Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury.
To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury. This matched cohort study included patients who were admitted with a traumatic injury between 1 March 2017 and 30 October 2017. The hospital pharmacy database was used to identify patients who received dronabinol (cases), and they were matched 1:1 to patients who did not receive dronabinol (controls) using age, cause of injury and hospital length of stay. The primary outcome, change in opioid consumption, was calculated using morphine milligram equivalents (MME). The change in MME was calculated for cases as total MME over 48 hours with adjunctive dronabinol minus 48 hours prior to dronabinol, and for controls as total MME 48-96 hours from admission minus 0-48 hours from admission. Data are presented as mean and SE or median and IQR. Statistical analysis was performed using paired t-tests and McNemar's tests. There were 66 patients included: 33 cases and 33 matched controls. Dronabinol was initiated 55 (28-107) hours from admission. Cases and controls were well matched. Cases had a significant reduction in opioid consumption with adjunctive dronabinol (-79 (20) MME, p<0.001), while opioid consumption was unchanged for controls (-9 (20) MME, p=0.63). This resulted in a ninefold greater reduction in opioid consumption for cases versus controls that was statistically different between pairs (p=0.02). Nineteen (58%) cases reported using marijuana; in this subset, opioid consumption was reduced with adjunctive dronabinol (-97 (24) MME, p<0.001) versus a non-significant increase in opioid consumption in matched controls (11 (29) MME, p=0.70); difference between groups, p=0.01. The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury. The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users. III.


Lung cancer: developmental networks gone awry?
High-throughput genomic data for both lung development and lung cancer continue to accumulate. Significant molecular intersection between these two processes has been hypothesized due to overlap in phenotypes and genomic variation. Examining the network biology of both cancer and development of the lung may shed functional light on the individual signaling modules involved. Stem cell biology may explain a portion of this network intersection and consequently studying lung organogenesis may have relevance for understanding lung cancer. This review summarizes our understanding of the potential overlapping mechanisms involved in lung development and lung tumorigenesis.


Fibromyalgia and chronic fatigue: the holistic perspective.
Fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) are not new conditions, but they are receiving more attention as more research is conducted. These two conditions are primarily women's health problems. In some instances, there may be a genetic predisposition for these conditions. The impact of FMS and CFS can be devastating both physically and emotionally. The treatment plan must be interdisciplinary and holistic and include alternative therapies if the client and family are to be truly supported and helped in coping with these chronic conditions.


The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus.
NIH-3T3 cells, which are resistant to reovirus infection, became susceptible when transformed with activated Sos or Ras. Restriction of reovirus proliferation in untransformed NIH-3T3 cells was not at the level of viral gene transcription, but rather at the level of viral protein synthesis. An analysis of cell lysates revealed that a 65 kDa protein was phosphorylated in untransformed NIH-3T3 cells, but only after infection with reovirus. This protein was not phosphorylated in infected or uninfected transformed cells. The 65 kDa protein was determined to be the double-stranded RNA-activated protein kinase (PKR), whose phosphorylation leads to translation inhibition. Inhibition of PKR phosphorylation by 2-aminopurine, or deletion of the Pkr gene, led to drastic enhancement of reovirus protein synthesis in untransformed cells. The emerging picture is one in which early viral transcripts trigger PKR phosphorylation in untransformed cells, which in turn leads to inhibition of translation of viral genes; this phosphorylation event is blocked by an element(s) in the Ras pathway in the transformed cells, allowing viral protein synthesis to ensue. The usurpation of the Ras signaling pathway therefore constitutes the basis of reovirus oncolysis.


Feeding strategies and competition between terrestrial Haemadipsa leeches (Euhirudinea: Arhynchobdellida) in Danum Valley rainforest (Borneo, Sabah).
Haemadipsid leeches are among the most successful terrestrial invertebrates in Bornean rainforests. They are very common ectoparasites of vertebrates, and their abundance has facilitated the conduction of numerous projects in the fields of ecology, zoogeography and taxonomy. We undertook research on two species inhabiting lowland dipterocarp forest, Haemadipsa picta Moore, 1929 and Haemadipsa subagilis (Moore, 1929), in order to address the following questions: (a) is there a difference in leech abundance between trails and off-trails?; (b) is ambush location dependent on specimen size or is species-specific?; (c) is intra- and interspecific competition limited by differences in foraging behaviours or vertical niche partitioning? Our results clearly show that H. picta is more abundant on trails than on off-trails and is vertically dispersed within the understory; the size of a specimen is strongly correlated with plant height. Haemadipsa subagilis was found not to exhibit such patterns. We suggest a possible lowering of interspecific competition between these species as a result of: (i) size-dependent dispersion of H. picta (together with reduction of intraspecific competition); and (ii) habitat specialisation of H. subagilis. Moreover, we provide new observations on their foraging behaviour.


Detectability comparison between a high energy x-ray phase sensitive and mammography systems in imaging phantoms with varying glandular-adipose ratios.
The objective of this study was to demonstrate the potential benefits of using high energy x-rays in comparison with the conventional mammography imaging systems for phase sensitive imaging of breast tissues with varying glandular-adipose ratios. This study employed two modular phantoms simulating the glandular (G) and adipose (A) breast tissue composition in 50 G-50 A and 70 G-30 A percentage densities. Each phantom had a thickness of 5 cm with a contrast detail test pattern embedded in the middle. For both phantoms, the phase contrast images were acquired using a micro-focus x-ray source operated at 120 kVp and 4.5 mAs, with a magnification factor (M) of 2.5 and a detector with a 50 µm pixel pitch. The mean glandular dose delivered to the 50 G-50 A and 70 G-30 A phantom sets were 1.33 and 1.3 mGy, respectively. A phase retrieval algorithm based on the phase attenuation duality that required only a single phase contrast image was applied. Conventional low energy mammography images were acquired using GE Senographe DS and Hologic Selenia systems utilizing their automatic exposure control (AEC) settings. In addition, the automatic contrast mode (CNT) was also used for the acquisition with the GE system. The AEC mode applied higher dose settings for the 70 G-30 A phantom set. As compared to the phase contrast images, the dose levels for the AEC mode acquired images were similar while the dose levels for the CNT mode were almost double. The observer study, contrast-to-noise ratio and figure of merit comparisons indicated a large improvement with the phase retrieved images in comparison to the AEC mode images acquired with the clinical systems for both density levels. As the glandular composition increased, the detectability of smaller discs decreased with the clinical systems, particularly with the GE system, even at higher dose settings. As compared to the CNT mode (double dose) images, the observer study also indicated that the phase retrieved images provided similar or improved detection for all disc sizes except for the disk diameters of 2 mm and 1 mm for the 50 G-50 A phantom and 3 mm and 0.5 mm for the 70 G-30 A phantom. This study demonstrated the potential of utilizing a high energy phase sensitive x-ray imaging system to improve lesion detection and reduce radiation dose when imaging breast tissues with varying glandular compositions.


Beliefs and Barriers to COVID-19 Vaccine Acceptance in Three Countries with Different Human Development Index (HDI) Scores: A Comparative Study.
As vaccination is a cornerstone strategy to prevent the spread of COVID-19, this study assessed and compared beliefs about and barriers to COVID-19 vaccination among the population of three countries with different Human Development Index (HDI) scores: Saudi Arabia (very high), India (medium), and Sudan (low). A web-based, self-administered structured questionnaire was employed to collect data from the three countries. The questionnaire contained three sections that measured sociodemographic characteristics, participants' beliefs about and attitudes toward COVID-19 vaccines, barriers to receiving COVID-19 vaccines, and scenarios in which there is a possibility to take a COVID-19 vaccine. Multinomial logistic regression was used to determine whether there was an association between the country of the participant and their beliefs about COVID-19 vaccines. 972 responses were collected. The study participants from India were more likely to believe in the safety and efficacy of vaccines than those from Saudi Arabia or Sudan. Consequently, they reported more willingness to get vaccinated to avoid complications from COVID-19. Regarding barriers to COVID-19 vaccination, concerns about adverse effects and ineffectiveness of vaccines were more common among Saudi participants, while concerns about conspiracy were more common among Sudanese participants. COVID-19 vaccine acceptance was higher in countries with a very high to medium Human Development Index, indicating greater belief in the safety and efficacy of COVID-19 vaccines.


Depressive Symptoms and Sleep Disturbance in Female Nurses with Atopic Dermatitis: The Korea Nurses' Health Study.
Although the prevalence of atopic dermatitis is high in nurses, there is a lack of research on the relationship between atopic dermatitis and depressive symptoms and sleep disturbance among female nurses. This study aimed to determine the effects of atopic dermatitis on depressive symptoms and sleep disturbance in female nurses. We analyzed the data of the Korea Nurses' Health Study, a large-scale prospective cohort study. A total of 20,613 female hospital nurses aged 20-45 years who participated in the Module 1 of Korea Nurses' Health Study between July 2013 and November 2014 were included. The chi-square test, t-test, and multivariate ordinal logistic regression analysis were conducted for statistical analysis. The prevalence of atopic dermatitis among female nurses was 11.6%. The levels of depressive symptoms and sleep disturbance were higher in nurses with atopic dermatitis than those without atopic dermatitis. Nurses with atopic dermatitis were 1.16 times more likely to have depressive symptoms and 1.35 times more likely to have sleep disturbance than those without atopic dermatitis after adjusting for confounding variables. The results of this study suggest that additional support should be considered for nurses with atopic dermatitis to improve the occupational environment for managing and preventing the exacerbation of symptoms.


