzing DOMs concentration and membrane flux. The results showed that the optimal conditions for the production of Alb were: current density 10 A/m2, hydraulic retention time 10 min, and initial pH 5.0-7.0. Under these conditions, the production of flocculant Alb could reach 58-61%, 94-97% DOMs were removed by EC/O-UF.


Social relations in a mixed group of mules, ponies and donkeys reflect differences in equid type.
Donkeys and mules are frequently kept as companion animals for horses and ponies, with these different equids often being considered a homogenous group. However, the extent to which domestic equids form inter-specific bonds and display similar social behaviour when living in a mixed herd has not previously been studied. Here we compare the social organization of these three (sub)species when housed together, providing the first systematic analysis of how genetic hybridization is expressed in the social behaviour of mules. A group of 16 mules, donkeys and ponies was observed for 70h and preferred associates, dominance rank and the linearity of the group's hierarchy was determined. The different equids formed distinct affiliative groups that were ordered in a linear hierarchy with ponies as the most dominant, mules in the middle ranks and donkeys in the lowest ranks. Within each equid subgroup, the strength of the hierarchy also varied. Thus in the present study, the three (sub)species displayed different social organization and levels of dominance and preferred to associate with animals of the same equid type, given the opportunity. These results suggest that different domestic equid (sub)species display variations in social behaviour that are likely to have a strong genetic basis.


Glucose and insulin metabolism in twins: influence of zygosity and birth weight.
Several epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.


Understanding excessive SNR loss in hearing-impaired listeners.
Traditional audiometric measures, such as pure-tone thresholds or unaided word-recognition in quiet, appear to be of marginal use in predicting speech understanding by hearing-impaired (HI) individuals in background noise with or without amplification. Suprathreshold measures of auditory function (tolerance of noise, temporal and frequency resolution) appear to contribute more to success with amplification and may describe more effectively the distortion component of hearing. However, these measures are not typically measured clinically. When combined with measures of audibility, suprathreshold measures of auditory distortion may provide a much more complete understanding of speech deficits in noise by HI individuals. The primary goal of this study was to investigate the relationship among measures of speech recognition in noise, frequency selectivity, temporal acuity, modulation masking release, and informational masking in adult and elderly patients with sensorineural hearing loss to determine whether peripheral distortion for suprathreshold sounds contributes to the varied outcomes experienced by patients with sensorineural hearing loss listening to speech in noise. A correlational study. Twenty-seven patients with sensorineural hearing loss and four adults with normal hearing were enrolled in the study. The data were collected in a sound attenuated test booth. For speech testing, subjects' verbal responses were scored by the experimenter and entered into a custom computer program. For frequency selectivity and temporal acuity measures, subject responses were recorded via a touch screen. Simple correlation, step-wise multiple linear regression analyses and a repeated analysis of variance were performed. Results showed that the signal-to-noise ratio (SNR) loss could only be partially predicted by a listener's thresholds or audibility measures such as the Speech Intelligibility Index (SII). Correlations between SII and SNR loss were higher using the Hearing-in-Noise Test (HINT) than the Quick Speech-in-Noise test (QSIN) with the SII accounting for 71% of the variance in SNR loss for the HINT but only 49% for the QSIN. However, listener age and the addition of suprathreshold measures improved the prediction of SNR loss using the QSIN, accounting for nearly 71% of the variance. Two standard clinical speech-in-noise tests, QSIN and HINT, were used in this study to obtain a measure of SNR loss. When administered clinically, the QSIN appears to be less redundant with hearing thresholds than the HINT and is a better indicator of a patient's suprathreshold deficit and its impact on understanding speech in noise. Additional factors related to aging, spectral resolution, and, to a lesser extent, temporal resolution improved the ability to predict SNR loss measured with the QSIN. For the HINT, a listener's audibility and age were the only two significant factors. For both QSIN and HINT, roughly 25-30% of the variance in individual differences in SNR loss (i.e., the dB difference in SNR between an individual HI listener and a control group of NH listeners at a specified performance level, usually 50% word or sentence recognition) remained unexplained, suggesting the need for additional measures of suprathreshold acuity (e.g., sensitivity to temporal fine structure) or cognitive function (e.g., memory and attention) to further improve the ability to understand individual variability in SNR loss.