Altruism, incentives, and organ donation: attitudes of the transplant community.
This study investigated the attitudes of the transplant community toward the current policy of altruistic organ donation and 6 alternative policies offering incentives to the donor family. Two hundred forty-nine transplant surgeons, 143 transplant coordinators, and 134 critical-care nurses rated the moral appropriateness and success of the current policy of altruistic donation, rated the moral appropriateness of the alternative policies, judged whether donation would increase or decrease under each alternative policy, and decided whether each alternative policy should be put into effect. All 3 professions believed the current policy of altruistic organ donation to be morally appropriate and most of the alternative policies to be morally appropriate or morally neutral. All 3 professions believed the current policy to be at best only moderately successful and judged most or all of the alternative policies to be likely to increase donation. All 3 professions favored implementing a policy offering donor recognition; approximately one half of the surgeons and one half of the coordinators also advocated implementing a policy offering 1500 US dollars toward funeral expenses. In all 3 professions, respondents' decisions to implement the alternative policies were more frequently related to those policies' moral appropriateness than to their likelihood of increasing organ donation. Specific incentives varied in their acceptability to the transplant community. Attitudes of the transplant community toward incentives were not in accord with published criticisms of incentives.


Vascular endothelial growth factor transgenic mice exhibit reduced male fertility and placental rejection.
Recent evidence points to the involvement of vascular endothelial growth factor (VEGF) in mammalian reproductive physiology. Transgenic mice expressing VEGF (121 isoform) under the control of the polyepithelial mucin-1 (muc-1) promoter showed a reduction in male fertility due to impaired spermiogenesis, and aberrant placentation leading to preferential rejection of male embryos. A skew in the sex ratio of the litters was seen (three females to two males), independently of whether the transgene was carried by the male or female parent. In-situ hybridization permitted distinction of expression of the human VEGF transgene from endogenous mouse VEGF, and confirmed expression of the transgene in a wide range of epithelial tissues. Expression of the transgene in spermatocytes and in the embryonic portion of placenta is thought to be responsible for the reduced fertility and embryonic resorptions respectively. Males showed either complete sperm maturation arrest or various gradations of partial fertility. Abnormally high or low VEGF in human semen has been reported to be correlated with a lack of pregnancy success following IVF. The muc1-VEGF (121 isoform) transgenic mouse provides an animal model with which to further study this VEGF-induced pathology.


A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress.
The p75 neurotrophin receptor (p75(NTR)) mediates the death of specific populations of neurons during the development of the nervous system or after cellular injury. The receptor has also been implicated as a contributor to neurodegeneration caused by numerous pathological conditions. Because many of these conditions are associated with increases in reactive oxygen species, we investigated whether p75(NTR) has a role in neurodegeneration in response to oxidative stress. Here we demonstrate that p75(NTR) signaling is activated by 4-hydroxynonenal (HNE), a lipid peroxidation product generated naturally during oxidative stress. Exposure of sympathetic neurons to HNE resulted in neurite degeneration and apoptosis. However, these effects were reduced markedly in neurons from p75(NTR-/-) mice. The neurodegenerative effects of HNE were not associated with production of neurotrophins and were unaffected by pretreatment with a receptor-blocking antibody, suggesting that oxidative stress activates p75(NTR) via a ligand-independent mechanism. Previous studies have established that proteolysis of p75(NTR) by the metalloprotease TNFα-converting enzyme and γ-secretase is necessary for p75(NTR)-mediated apoptotic signaling. Exposure of sympathetic neurons to HNE resulted in metalloprotease- and γ-secretase-dependent cleavage of p75(NTR). Pharmacological blockade of p75(NTR) proteolysis protected sympathetic neurons from HNE-induced neurite degeneration and apoptosis, suggesting that cleavage of p75(NTR) is necessary for oxidant-induced neurodegeneration. In vivo, p75(NTR-/-) mice exhibited resistance to axonal degeneration associated with oxidative injury following administration of the neurotoxin 6-hydroxydopamine. Together, these data suggest a novel mechanism linking oxidative stress to ligand-independent cleavage of p75(NTR), resulting in axonal fragmentation and neuronal death.


Do beta-amyloid (Abeta) deposits in patients with Alzheimer's disease and Down's syndrome grow according to the log-normal model?
The size frequency distributions of diffuse, primitive and classic beta-amyloid (Abeta) deposits were studied in single sections of cortical tissue from patients with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those predicted by the log-normal model. In a sample of brain regions, these size distributions were compared with those obtained by serial reconstruction through the tissue and the data used to adjust the size distributions obtained in single sections. The adjusted size distributions of the diffuse, primitive and classic deposits deviated significantly from a log-normal model in AD and DS, the greatest deviations from the model being observed in AD. More Abeta deposits were observed close to the mean and fewer in the larger size classes than predicted by the model. Hence, the growth of Abeta deposits in AD and DS does not strictly follow the log-normal model, deposits growing to within a more restricted size range than predicted. However, Abeta deposits grow to a larger size in DS compared with AD which may reflect differences in the mechanism of Abeta formation.


Transarterial embolization for cervical hemangioma associated with Kasabach-merritt syndrome.
A 2-month-old girl presented with cervical hemangioma associated with Kasabach-Merritt syndrome. The patient had previously undergone systemic administration of corticosteroids (prednisolone 2 mg/kg/day) and radiotherapy (0.5 Gy × 5 times), which temporarily increased the platelet count, but the effects were short-lived and thrombocytopenia gradually worsened again despite increased dosage of prednisolone to 5 mg/kg/day. Computed tomography and magnetic resonance imaging revealed a hemangioma in the left retroauricular-cervical region with a well-enhanced, ill-defined margin and bony structure involvement. Diagnostic and therapeutic angiography were carried out through the femoral route under general anesthesia. Polyvinyl alcohol particles (250-350 µm) suspended in contrast medium were slowly injected and a fibered coil was finally placed in the proximal portion of the arterial feeder. Angiography after embolization revealed a marked reduction in the tumor stain. Platelet count rapidly increased and reached the normal range on postembolization day 7. Tumor tension decreased on the day after the procedure and tumor size gradually decreased. The patient was discharged with oral corticosteroid therapy at 6 months postembolization. Corticosteroid dose was gradually decreased and coagulation parameters were normal at 1 year postembolization.


Some Effects of Supplemental Pilates Training on the Posture, Strength, and Flexibility of Dancers 17 to 22 Years of Age.
Proper alignment in dancers is a pre-requisite for achieving aesthetic line and form and for efficient execution of movement. Pelvic alignment is a common deficit in dancers that results in faulty technique and impaired performance. Dancers must be able to obtain their personal neutral alignment to avoid injury and achieve ease of execution. This study was designed to examine the effects, qualitatively and quantitatively, of Pilates training on pelvic alignment, strength, and flexibility in dancers. Twenty female dancers, 17 to 22 years of age, participated in a screening that consisted of an AlignaBod posture screen, upper abdominal manual muscle test, double leg lower test, straight leg raise test, and modified Thomas test. Participants were screened, engaged in dance classes for 14 weeks without Pilates, and screened a second time. They then attended a 2-hour pelvic alignment workshop followed by two weekly Pilates classes, one mat and one apparatus, for 14 weeks. The study concluded with a final screening and collection of qualitative data regarding participant perceptions of their experience. Analysis demonstrated a decrease in the number of postural misalignments with Pilates intervention compared to no significant change in total misalignments when taking dance classes only. The prevalence of forward head posture, knee hyperextension, and foot-ankle pronation or supination all decreased significantly. After participating in the Pilates intervention, the prevalence of iliotibial band and hamstring inflexibility decreased and lower abdominal muscle strength improved significantly. All participants reported they felt that Pilates improved their core stability, pelvic alignment, strength, and body awareness. This study suggests that Pilates, when added to dance training, can improve postural alignment, flexibility, and abdominal strength in dancers. Additionally, it is well tolerated by dancers, making it a potentially valuable cross-training tool.


Combined corticosteroid and longacting beta-agonist in one inhaler for chronic obstructive pulmonary disease.
Long-acting beta-agonists and inhaled corticosteroids have been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. However, they have only been available until recently via separate administration. They have been developed in order to facilitate adherence to medication regimens, and to improve efficacy. To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations in the treatment of adults with chronic obstructive pulmonary disease. We searched the Cochrane Airways Group chronic obstructive pulmonary disease (COPD) trials register (March 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), LILACS (all years to March 2003) and reference lists of articles. We also contacted manufacturers and researchers in the field. Studies were included if they were randomised, with adequate blinding procedures in place. Studies could compare a combined inhaled corticosteroids and long-acting beta-agonist preparation with either component preparation or placebo. Studies comparing different members of each class of combined therapies were included Two reviewers independently assessed trial quality and extracted data. Four randomised trials with 2986 participants were included. Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were studied in the trials. No meta-analysis on clinical outcomes was possible due to different outcome assessment across studies. All studies demonstrated a reduction in exacerbation rates versus placebo. Budesonide/formoterol was more effective than formoterol in reducing exacerbations in one study from 1.84 to 1.42 exacerbations per year. Fluticasone/salmeterol did not significantly reduce exacerbations compared with either of its component treatments. Fluticasone/salmeterol led to better quality of life compared with placebo (two studies), although there were conflicting results when compared with inhaled corticosteroid alone (two studies). There was no significant difference between fluticasone/salmeterol and long-acting beta-agonist (two studies). Budesonide/formoterol led to statistically significant differences in quality of life compared with placebo, but not when compared with component inhaled corticosteroid or beta-agonist (one study). For the primary outcome of exacerbations, budesonide/formoterol had a modest advantage over a component medication, formoterol, in a single trial, but fluticasone/salmeterol did not result in a significant reduction in exacerbations compared to either of its components. The combination of steroids and long-acting beta-agonist in one inhaler was effective in improving symptoms compared with placebo and on certain clinical outcomes compared with one of the individual components alone. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, including the assessment of the comparative effects with separate administration of the two drugs in double-dummy trials.


Effect of short-duration hyperventilation during endotracheal suctioning on intracranial pressure in severe head-injured adults.
A repeated measures randomized within-group design was used to determine the effectiveness of controlled short-duration hyperventilation (HV) in blunting the increase of intracranial pressure (ICP) during endotracheal suctioning (ETS). A multimodal continuous real-time computerized data acquisition procedure was used to compare the effects of two HV ETS protocols on ICP, arterial pressure, cerebral perfusion pressure (CPP), heart rate, and arterial oxygen saturation in severe head-injured adult patients. The results indicated that short-duration HV for 1 minute, which decreases the PaCO2, reduced ETS-induced elevations in ICP while maintaining CPP. However, it is not clear whether short-duration HV is neuroprotective, particularly in ischemic regions of the brain. Therefore, before a change in practice is implemented on the use of short-duration HV as a prophylactic treatment against ETS-induced elevations in ICP, additional questions on cerebral oxygen delivery and uptake need to be answered.


Risk factors of road traffic accidents in Rural and Urban areas of indonesia based on the national survey of year 2018.
Indonesia has a large population with a large number of motorised vehicles, so it cannot be separated from traffic accidents. This study aimed to determine and analyse the advanced level risk factors for road traffic accidents (RTA) in rural and urban areas based on data from the Basic Health Research 2018 (Riskesdas). This study used Riskesdas data sourced from the National Institute of Health Research and Development, Ministry of Health, Indonesia, which was collected from 34 provinces in Indonesia using a cross-sectional method. The statistical data consisted of 59,423 respondents aged over 15 years old, who had experienced a road traffic injury and lived in rural or urban areas. The data variables analysis was socio-demographic, lifestyle, smoking status, alcohol consumption, mental disorders, nutritional status and use of helmets on motorcycle riders and passengers. Multivariate logistic regression was used to analyse the most dominant risk factors related to RTA in rural and urban areas. The prevalence of RTA in urban areas was 34.1%, while in rural areas was 28.2%. The factors related to traffic accidents in respondents from urban areas (P < 0.005) were sex (1.342 [1.217-1.480]), age (1.111 [1.067-1.156]) and use of helmets on motorcycle riders and passengers (0.662 [0.566-0.771]). Meanwhile, risk factors for respondents from rural areas (P < 0.005) were mental disorders (0.842 [0.743-0.955]), age (1.095 [1.040-1.154]) and use of helmets on motorcycle riders and passengers (0.682 [0.585-0.796]). We found that the prevalence of RTA in urban areas was higher than in rural areas. The dominant risk factors related to RTA in Indonesia were age, sex, mental disorders and the use of helmets on motorcycle riders and passengers. This finding supports the importance of road safety education and the prevention of RTA needs to be done both in urban and rural areas.


The cost-effectiveness of computer-assisted anticoagulant dosage: results from the European Action on Anticoagulation (EAA) multicentre study.
Increased demand for oral anticoagulation has resulted in wider adoption of computer-assisted dosing in anticoagulant clinics. An economic evaluation has been performed to investigate the cost-effectiveness of computer-assisted dosing in comparison with manual dosing in patients on oral anticoagulant therapy. A trial-based cost-effectiveness analysis was conducted as part of the EAA randomized study of computer-assisted dosage vs. manual dosing. The 4.5-year multinational trial was conducted in 32 centres with 13 219 anticoagulation patients randomized to manual or computer-assisted dosage. The main outcome measures were total health care costs, clinical event rates and cost-saving per clinical event prevented by computer dosing compared with manual dosing. Mean dosing costs per patient were lower (difference: euro47) for computer-assisted dosing, but with little difference in clinical event costs. Total overall costs were euro51 lower in the computer-assisted dosing arm. There were a larger number of clinical events in the manual dosing arm. The overall difference between trial arms was not significant (difference in clinical events, -0.003; 95% CI, -0.010-0.004) but there was a significant reduction in events with DVT/PE, suggesting computer-assisted dosage with the two study programs (dawn ac or parma 5) was at least as effective clinically as manual dosage. The cost-effectiveness analysis indicated that computer-assisted dosing is less costly than manual dosing. Results indicate that computer-assisted dosage with the two programs (dawn ac and parma 5) is cheaper than manual dosage and is at least as effective clinically, indicating that investment in this technology represents value for money.


Factors affecting the accuracy of genomic selection for growth and wood quality traits in an advanced-breeding population of black spruce (Picea mariana).
Genomic selection (GS) uses information from genomic signatures consisting of thousands of genetic markers to predict complex traits. As such, GS represents a promising approach to accelerate tree breeding, which is especially relevant for the genetic improvement of boreal conifers characterized by long breeding cycles. In the present study, we tested GS in an advanced-breeding population of the boreal black spruce (Picea mariana [Mill.] BSP) for growth and wood quality traits, and concurrently examined factors affecting GS model accuracy. The study relied on 734 25-year-old trees belonging to 34 full-sib families derived from 27 parents and that were established on two contrasting sites. Genomic profiles were obtained from 4993 Single Nucleotide Polymorphisms (SNPs) representative of as many gene loci distributed among the 12 linkage groups common to spruce. GS models were obtained for four growth and wood traits. Validation using independent sets of trees showed that GS model accuracy was high, related to trait heritability and equivalent to that of conventional pedigree-based models. In forward selection, gains per unit of time were three times higher with the GS approach than with conventional selection. In addition, models were also accurate across sites, indicating little genotype-by-environment interaction in the area investigated. Using information from half-sibs instead of full-sibs led to a significant reduction in model accuracy, indicating that the inclusion of relatedness in the model contributed to its higher accuracies. About 500 to 1000 markers were sufficient to obtain GS model accuracy almost equivalent to that obtained with all markers, whether they were well spread across the genome or from a single linkage group, further confirming the implication of relatedness and potential long-range linkage disequilibrium (LD) in the high accuracy estimates obtained. Only slightly higher model accuracy was obtained when using marker subsets that were identified to carry large effects, indicating a minor role for short-range LD in this population. This study supports the integration of GS models in advanced-generation tree breeding programs, given that high genomic prediction accuracy was obtained with a relatively small number of markers due to high relatedness and family structure in the population. In boreal spruce breeding programs and similar ones with long breeding cycles, much larger gain per unit of time can be obtained from genomic selection at an early age than by the conventional approach. GS thus appears highly profitable, especially in the context of forward selection in species which are amenable to mass vegetative propagation of selected stock, such as spruces.


Combined use of cyclosporine A and methotrexate in refractory polymyositis.
Polymyositis is an inflammatory muscle disease with unknown cause that is characterized by progressive weakness of the proximal muscles. Limited information is available concerning the effectiveness of the combination therapy with cyclosporine A and methotrexate in reducing myositis activity. We describe here a female patient with polymyositis who showed resistance to pulse corticosteroid therapy. Neither the combination of azathioprine (100 mg/day) nor methotrexate (10 mg/week) with corticosteroids decreased the value of creatine phosphokinase. Normalization of the creatine phosphokinase level as well as improvement of muscle strength was obtained only when low-dose cyclosporine A (3 mg/kg/day) was combined with methotrexate.


Polarimetric infrared imaging simulation of a synthetic sea surface with Mie scattering.
A novel method to simulate the polarimetric infrared imaging of a synthetic sea surface with atmospheric Mie scattering effects is presented. The infrared emission, multiple reflections, and infrared polarization of the sea surface and the Mie scattering of aerosols are all included for the first time. At first, a new approach to retrieving the radiative characteristics of a wind-roughened sea surface is introduced. A two-scale method of sea surface realization and the inverse ray tracing of light transfer calculation are combined and executed simultaneously, decreasing the consumption of time and memory dramatically. Then the scattering process that the infrared light emits from the sea surface and propagates in the aerosol particles is simulated with a polarized light Monte Carlo model. Transformations of the polarization state of the light are calculated with the Mie theory. Finally, the polarimetric infrared images of the sea surface of different environmental conditions and detection parameters are generated based on the scattered light detected by the infrared imaging polarimeter. The results of simulation examples show that our polarimetric infrared imaging simulation can be applied to predict the infrared polarization characteristics of the sea surface, model the oceanic scene, and guide the detection in the oceanic environment.


Combined treatment with nicotinamide and desferrioxamine prevents islet allograft destruction in NOD mice.
Nonobese diabetic (NOD) mice get spontaneous diabetes with clinical and pathological manifestations similar to those seen in human type I diabetes. NOD mice will destroy transplants of treated allogeneic islet tissue by a recurrence of the disease process that destroyed the original islet tissue. This may be prevented by treatment of the animals with combined desferrioxamine and nicotinamide. Transplanted animals become normoglycemic and remain so for the duration of the treatment. This suggests that oxygen-derived free radicals may be involved in islet damage in spontaneous diabetes.


Diagnostic efficacy of a low-dose 32-projection SPECT 99mTc-sestamibi myocardial perfusion imaging protocol in routine practice.
99mTc-labeled tracers can provide better imaging quality than does TI for myocardial perfusion imaging (MPI). Nevertheless, a large study showed no significant difference in diagnostic efficacy, implying that image quality, though not optimal, may be still adequate for reliable interpretation. We thus proposed a suboptimal low-dose 32-projection single-photon emission computed tomography (SPECT) 99mTc-sestamibi (99mTc-methoxyisobutylisonitrile) MPI protocol and evaluated its diagnostic efficacy. A total of 1007 patients undergoing the proposed rest-stress MPI protocol were included in the study for analysis. Among them, 218 had coronary angiography, which was used as the 'gold standard' for evaluating sensitivity and specificity. The normalcy rate was obtained from 47 patients with a low cardiovascular risk. The injected dosage for 99mTc-methoxyisobutylisonitrile resting and dipyridamole stress imaging is 185 and 555 MBq, respectively, with an interval of about 2 h between the two injections. Most of the patients completed the whole MPI within 3 h. Using this protocol, the sensitivity and specificity of the 218 patients with subsequent coronary angiography for determining coronary artery disease were 95 and 63%, respectively. The normalcy rate was 87%. Both the rest and stress images were adequate for confident interpretation. The proposed low-dose 32-projection SPECT protocol has a diagnostic efficacy comparable with that reported in the literature, most of which used a higher dose and 64-projection SPECT, with additional benefits of lower radiation exposure, lower cost, and shorter study time.