Migration and relationship power among Mexican women.
Our study drew on original data collected in Durham, NC, and four sending communities in Mexico to examine differences in women's relationship power that are associated with migration and residence in the United States. We analyzed the personal, relationship, and social resources that condition the association between migration and women's power and the usefulness of the Relationship Control Scale (RCS) for capturing these effects. We found support for perspectives that emphasize that migration may simultaneously mitigate and reinforce gender inequities. Relative to their nonmigrant peers, Mexican women in the United States average higher emotional consonance with their partners, but lower relationship control and sexual negotiation power. Methodologically, we found that the RCS is internally valid and useful for measuring the impact of resources on women's power. However, the scale appears to combine diverse dimensions of relationship power that were differentially related to migration in our study.


Left branch of portal vein thrombosis in a liver transplant recipient with donation after cardiac death donor: A case report.
Portal vein thrombosis (PVT) is one of the most severe complications after liver transplantation, which usually causes graft loss and recipient mortality. The founding of the embolic branch of portal system and its result are not well described in the literature. We report here an unusual case of complete right branch thrombosis of portal vein after orthotopic liver transplantation from a donation after cardiac death donor, without obvious malaise. The branch thrombosis of portal vein was detected by Doppler ultrasound 11 days after transplantation, followed by angiography for further verification. After treatment with urgent indwelling catheter thrombolysis with urokinase, results improved and the patient showed stable liver function. The patient has been in remission for 22 months with normal graft function. In this case report, we show that frequent ultrasound inspection should be adopted to detect the unobstructed vessel in the early stage of liver transplantation, and local thrombolytic therapy can be used to prevent liver injury and keep the vessel open.


APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast.
Human cells harbor a variety of factors that function to block the proliferation of foreign nucleic acid. The APOBEC3G enzyme inhibits the replication of retroviruses by deaminating nascent retroviral cDNA cytosines to uracils, lesions that can result in lethal levels of hypermutation. Here, we demonstrate that APOBEC3G is capable of deaminating genomic cytosines in Saccharomyces cerevisiae. APOBEC3G expression caused a 20-fold increase in frequency of mutation to canavanine-resistance, which was further elevated in a uracil DNA glycosylase-deficient background. All APOBEC3G-induced base substitution mutations mapped to the nuclear CAN1 gene and were exclusively C/G --> T/A transition mutations within a 5'-CC consensus. The APOBEC3G preferred sites were found on both strands of the DNA duplex, but were otherwise located in hotspots nearly identical to those found previously in retroviral cDNA. This unique genetic system further enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves the deamination of cDNA cytosines. Thus, these data expand the range of likely APOBEC3 targets to include nuclear DNA and endogenous retroelements, which have pathological and physiological implications, respectively. We postulate that the APOBEC3-dependent innate cellular defense constitutes a tightly regulated arm of a conserved mobile nucleic acid restriction mechanism that is poised to limit internal as well as external assaults.


Pain in irritable bowel syndrome: Does anything really help?
Pain relief remains a significant challenge in the management of irritable bowel syndrome (IBS): "Does anything really help relieve the pain in patients with IBS?". Interventions aimed at pain relief in patients with IBS include diet, probiotics or antibiotics, antidepressants, antispasmodics, and drugs targeting specific gastrointestinal receptors such as opioid or histamine receptors. In the systematic review and meta-analysis published in this journal, Lambarth et al. examined the literature on the role of oral and parenteral anti-neuropathic agents in the management of pain in patients with IBS. This review article appraises their assessment of the efficacy of the anti-neuropathic agents amitriptyline, pregabalin, gabapentin, and duloxetine in the relief of abdominal pain or discomfort, and impact on overall IBS severity and quality of life. This commentary provides an update of current evidence on the efficacy of the dietary and pharmacological treatments that are available or in development, as well psychological and cognitive behavioral therapy for pain in IBS. Advances in recent years augur well for efficacious treatments that may expand the therapeutic arsenal for pain in IBS.