Suppression of Plant Immune Responses by the Pseudomonas savastanoi pv. savastanoi NCPPB 3335 Type III Effector Tyrosine Phosphatases HopAO1 and HopAO2.
The effector repertoire of the olive pathogen P. savastanoi pv. savastanoi NCPPB 3335 includes two members of the HopAO effector family, one of the most diverse T3E families of the P. syringae complex. The study described here explores the phylogeny of these dissimilar members, HopAO1 and HopAO2, among the complex and reveals their activities as immune defense suppressors. Although HopAO1 is predominantly encoded by phylogroup 3 strains isolated from woody organs of woody hosts, both HopAO1 and HopAO2 are phylogenetically clustered according to the woody/herbaceous nature of their host of isolation, suggesting host specialization of the HopAO family across the P. syringae complex. HopAO1 and HopAO2 translocate into plant cells and show hrpL-dependent expression, which allows their classification as actively deployed type III effectors. Our data also show that HopAO1 and HopAO2 possess phosphatase activity, a hallmark of the members of this family. Both of them exert an inhibitory effect on early plant defense responses, such as ROS production and callose deposition, and are able to suppress ETI responses induced by the effectorless polymutant of P. syringae pv. tomato DC3000 (DC3000D28E) in Nicotiana. Moreover, we demonstrate that a ΔhopAO1 mutant of P. savastanoi NCPBB 3335 exhibits a reduced fitness and virulence in olive plants, which supports the relevance of this effector during the interaction of this strain with its host plants. This work contributes to the field with the first report regarding functional analysis of HopAO homologs encoded by P. syringae or P. savastanoi strains isolated from woody hosts.


[Craniocerebral injuries as a risk factor in the occurrence of epilepsy].
Results of experimental investigations of the convulsive readiness and risk factors of traumatic epilepsy occurrence using the mild craniocerebral trauma (mCCT) model are adduced. The dynamics of convulsive readiness of traumatic origin was studied up in experimental animals (rats) in the late period after (mCCT), and also the stimulating influences of an excessive mechanical loadings, chronic alcoholization and deprivation as a promotions of increased risk for the persistent pathological status occurrence. Results of investigations witnesses that the combined risk factors action makes (mCCT) sufficient etiological factor for traumatic epilepsy.


Recognizing Early Regulation Disorders in Pediatric Care: The For Healthy Offspring Project.
BACKGROUND Regulation disorders are already apparent in infancy. The For Healthy Offspring Project was the first Hungarian study aimed at building an effective model for screening and examining the prevalence and complex (medical and psychosocial) background of classic behavior regulation disorders (excessive crying, feeding, and sleep problems) in infancy. MATERIAL AND METHODS Data were collected from families of 0- to 3-year-old children in a pediatric hospital and its neighboring areas through questionnaires, medical examinations, and individual and small-group consultations. RESULTS In the questionnaire study about their children's behavior (n=1133), 15% of mothers reported excessive crying, 16% reported feeding problems, and 10% reported sleep problems. In a subsample (n=619) in which medical examinations were also conducted, the prevalence of medical diagnoses was 15.0% for excessive crying, 15.2% for sleep disorders, 10.3% for breastfeeding difficulties, and 14.8% for feeding disorders. Children who were referred to the screening program (n=183) had significantly more behavior regulation disorders than the other children in our study. Regulation disorders were found to be comorbid with other health conditions in some cases. CONCLUSIONS We developed a complex model to screen for regulatory problems in early childhood. This study adds more information about the relationship between regulation problems and other health conditions. The general incidence (5-15%) of early childhood regulation disorders in other countries is likely similar to that found in Hungary. In order to effectively recognize early regulation disorders, diagnostic instruments widely used in the international field should be adapted in general Hungarian pediatric care.


Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat.
In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG), was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine deaminase immunostaining was subsequently performed for the tuberomammillary nucleus (TMN) in order to investigate projections from the TMN to the two brainstem monoaminergic nuclei. Following rostral DR injections, the majority of retrogradely labeled cells were located in the dorsomedial and ventrolateral subdivisions of the TMN. At middle DR levels, midline injections resulted in labeling mainly in the ventrolateral subdivision, whereas lateral wing injections produced labeling mostly in ventral and caudal TMN subdivisions. When injections were made in the caudal DR, only a few cells were observed along the rostro-caudal extent of the TMN. On the other hand, following rostral LC injections, labeled neurons were observed mainly in ventrolateral and ventral subdivisions of TMN. For principal LC injections, labeled cells were observed mostly in ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at caudal pole of LC, only a few cells were located along the rostro-caudal extent of the TMN. In the second series of experiments, an iontophoretic injection of fluorogold (FG) into the DR was paired with a pressure injection of WG into the LC to investigate the collateral distribution of TMN axonal fibers to DR and LC. Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN subdivisions. The present study indicated that there exists a robust projection from the TMN to the DR or the LC and that some TMN neurons have axon collaterals projecting to both DR and LC. The TMN neurons with such axon collaterals might provide simultaneous, possibly more efficient, way of controlling the brainstem monoaminergic nuclei, thus influencing various sleep and arousal states of the animal.


The Neglected Marine Fungi, Sensu stricto, and Their Isolation for Natural Products' Discovery.
Despite the rapid development of molecular techniques relevant for natural product research, culture isolates remain the primary source from which natural products chemists discover and obtain new molecules from microbial sources. Techniques for obtaining and identifying microbial isolates (such as filamentous fungi) are thus of crucial importance for a successful natural products' discovery program. This review is presented as a "best-practices guide" to the collection and isolation of marine fungi for natural products research. Many of these practices are proven techniques used by mycologists for the isolation of a broad diversity of fungi, while others, such as the construction of marine baiting stations and the collection and processing of sea foam using dilution to extinction plating techniques, are methodological adaptations for specialized use in marine/aquatic environments. To this day, marine fungi, Sensu stricto, remain one of the few underexplored resources of natural products. Cultivability is one of the main limitations hindering the discovery of natural products from marine fungi. Through encouraged collaboration with marine mycologists and the sharing of historically proven mycological practices for the isolation of marine fungi, our goal is to provide natural products chemists with the necessary tools to explore this resource in-depth and discover new and potentially novel natural products.


Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats.
Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein-ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, alpha-smooth muscle actin and PDGFR-beta expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension.


[Treatment of peptic ulcer with jian-wei yu-wang tablets].
This article reports the results of second stage clinical trial on the treatment of peptic ulcer with jian-wei yu-yang (JWYY) tablets in comparison with a control group treated with ranitidine. The results showed that the cure rate for JWYY tablet group was 62.4% and its effective rate was 93. 8% in 354 cases, whereas the cure rate of the control group was 50.7% and its effective rate was 86. 4% in 140 cases. The differences between these two groups were highly significant (P less than 0.01). Based on syndrome differentiation, optimal effect was reached in treating liver stagnation and spleen deficiency syndrome and disharmony of liver and stomach syndrome. After one year follow up studies of the therapeutic effect, the recurrence rate of the JWYY tablet group was 17.7%, while that of the ranitidine group was 54.1%. In addition, JWYY tablet had no side-effects. These data indicated that JWYY tablets were a more effective therapeutic remedy for peptic ulcer.


Factors affecting open-set word recognition in adults with cochlear implants.
A great deal of variability exists in the speech-recognition abilities of postlingually deaf adult cochlear implant (CI) recipients. A number of previous studies have shown that duration of deafness is a primary factor affecting CI outcomes; however, there is little agreement regarding other factors that may affect performance. The objective of the present study was to determine the source of variability in CI outcomes by examining three main factors, biographic/audiologic information, electrode position within the cochlea, and cognitive abilities in a group of newly implanted CI recipients. Participants were 114 postlingually deaf adults with either the Cochlear or Advanced Bionics CI systems. Biographic/audiologic information, aided sentence-recognition scores, a high resolution temporal bone CT scan and cognitive measures were obtained before implantation. Monosyllabic word recognition scores were obtained during numerous test intervals from 2 weeks to 2 years after initial activation of the CI. Electrode position within the cochlea was determined by three-dimensional reconstruction of pre- and postimplant CT scans. Participants' word scores over 2 years were fit with a logistic curve to predict word score as a function of time and to highlight 4-word recognition metrics (CNC initial score, CNC final score, rise time to 90% of CNC final score, and CNC difference score). Participants were divided into six outcome groups based on the percentile ranking of their CNC final score, that is, participants in the bottom 10% were in group 1; those in the top 10% were in group 6. Across outcome groups, significant relationships from low to high performance were identified. Biographic/audiologic factors of age at implantation, duration of hearing loss, duration of hearing aid use, and duration of severe-to-profound hearing loss were significantly and inversely related to performance as were frequency modulated tone, sound-field threshold levels obtained with the CI. That is, the higher-performing outcome groups were younger in age at the time of implantation, had shorter duration of severe-to-profound hearing loss, and had lower CI sound-field threshold levels. Significant inverse relationships across outcome groups were also observed for electrode position, specifically the percentage of electrodes in scala vestibuli as opposed to scala tympani and depth of insertion of the electrode array. In addition, positioning of electrode arrays closer to the modiolar wall was positively correlated with outcome. Cognitive ability was significantly and positively related to outcome; however, age at implantation and cognition were highly correlated. After controlling for age, cognition was no longer a factor affecting outcomes. There are a number of factors that limit CI outcomes. They can act singularly or collectively to restrict an individual's performance and to varying degrees. The highest performing CI recipients are those with the least number of limiting factors. Knowledge of when and how these factors affect performance can favorably influence counseling, device fitting, and rehabilitation for individual patients and can contribute to improved device design and application.


Arthritis gene therapy and its tortuous path into the clinic.
Arthritis is a disease of joints. The biology of joints makes them very difficult targets for drug delivery in a manner that is specific and selective. This is especially true for proteinaceous drugs ("biologics"). Gene transfer is the only technology that can solve the delivery problem in a clinically reasonable fashion. There is an abundance of preclinical data confirming that genes can be efficiently transferred to tissues within joints by intra-articular injection using a variety of different vectors in conjunction with ex vivo and in vivo strategies. Using the appropriate gene transfer technologies, long-term, intra-articular expression of anti-arthritic transgenes at therapeutic concentrations can be achieved. Numerous studies confirm that gene therapy is effective in treating experimental models of rheumatoid arthritis (RA) and osteoarthritis (OA) in the laboratory. A limited number of clinical trials have been completed, which confirm safety and feasibility but only 3 protocols have reached phase II; as yet, there is no unambiguous evidence of efficacy in human disease. Only 2 clinical trials are presently underway, both phase II studies using allogeneic chondrocytes expressing transforming growth factor-β1 for the treatment of OA. Phase I studies using adeno-associated virus to deliver interleukin-1Ra in OA and interferon-β in RA are going through the regulatory process. It is to be hoped that the recent successes in treating rare, Mendelian diseases by gene therapy will lead to accelerated development of genetic treatments for common, non-Mendelian diseases, such as arthritis.


Transient cleavage kinetics of the Eco RI restriction endonuclease measured in a pulsed quench-flow apparatus: enzyme concentration-dependent activity change.
We report measurements of the cleavage rate of pBR 322 plasmid DNA by the restriction endonuclease Eco RI as a function of enzyme and DNA concentration. The reaction, which at high excess of enzyme over DNA occurs between 0.2 and 5 seconds, was studied by the means of a microprocessor controlled pulsed quench-flow apparatus. Enzyme concentrations were between 1 and 100 nM with DNA concentrations being 3 to 6 nM (specific Eco RI sites). The catalytic constants for cleavage of the first and second phosphodiester bonds as measured at high enzyme concentration both have the same value of 0.35 sec-1 and 21 degrees C. At enzyme concentrations comparable to or less than DNA concentration, the rate of the first cleavage is proportional to enzyme concentration, while the second step is independent of concentration. At approx. 10 nM Eco RI endonuclease concentration, a rate increase shows up in both the first and the second cleavage. We suggest that this increase is due to the tetramerization reported by Modrich & Zabel1, which occurs in this concentration range.


Office diagnostic procedures.
Tympanocentesis, punch biopsy of the skin, bone marrow aspiration and biopsy, and temporal artery biopsy are procedures discussed in this article. They are principally diagnostic procedures used in the evaluation of skin and serious systemic disease.


[Single balloon enteroscopy in the management of small bowel pathology. Experience of the Small Bowel Unit - British American Hospital from December 2012 to December 2018].
Objetive: To describe our experience with single balloon enteroscopy in the management of small bowel disease in British American Hospital, Lima - Perú. Descriptive and prospective study. We include all patients that come to perform a single balloon enteroscopy in small bowel unit of British American Hospital within December 2012 to December 2018. We performed 80 procedures of single balloon enteroscopy, 49 were done by oral approach, 31 by rectal approach. Mean age were 60.78 years-old (20 - 88 years). 48 patients (60%) were male. The mean insertion time for oral approach was 80 minutes (55-141 minutes), and for rectal approach was 110 minutes (55-180 minutes). The main indication for single balloon enteroscopy was obscure gastrointestinal bleeding. 6 enteroscopies were performed in patients with altered surgical anatomy (7.5%). 70 of 80 procedures (87.5%) were performed with gastroenterology-administered sedation, using midazolam, pethidine and propofol, without any respiratory or hemodinamic complication. Diagnostics achieved by single balloon enteroscopy were small bowel angiodysplasias (20%), yeyuno ileal ulcers (17.5%) and small bowel neoplasia (7.5%). Paralytic ileus was the most common complication of single balloon enteroscopy, 2 cases, and both cases were associated after no using carbon dioxide insufflation during procedure. Obscure gastrointestinal bleeding was the main indication for single balloon enteroscopy. Diagnostics achieved by single balloon enteroscopy were small bowel angiodysplasias (20%), yeyuno ileal ulcers (17.5%) and small bowel neoplasia (7.5%). Paralytic ileus was the most common complication of single balloon enteroscopy, 2 cases, and both cases were associated after no using carbon dioxide insufflation during procedure.


Fetal oxidative stress, micronutrient deficiency and risk of retinopathy of prematurity: a nested case-control study.
We hypothesized that fetal oxidative stress and micronutrient deficiencies contribute to higher incidence of retinopathy of prematurity (ROP) in developing countries. In a nested case-control study, preterm infants (< 37 weeks, < 1700 g) were included at birth and followed until 40 weeks post-menstrual age (PMA). Maternal, cord, and neonatal serum/plasma samples at 40 weeks PMA were frozen. Samples of "cases" with ROP and gestational age (GA) and birth weight-matched "controls" with no ROP (in 1:4 ratio) were thawed and analyzed. MDA concentration in cord plasma. MDA in maternal and 40-week PMA plasma; copper, zinc, and vitamin A in maternal, cord, and 40-week PMA samples. Thirty-eight cases and 151 controls had a mean (SD) GA of 29.5 (1) and 29.9 (1) weeks respectively. Following were associated with ROP: higher MDA concentration in cord and 40-week PMA samples; lower copper and zinc in maternal serum; lower zinc and vitamin A in cord sample (all p < 0.05). MDA [adjusted OR (aOR) = 4.13 (95% CI 1.83-9.27)] and vitamin A [aOR = 0.09 (95% CI 0.02-0.4)] concentration in cord plasma and weight gain (g/kg/week) [aOR = 0.97 (0.95-0.99)] independently predicted ROP. Increased oxidative stress and deficiency of micronutrients from fetal life were associated with ROP. Clinical Trials Registry of India CTRI/REF/2014/12/008174. What is Known: • In developing countries, there is a higher incidence of retinopathy of prematurity (ROP), but micronutrient deficiencies have not been adequately investigated as risk factors. • Few observational studies have shown an association between ROP and postnatal increase in malondialdehyde (MDA) levels and deficiencies of antioxidant vitamins and minerals, but none in cord blood. What is New: • High MDA, low zinc, and low vitamin A levels in cord blood and low copper and zinc levels in maternal blood are associated with the development of ROP. • On multivariable analysis, high cord blood MDA and low cord blood vitamin A are independent predictors of ROP.


Euclidean distance matrix analysis of surgical changes in prepubertal craniofacial microsomia patients treated with an inverted L osteotomy.
Correction of craniofacial microsomia (CFM) presents several challenges concerning the modality of surgical intervention. The aim of this study was to assess early and late surgical outcome, by undertaking Euclidean distance matrix analysis (EDMA) of CFM patients exhibiting an unilateral mandibular deformity that was surgically corrected by an inverted L osteotomy and autogenous bone graft. Longitudinal study. Preoperative, approximately =1-year postoperative and approximately 3-year postoperative assessments of 14 consecutive children (mean age 9 years) with CFM. Posteroanterior cephalographs were scanned and five homologous mandibular landmarks were digitized in triplicate (< 1% digitization error). Average mandibular geometries, scaled to an equivalent size, were generated using a generalized rotational fit program (Procrustes superimposition) and subjected to EDMA. The mean pre- and both postoperative mandibular configurations differed statistically (p < .01). Early postoperative improvements in mandibular form were noted; increases in length arising in the treated mandibular body (approximately =19%) and ramus (approximately =13%). Comparing early and late postoperative configurations, a decrease of approximately =22% in the late postoperative mandibular body length was evident, but the ramus maintained steady vertical growth (approximately =7%). Comparing the preoperative and late postoperative configurations, the decrease observed in the mandibular body on the treated side was reduced to approximately =8% while the ramus maintained good growth (approximately =20%) on that side. Mandibular morphology is improved significantly in CFM patients surgically treated by an inverted L osteotomy, but relapse in the mandibular body is evident after approximately =3 years. Nevertheless, ramus growth proceeds well after the surgical reconstruction.


Molecular characterization of methicillin-resistant Staphylococcus aureus from a fatal case of necrotizing fasciitis in an extremely low-birth-weight infant.
Necrotizing fasciitis due to methicillin-resistant Staphylococcus aureus (MRSA) is an uncommon but life-threatening infection, and has mainly been reported as occurring in adults and the elderly. Recently, infant cases involving Panton-Valentine leukocidin (PVL)-positive community-acquired MRSA have been noted. Here, a case of fatal necrotizing fasciitis with sepsis and disseminated intravascular coagulation in an extremely low-birth-weight infant is described. The causative agent was the hospital-acquired MRSA New York/Japan clone carrying the spa variant gene and nine staphylococcal enterotoxin (SE) genes. These data suggest that a high-level combination of SEs and other virulence factors, but not PVL, could contribute to the pathogenesis of fatal necrotizing fasciitis.