Injury potential of thrown sharp kitchen and household utensils.
We examined the possibility of inflicting serious injuries with sharp objects in an experimental setting by throwing four sharp objects from different distances and with different throwing techniques. Using an overarm-handle (OA/H), overarm-blade (OA/B), underarm-handle (UA/H), underarm-blade (UA/B) and thrust (T/H) throwing technique, 10 adults (sex ratio 1:1) threw a chef's knife, a skinning knife, a paring knife and office scissors from 4 m and 2 m distance at synthetic abdomen models made of 10% gelatin covered with synthetic skin. The amount of hits and penetrations of the target and their penetration depth were noted, as was the rotation of the blade tip towards the target along its flight trajectory. The chef's knife injury/hit ratio was 0.167/4 m and 0.160/2 m; the skinning knife recorded an injury/hit ratio of 0.087/4 m and 0.153/2 m; the paring knife of 0.087/4 m and 0.113/2 m; and the scissors 0.087/4 m and 0.067/2 m. Mean penetration depths were as follows: the chef's knife: 4 m, 4.42 cm, 2 m, 3.41 cm; the skinning knife: 4 m, 4.19 cm, 2 m, 4.11 cm; the paring knife: 4 m, 1.62 cm, 2 m, 1.55 cm; and the scissors: 4 m, 2.08 cm, 2 m, 0.95 cm. Handle-throw penetration-depths were: 4 m: 3.77 cm and 2 m: 2.86 cm; blade-throw depths were: 4 m: 3.14 cm and 2 m: 2.69 cm. Overarm-throw penetration-depths were: 4 m: 3.62 cm and 2 m: 3.25 cm; and underarm-throw penetration-depths were 4 m: 3.30 cm and 2 m: 2.30 cm. No thrust-throws with the paring knife and scissors could pierce the target. The tips pointed toward the target at angles of 60°-120°, earlier in handle-throws than blade-throws, especially with the paring knife and the scissors. When thrown, especially with a handle-held technique, heavier objects pierced more often and more deeply. Thrust-throws at short distances are unlikely to pierce a human.


Nicotiana glauca poisoning in ostriches (Struthio camelus).
Putative Nicotiana glauca (wild tobacco) poisoning was diagnosed in a flock of ostriches near Oudtshoorn, South Africa. Post mortem examinations (n = 7) were performed on ostriches (Struthio camelus) that had died. Suspicious leaf remnants (weighing 80-770 g), packed in a layer on top of other plant material, were carefully separated from the proventricular content and submitted for chemical determination of anabasine, the major toxic principle contained by this plant. A standard solid phase extraction method was used followed by an optimised liquid chromatography-mass spectrometry procedure. Anabasine was detected in the leaf remnants (114-177 microg/g dry weight) removed from the proventriculus of the ostriches that succumbed as well as in control N. glauca leaves (193 microg/g dry weight). The analytical methods used in this study revealed the presence of anabasine in the suspicious leaf remnants, indicating that the birds had been exposed to N. glauca and had died of this poisoning.


Obesity and prostate cancer: collateral damage in the battle of the bulge.
Prostate cancer is the most common non-cutaneous malignancy diagnosed in US men. With the increasing prevalence of obesity, it is of interest how this condition impacts prostate cancer. However, only recently has the relationship between obesity and prostate cancer been earnestly studied by investigators. Indeed, the relationship between obesity and prostate cancer appears to be complex one. Therefore, we sought to review the most recent and relevant epidemiological data discussing the link between prostate cancer and obesity. In this review, we will discuss both "biological" and "non-biological" means by which obesity may potentially impact prostate cancer.


Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro.
Cannabinoid (CB) ligands have demonstrated neuroprotective properties. In this study we compared the effects of a diverse set of CB ligands against β amyloid-mediated neuronal toxicity and activated microglial-conditioned media-based neurotoxicity in vitro, and compared this with a capacity to directly alter β amyloid (Aβ) fibril or aggregate formation. Neuroblastoma (SH-SY5Y) cells were exposed to Aβ1-42 directly or microglial (BV-2 cells) conditioned media activated with lipopolysaccharide (LPS) in the presence of the CB1 receptor-selective agonist ACEA, CB2 receptor-selective agonist JWH-015, phytocannabinoids Δ(9)-THC and cannabidiol (CBD), the endocannabinoids 2-arachidonoyl glycerol (2-AG) and anandamide or putative GPR18/GPR55 ligands O-1602 and abnormal-cannabidiol (Abn-CBD). TNF-α and nitrite production was measured in BV-2 cells to compare activation via LPS or albumin with Aβ1-42. Aβ1-42 evoked a concentration-dependent loss of cell viability in SH-SY5Y cells but negligible TNF-α and nitrite production in BV-2 cells compared to albumin or LPS. Both albumin and LPS-activated BV-2 conditioned media significantly reduced neuronal cell viability but were directly innocuous to SH-SY5Y cells. Of those CB ligands tested, only 2-AG and CBD were directly protective against Aβ-evoked SH-SY5Y cell viability, whereas JWH-015, THC, CBD, Abn-CBD and O-1602 all protected SH-SY5Y cells from BV-2 conditioned media activated via LPS. While CB ligands variably altered the morphology of Aβ fibrils and aggregates, there was no clear correlation between effects on Aβ morphology and neuroprotective actions. These findings indicate a neuroprotective action of CB ligands via actions at microglial and neuronal cells.


A localized coverage preserving protocol for wireless sensor networks.
In a randomly deployed and large scale wireless sensor network, coverage-redundant nodes consume much unnecessary energy. As a result, turning off these redundant nodes can prolong the network lifetime, while maintaining the degree of sensing coverage with a limited number of on-duty nodes. None of the off-duty eligibility rules in the literature, however, are sufficient and necessary conditions for eligible nodes. Hence redundancy or blind points might be incurred. In this paper we propose a complete Eligibility Rule based on Perimeter Coverage (ERPC) for a node to determine its eligibility for sleeping. ERPC has a computational complexity of O(N(2)log(N)), lower than the eligibility rule in the Coverage Control Protocol (CCP), O(N(3)), where N is the number of neighboring nodes. We then present a Coverage Preserving Protocol (CPP) to schedule the work state of eligible nodes. The main advantage of CPP over the Ottawa protocol lies in its ability to configure the network to any specific coverage degree, while the Ottawa protocol does not support different coverage configuration. Moreover, as a localized protocol, CPP has better adaptability to dynamic topologies than centralized protocols. Simulation results indicate that CPP can preserve network coverage with fewer active nodes than the Ottawa protocol. In addition, CPP is capable of identifying all the eligible nodes exactly while the CCP protocol might result in blind points due to error decisions. Quantitative analysis and experiments demonstrate that CPP can extend the network lifetime significantly while maintaining a given coverage degree.


Utilization and case-mix impacts of per case payment in Maryland.
Maryland has simultaneously operated per case and per service hospital payment systems since 1976 with varying levels of stringency in setting per case rates. Regression analyses of this experience are used to compare the impacts of these systems on admissions, length of stay, and case-mix costliness from July 1, 1976 to June 30, 1981. Our results indicate a positive effect on admissions and negative effects on case mix and length of stay for the per case payment approach relative to the per service approach. More stringent levels of per case payment are associated with stronger utilization responses.