Production of lentiviral vectors using novel, enzymatically produced, linear DNA.
The manufacture of large quantities of high-quality DNA is a major bottleneck in the production of viral vectors for gene therapy. Touchlight Genetics has developed a proprietary abiological technology that addresses the major issues in commercial DNA supply. The technology uses 'rolling-circle' amplification to produce large quantities of concatameric DNA that is then processed to create closed linear double-stranded DNA by enzymatic digestion. This novel form of DNA, Doggybone™ DNA (dbDNA™), is structurally distinct from plasmid DNA. Here we compare lentiviral vectors production from dbDNA™ and plasmid DNA. Lentiviral vectors were administered to neonatal mice via intracerebroventricular injection. Luciferase expression was quantified in conscious mice continually by whole-body bioluminescent imaging. We observed long-term luciferase expression using dbDNA™-derived vectors, which was comparable to plasmid-derived lentivirus vectors. Here we have demonstrated that functional lentiviral vectors can be produced using the novel dbDNA™ configuration for delivery in vitro and in vivo. Importantly, this could enable lentiviral vector packaging of complex DNA sequences that have previously been incompatible with bacterial propagation systems, as dbDNA™ technology could circumvent such restrictions through its phi29-based rolling-circle amplification.


Presentations of diarrhoea in Australian general practice.
The BEACH program, a continuous national study of general practice activity in Australia, gives us an overview of the consultations in general practice involving a patient presentation of diarrhoea. This provides a backdrop against which articles in this issue of the Australian Family Physician can be further considered.


N-Methylmelamines: Synthesis, Characterization, and Physical Properties.
N-Methylmelamines have recently gained importance as valuable compounds for manufacturing modified melamine formaldehyde resins and other polymer building blocks. A great advantage of these polymers is the reduction of the carcinogenic formaldehyde. Selecting the polymerization processes (e.g., substance polymerization, polymerization in solution) and controlling the polymerization reaction and properties of these novel materials requires knowledge of the properties of the individual melamine derivatives used as new building blocks. All possible permutations of N-methylmelamines were prepared, and reaction progress was monitored by GC/MS. 2,4,6-Tris(dimethylamino)-1,3,5-triazine was prepared to complete the series; this is, however, also a possible byproduct in various synthesis routes. The reaction conditions were optimized to obtain high yields of each derivative with the highest possible purity. The substances were characterized by NMR and IR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction. In addition, physical properties, such as solubility, melting points, and pKb values, were determined. The number of amino-, methylamino-, and dimethylamino groups has a significant effect on these properties. In summary, we found that by increasing the number of amino- and methylamino groups, solubility and pKb increase. With increasing number of amino groups, the compounds tend to form hydrogen bonds, and thus, the melting point shifts to higher temperature ranges where they start to decompose.


Design a compliance plan for the medical office.
The Affordable Care Act has mandated that all physician offices will need to have a compliance plan and compliance point of contact. Although the Office of Inspector General has not yet set the date, now is the time to get ready and design a compliance plan for your medical office. Fraud, waste, and abuse are at an all-time high. The government and taxpayers want to plug the holes where valuable healthcare dollars are being inappropriately used. Be proactive and take the time to design your compliance plan now. Read on to learn how to remove the question of "who, what, and I don't know" from your vocabulary when it comes to the topic of compliance!


Use of Twitter in Neurology: Boon or Bane?
Twitter is a free, open access social media platform that is widely used in medicine by physicians, scientists, and patients. It provides an opportunity for advocacy, education, and collaboration. However, it is likely not utilized to its full advantage by many disciplines in medicine, and pitfalls exist in its use. In particular, there has not been a review of Twitter use and its applications in the field of neurology. This review seeks to provide an understanding of the current use of Twitter in the field of neurology to assist neurologists in engaging with this potentially powerful application to support their work.


Nanocapsules improve indole-3-carbinol photostability and prolong its antinociceptive action in acute pain animal models.
This study aimed the development of nanocapsules (NCs) for oral indole-3-carbinol (I3C) administration and evaluation of antinociceptive potential of this compound in its two forms, free and nanoencapsulated, using acute pain models. NCs showed adequate physicochemical characteristics and protected the I3C against UVC radiation exposure. It was observed no chemical bond between I3C and polymer by FTIR. Besides, X-ray and DSC analysis suggested that I3C was molecularly dispersed in NCs. The dialysis bag technique showed that almost 100% of the compound was released from NCs at 360min. Mathematical modeling demonstrated that this release occurred in two rates, with an initial burst effect followed by a slower release of I3C. Regarding the in vivo analysis, time-response curve showed that both forms of I3C caused an inhibition in inflammatory phase of nociception induced by formalin and increased the latency response in hot plate test. Interestingly, NCs were able to prolong the I3C effect in both tests. Furthermore, in dose-response curve, only I3C in its nanoencapsulated form presented effect on inflammatory phase of the formalin test. In conclusion, NCs to I3C incorporation presented adequate nanometric characteristics and prolonged its antinociceptive action in acute pain models tested.


Clinical significance of endoleak detected on follow-up CT after endovascular repair of abdominal aortic aneurysm.
The purpose of this study was to evaluate the clinical significance of endoleaks detected on combined arterial and delayed contrast-enhanced follow-up CT examinations of patients who have undergone endovascular aneurysm repair of abdominal aortic aneurysm. One hundred forty-four patients underwent periodic follow-up CT examinations 12-72 months after abdominal aortic aneurysm repair. The CT protocol consisted of an unenhanced scan and contrast-enhanced scans in the arterial and 90-second delayed phases. The endoleaks detected on dual-phase CT scans were evaluated in association with the outcome (therapeutic intervention or endoleak resolution). The 144 patients underwent 728 CT examinations with a mean follow-up period of 35.5 +/- 14.5 months. Fifty endoleaks were detected in 50 (34.7%) of the patients. Eight endoleaks were detected in the arterial phase only, eight in the delayed phase only, and 34 in both phases. Intervention was performed to manage 16 endoleaks detected in both phases. CT showed that three endoleaks were stable (two in the arterial phase only and one in both phases) and that 31 had resolved completely (six in the arterial phase only, eight in the delayed phase only, and 17 in both phases). This finding represents a higher frequency of resolution of endoleaks detected in one phase only than in both phases (Fisher's exact test, p = 0.006). Endoleaks detected only in the delayed phase of CT had resolved spontaneously without intervention. Therefore, we can consider eliminating the delayed phase of acquisition to minimize radiation exposure.


N-telopeptide of type II collagen interacts with annexin V on human chondrocytes.
Type II collagen binds to chondrocytes through integrins and annexin V. While the potential integrin binding sites have been identified, it is unclear which domains bind to annexin V. Proteolytic fragments of collagen are known to modulate cell signaling pathways resulting in degradation of articular cartilage; it is unknown whether annexin V binds to the fragments. The focus of our study was to determine the binding of type II collagen and its fragments to chondrocytes using flow cytometry and fluorescence microscopy. The N-telopeptide binds to annexin V, whereas the C-telopeptide and triple helical peptides do not. These data suggest that the binding of the N-telopeptide of type II collagen is through annexin V, whereas binding of the C-telopeptide and the triple helical peptide to the surface of chondrocytes are potentially facilitated through other collagen receptors, such as integrins or cell-associated matrix proteins.


Deciphering the genetic basis of resistome and virulome diversity among multidrug-resistant Mycoplasma hominis.
Mycoplasma hominis, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of M. hominis isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a M. hominis isolate recovered from a pelvic abscess sample in China. Genomic DNA was extracted and sequenced using Illumina HiSeq X Ten platform. De novo assembly was performed and in silico analysis was accomplished by multiple bioinformatics tools. For phylogenomic analysis, publicly available M. hominis genomes were retrieved from NCBI GenBank database. Whole genome sequencing data showed that the genome size of M. hominis MH4246 was calculated as 679,746 bp, with 558 protein-coding sequences and a G + C content of 26.9%. M. hominis MH4246 is resistant to fluoroquinolones and macrolides, harboring mutations in the quinolone resistance-determining regions (QRDRs) (GyrA S153L, ParC S91I and ParE V417I) and 23S rRNA gene (G280A, C1500T, T1548C and T2218C). Multiple virulence determinants, such as tuf, hlyA, vaa, oppA, MHO_0730 and alr genes, were identified. Phylogenetic analysis showed that the closest relative of M. hominis MH4246 was the strain MH-1 recovered from China, which differed by 3490 SNPs. Overall, this study contributes to the comprehension of genomic characteristics, antimicrobial resistance patterns, and the mechanisms underlying the pathogenicity of this pathogen.


Protease-activated receptor 1 (PAR1) signalling desensitization is counteracted via PAR4 signalling in human platelets.
PARs (protease-activated receptors) 1 and 4 belong to the family of G-protein-coupled receptors which induce both G(α12/13) and G(αq) signalling. By applying the specific PAR1- and PAR4-activating hexapeptides, SFLLRN and AYPGKF respectively, we found that aggregation of isolated human platelets mediated via PAR1, but not via PAR4, is abolished upon homologous receptor activation in a concentration- and time-dependent fashion. This effect was not due to receptor internalization, but to a decrease in Ca²⁺ mobilization, PKC (protein kinase C) signalling and α-granule secretion, as well as to a complete lack of dense granule secretion. Interestingly, subthreshold PAR4 activation rapidly abrogated PAR1 signalling desensitization by differentially reconstituting these affected signalling events and functional responses, which was sufficient to re-establish aggregation. The lack of ADP release and P2Y₁₂ receptor-induced G(αi) signalling accounted for the loss of the aggregation response, as mimicking G(αi/z) signalling with 2-MeS-ADP (2-methylthioadenosine-5'-O-diphosphate) or epinephrine (adrenaline) could substitute for intermediate PAR4 activation. Finally, we found that the re-sensitization of PAR1 signalling-induced aggregation via PAR4 relied on PKC-mediated release of both ADP from dense granules and fibrinogen from α-granules. The present study elucidates further differences in human platelet PAR signalling regulation and provides evidence for a cross-talk in which PAR4 signalling counteracts mechanisms involved in PAR1 signalling down-regulation.


Towards detailed predictions of coastal ecosystem function under climate change.
The complex ways in which ongoing warming will restructure ecosystems remains poorly understood. A new simulation study in PLOS Biology suggests that expected changes in food resources for marine consumers will outpace the direct, pervasive effects of predicted +2.5°C warming.


Adrenergically stimulated fat utilization and ageing.
Ageing is associated with a diminished ability to use fat as a fuel during exercise. Also, middle-aged subjects have a blunted ability to mobilize fatty acids and to increase skeletal muscle fatty acid uptake and oxidation during intravenous beta-adrenergic stimulation, indicating that the sympathetic nervous system may play a role in the disturbed fat utilization. The blunted lipolytic response may be related to disturbances at the receptor level, eg a diminished number or agonist affinity of beta-adrenoceptors, or at the postreceptor level, eg a diminished activity of the hormone-sensitive lipase complex. As the rates of fatty acid availability are not limiting during exercise or beta-adrenergic stimulation in the elderly, the lowered skeletal muscle fat oxidation is probably related to an age-related decline in the capacity of skeletal muscle to oxidize fatty acids. Factors responsible for this decline may be a diminished content of oxidative enzymes, an increased glycolytic flux inhibiting fatty acid transport into the mitochondria, or a diminished (possibly beta-adrenergically-mediated) activation of fatty acid transport. It remains to be determined to what extent disturbances of fat metabolism may be related to the ageing process per se or whether they are secondary to age-related changes in body fat distribution and level of physical activity. Nevertheless, the impairments in sympathetically mediated lipolysis and fat oxidation may be of importance in the age-related increase in adiposity and insulin resistance and may thus be one of the links between ageing and increased prevalence of chronic diseases, such as obesity, type 2 diabetes mellitus, and cardiovascular disease.


Chronic elevation of calmodulin in the ventricles of transgenic mice increases the autonomous activity of calmodulin-dependent protein kinase II, which regulates atrial natriuretic factor gene expression.
Although isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been implicated in the regulation of gene expression in cultured cells, this issue has yet to be addressed in vivo. We report that the overexpression of calmodulin in ventricular myocytes of transgenic mice results in an increase in the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin transgene is regulated by a 500-bp fragment of the atrial natriuretic factor (ANF) gene promoter which, based on cell transfection studies, is itself known to be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the activity of the transgene and establishes a positive feed-forward loop, which also extends the temporal expression of the endogenous ANF promoter in ventricular myocytes. Both the increased activity of CaMKII and transcriptional activation of ANF are highly selective responses to the chronic overexpression of calmodulin. These results indicate that CaMKII can regulate gene expression in vivo and suggest that this enzyme may represent the Ca2+-dependent target responsible for reactivation of the ANF gene during ventricular hypertrophy.


Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton.
Netrin is a chemotrophic factor known to regulate a number of neurodevelopmental processes, including cell migration, axon guidance, and synaptogenesis. Although the role of Netrin in synaptogenesis is conserved throughout evolution, the mechanisms by which it instructs synapse assembly are not understood. Here we identify a mechanism by which the Netrin receptor UNC-40/DCC instructs synaptic vesicle clustering in vivo. UNC-40 localized to presynaptic regions in response to Netrin. We show that UNC-40 interacted with CED-5/DOCK180 and instructed CED-5 presynaptic localization. CED-5 in turn signaled through CED-10/Rac1 and MIG-10/Lamellipodin to organize the actin cytoskeleton in presynaptic regions. Localization of this signaling pathway to presynaptic regions was necessary for synaptic vesicle clustering during synapse assembly but not for the subcellular localization of active zone proteins. Thus, vesicle clustering and localization of active zone proteins are instructed by separate pathways downstream of Netrin. Our data indicate that signaling modules known to organize the actin cytoskeleton during guidance can be co-opted to instruct synaptic vesicle clustering.


HutZ is required for efficient heme utilization in Vibrio cholerae.
Vibrio cholerae, the causative agent of cholera, requires iron for growth. One mechanism by which it acquires iron is the uptake of heme, and several heme utilization genes have been identified in V. cholerae. These include three distinct outer membrane receptors, two TonB systems, and an apparent ABC transporter to transfer heme across the inner membrane. However, little is known about the fate of the heme after it enters the cell. In this report we show that a novel heme utilization protein, HutZ, is required for optimal heme utilization. hutZ (open reading frame [ORF] VCA0907) is encoded with two other genes, hutW (ORF VCA0909) and hutX (ORF VCA0908), in an operon divergently transcribed from the tonB1 operon. A hutZ mutant grew poorly when heme was provided as the sole source of iron, and the poor growth was likely due to the failure to use heme efficiently as a source of iron, rather than to heme toxicity. Heme oxygenase mutants of both Corynebacterium diphtheriae and C. ulcerans fail to use heme as an iron source. When the hutWXZ genes were expressed in the heme oxygenase mutants, growth on heme was restored, and hutZ was required for this effect. Biochemical characterization indicated that HutZ binds heme with high efficiency; however, no heme oxygenase activity was detected for this protein. HutZ may act as a heme storage protein, and it may also function as a shuttle protein that increases the efficiency of heme trafficking from the membrane to heme-containing proteins.


Changes in Children's Speech and Language Difficulties from Age Five to Nine: An Irish National, Longitudinal Study.
In many countries, information on the prevalence of persistent speech and language disorders in early childhood is sparse due to the lack of nationally representative samples and longitudinal studies. Secondary analysis of data collected on over 7500 Irish children at ages 5 and 9 years, found that the prevalence of speech and language difficulties reported by the primary caregivers of Irish children decreased from one in six at age 5 to one in 12 at age 9. However, one in 20 children were reported to have difficulties at both ages. Regression analysis compared children with difficulties at both age 5 and age 9 to those who had been reported to have them at age 5 but no longer had such difficulties at age 9. Children with speech and language difficulties at both age 5 and age 9 were more likely to have two or more developmental impairments as well as current or past hearing impairments. Teachers and parents also reported a greater number of social-emotional difficulties. Family characteristics did not differ significantly across the two groupings. At best, up to one third of the children at ages 5 and 9 with speech and language difficulties had two or more contacts with a speech and language therapists in the preceding 12 month period. Increased support to these children, their parents and teachers would seem to be warranted.


Update on primary hypobetalipoproteinemia.
"Primary hypobetalipoproteinemia" refers to an eclectic group of inherited lipoprotein disorders characterized by low concentrations of or absence of low-density lipoprotein cholesterol and apolipoprotein B in plasma. Abetalipoproteinemia and homozygous familial hypobetalipoproteinemia, although caused by mutations in different genes, are clinically indistinguishable. A framework for the clinical follow-up and management of these two disorders has been proposed recently, focusing on monitoring of growth in children and preventing complications by providing specialized dietary advice and fat-soluble vitamin therapeutic regimens. Other recent publications on familial combined hypolipidemia suggest that although a reduction of angiopoietin-like 3 activity may improve insulin sensitivity, complete deficiency also reduces serum cholesterol efflux capacity and increases the risk of early vascular atherosclerotic changes, despite low low-density lipoprotein cholesterol levels. Specialist laboratories offer exon-by-exon sequence analysis for the molecular diagnosis of primary hypobetalipoproteinemia. In the future, massively parallel sequencing of panels of genes involved in dyslipidemia may play a greater role in the diagnosis of these conditions.


Current issues and problems in the chemical vapor deposition of diamond.
Current issues and problems in the chemical vapor deposition (CVD) of diamond are those which relate to its characterization, its nucleation on foreign surfaces, the question of its formation in preference to the other phases of solid carbon (for example, graphite, chaoite, or lonsdaleite), why different morphologies and crystallographic orientations (textures) are seen in different experiments or with different parameters in the same experiment, and finally whether well-crystallized metastable phases can be obtained by CVD in other material systems or are only a peculiarity of carbon chemistry. Whether a given carbon coating is justly described as diamond has been such an issue, and coatings should clearly show evidence for diamond by x-ray diffraction and Raman spectroscopy before the claim of diamond is made. Experimental results have not been consistent in many cases, and much work remains to be done before an accurate assessment can be made of the technological impact of the development.


Obesity and major metabolic indices in newly diagnosed Saudi diabetic patients.
Metabolic indices were assessed in 217 Saudi diabetic patients and 57 control subjects in relation to Body Mass Index (BMI). Patients with BMI values greater than or equal to 27 in male and greater than or equal to 25 in female were considered obese. Obesity was found more frequent in females (82.7%) than in males (40.9%) (p less than 0.01). Basal glucose and HbA1C levels were lower in obese males than in females. C-peptide levels were higher (p less than 0.01) in the obese subjects than in the non-obese. Within the obese group c-peptide levels were higher in males than in females. Triglycerides and total lipids were also higher in the obese group. Our result suggests that a varying degree of obesity influences the rate of both beta cell secretion, insulin resistance and impaired lipid metabolism.


Characterization of normal feline renal vascular anatomy with dual-phase CT angiography.
Helical computed tomography angiography was used to evaluate the renal vascular anatomy of potential feline renal donors. One hundred and fourteen computed tomography angiograms were reviewed. The vessels were characterized as single without bifurcation, single with bifurcation, double, or triple. Multiplicity was most commonly seen for the right renal vein (45/114 vs. 3/114 multiple left renal veins, 0/114 multiple right renal arteries, and 8/114 multiple left renal arteries). The right kidney was 13.3 times more likely than the left to have multiple renal veins. Additional vascular variants included double caudal vena cava and an accessory renal artery. For the left kidney, surgery and computed tomography angiography findings were in agreement in 92% of 74 cats. For the right kidney, surgery and computed tomography angiography findings were in agreement in 6/6 cats. Our findings of renal vascular anatomy variations in cats were similar to previous reports in humans. Identifying and recognizing the pattern of distribution of these vessels is important when performing renal transplantation.


The Course and Interaction of Ventriculomegaly and Cerebellar Tonsillar Herniation in Crouzon Syndrome over Time.
Children with Crouzon syndrome have a higher incidence of cerebellar tonsillar herniation (TH) and ventriculomegaly than the general population, or children with other craniosynostosis syndromes. This retrospective cohort study aimed to determine how ventriculomegaly and TH develop and progress over time, and determine associations between ventriculomegaly and TH in Crouzon patients, treated according to our center's protocol. Fronto-occipital horn ratio (FOHR) and TH were determined over time using brain-imaging. These data were used to fit a mixed-model to determine associations between them, and with clinical variables, head-circumference, and lambdoid suture synostosis. Sixty-three Crouzon patients were included in this study. Preoperatively, 28% had ventriculomegaly, and 11% had TH ≥ +5 mm. Postoperatively ventriculomegaly increased to 49%. Over time and with treatment, FOHR declined and stabilized around 5 years of age. TH ≥ +5 mm increased to 46% during follow-up. FOHR and TH were associated: expected FOHR with a TH of either 0 mm versus +8.6 mm at 0 years: 0.44 versus 0.49, and at 5 years: 0.34 versus 0.38; 10% increase of FOHR was associated with 1.6 mm increase in TH. Increased head-circumference was associated with increased FOHR. Lambdoid suture synostosis was associated with +6.9 mm TH increase. In Crouzon patients, FOHR was large at onset and decreased and stabilized with treatment and time. FOHR was associated with head-circumference and TH. TH was strongly associated with lambdoid suture synostosis and FOHR. Increased head-circumference was associated with an increased FOHR, and closed lambdoid sutures before 1 year of age were associated with a +6.92 mm increase in tonsil position.


Assessment of physical activity with a single global question in a large, multiethnic sample of midlife women.
This study compared responses from 13,621 African-American, Chinese, Hispanic, Japanese, and White women to a single, global physical activity question. Respondents aged 40-55 years were randomly selected from seven geographic locations in the United States for the 1996-1997 cross-sectional survey of the Study of Women's Health Across the Nation, a longitudinal, observational study of the menopause transition. Respondents rated their activity level as much less, less, the same as, more, or much more than other women their age. Physical activity rating varied minimally by race/ethnicity. The proportions of women who rated themselves much less active and much more active ranged from 3.1% for Whites to 4.8% for Japanese and from 13.6% for Japanese to 16.4% for African Americans, respectively. Multiple logistic regression models, stratified by race/ethnicity, showed independent associations between a low level of activity and higher body mass index, poor health, functional impairment, perceived stress, difficulty sleeping, and not being employed. A high level of activity was associated with excellent health, single marital status, higher education, lower body mass index, and older age. These findings suggest that a comparative rating of physical activity may rank women by activity level within a specific racial/ethnic group but may not capture differences across racial/ethnic groups.


Knowledge, attitudes and practices towards avian influenza among live poultry market workers in Chongqing, China.
Live poultry market (LPM) workers are at high risk of infection with avian influenza virus due to frequent occupational exposure to poultry. This study aims to assess the knowledge, attitude and preventive practice regarding avian influenza among LPM workers in Chongqing, the largest municipality directly under the central government of China. 216 LPM workers were recruited by two-stage cluster sampling and interviewed face-to-face using a structured questionnaire. Hierarchical logistic regression analysis was performed to explore factors associated with preventive practices against avian influenza and views on government control measures. Nearly half of respondents failed to recognize contact with sick birds or excrement as a risk of infection. Less than half the respondents perceived themselves to have a personal susceptibility to be infected or would like to enhance personal protection. Respondents did not pay sufficient attention to wearing preventive clothing such as gloves (43.1%), aprons/garments (33.3%) and face masks (26.9%) when handling live poultry. Few respondents were supportive to market control measures such as a ban on birds' overnight storage (26.8%) or a regular rest day (32.4%). Being older, being more highly educated, having worked longer with poultry, having better knowledge, having more access to information, and perceiving more personal susceptibility to the disease were positively associated with preventive practices. Having higher personal income, longer engagement with poultry work, better knowledge, more awareness of personal protection were positively associated with agreement with government control measures. LPM workers in Chongqing showed low level of knowledge, weak perception of susceptibility to avian influenza and inadequate preventive behaviors. Health education campaigns need to better target the knowledge on transmission routes and potential outbreak threat of avian influenza. More attention should be paid to LPM workers who are younger, less educated, with shorter occupational years and lower personal income.


Integrating quality management into clinical systems: tools for achieving clinical integration.
This article describes the use of quality systems as a tool for managers of health-care clinical services to establish a common framework across the different disciplines in the continuum of care. Quality systems used internationally in the manufacturing and service sectors are applicable to multidisciplinary clinical systems management because the essential elements of quality are universal. These elements have been redefined into health-care terminology and can be used by clinical systems managers as a basis for implementing a quality system. The structure for documents in a quality system also has been adapted to health care and allows for a common set of quality policies and processes to unify the different clinical services. By using a consistent quality management approach and documentation, managers can transcend technical operational differences and ensure effective clinical integration.


A controlled study of L-DOPA in Parkinson's disease.
A small group of patients with Parkinson's disease were treated with oral l-dopa. In ten cases the drug was given according to a randomized, double-blind-crossover protocol, and in 13 cases both the physician and the patient knew what treatment was being given. With subjective bias at a minimum the salutary effects of the amino acid were confirmed in 90 percent of the patients. The general level of improvement with l-dopa was better than with standard agents, and a combination of drugs was sometimes very helpful. Toxic psychosis was a problem in three cases, but other adverse reactions were minimal. Further extensive trial and study is indicated.


Exercise versus no exercise for the occurrence, severity and duration of acute respiratory infections.
Acute respiratory infections (ARIs) last for less than 30 days and are the most common acute diseases affecting people worldwide. Exercise has been shown to improve health generally and may be effective in reducing the occurrence, severity and duration of acute respiratory infections. To evaluate the effectiveness of exercise for altering the occurrence, severity or duration of acute respiratory infections. We searched CENTRAL (2014, Issue 6), MEDLINE (1948 to July week 1, 2014), EMBASE (2010 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014), SPORTDiscus (1985 to July 2014), PEDro (searched on 11 July 2014), OTseeker (searched on 11 July 2014), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (searched on 11 July 2014). Randomised controlled trials (RCTs) and quasi-RCTs of exercise for ARIs in the general population. Two review authors independently extracted data from the included trials using a standard form. We contacted trial authors to request missing data. One review author entered data and a second review author checked this. There were sufficient differences in the populations trialled and in the nature of the interventions to use the random-effects model (which makes fewer assumptions than the fixed-effect model) in the analysis. We included 11 trials involving 904 adults, published between 1990 and 2014. Eight studies were conducted in the USA, and one each in Canada, Spain and Turkey. Sample sizes ranged from 20 to 154 participants aged between 18 and 85 years old. The proportion of female participants varied between 52% and 100%. The duration of follow-up in the studies varied from seven days to 12 months. The exercise type most prescribed for the intervention was aerobic (walking in 70% of the studies, or bicycle riding or treadmill) at least five times a week. Duration was 30 to 45 minutes at moderate intensity. Participants were supervised in 90% of the studies.For four of the primary outcomes the results did not differ significantly and all were low-quality evidence (number of ARI episodes per person per year, rate ratio 0.91 (95% confidence interval (CI) 0.59 to 1.42); proportion of participants who experienced at least one ARI over the study period, risk ratio 0.76 (95% CI 0.57 to 1.01); severity of ARI symptoms, mean difference (MD) -110 (95% CI -324 to 104); and number of symptom days in the follow-up period, MD -2.1 days (95% CI -4.4 to 0.3)). However, one primary outcome, the number of symptom days per episode of illness, was reduced in those participants who exercised (MD -1.1 day, 95% CI -1.7 to -0.5, moderate-quality evidence).We found no significant differences for the secondary outcomes (laboratory parameters (blood lymphocytes, salivary secretory immunoglobulin and neutrophils); quality of life outcomes; cost-effectiveness and exercise-related injuries).There was good adherence to the intervention with no difference between the exercise and non-exercise groups.We rated the quality of evidence for the primary outcomes as low for most outcomes using the GRADE criteria: allocation concealment was not reported and there was a lack of blinding; in addition, there was imprecision (the CI is very wide because of a small number of participants) and inconsistency, which may be due to differences in study design. We cannot determine whether exercise is effective at altering the occurrence, severity or duration of acute respiratory infections. One analysis of four trials suggests that the number of days of illness per episode of infection might be reduced by exercise. The small size of the studies, risk of bias and heterogeneous populations trialled all contribute to the uncertainty. Larger studies, with less risk of bias from patient selection, blinding of outcomes assessors, reporting of all outcomes measured and with registration of study protocols, are required to settle the question.


Influence of inflammation on voriconazole metabolism.
Voriconazole pharmacokinetics shows a large inter- and intrapatient variability. Inflammation is associated with changes in the expression of CYP isoenzymes. Here, we evaluated the influence of inflammation, marked by C-reactive protein (CRP) levels in blood, on the metabolism of voriconazole. Observational data showed an association between CRP level and the ratio of voriconazole N-oxide to voriconazole.