Daratumumab-based therapies in transplant-ineligible patients with untreated multiple myeloma and hepatic dysfunction: A systematic review of subgroup analyses.
There is subgroup analysis suggesting a lack of benefit of daratumumab use in multiple myeloma (MM) and hepatic disease (HD). The objectives of this study were to conduct a systematic review and interpretation of daratumumab-based regimen efficacy in transplant-ineligible patients with untreated MM and HD. A systematic search in Pubmed® database about randomized clinical trials (RCTs) with subgroup analysis regarding hepatic function for overall survival (OS) or progression-free survival (PFS) were developed. Two methodologies were applied. One of them considered statistical interaction, prespecification, biological support and consistency of subgroup results. Second methodology was two-part validated tool: preliminary questions to reject subset analysis without minimal relevance, and a checklist relating a recommendation for applicability in clinical practice. It was included three records. About first methodology, statistical interaction among subgroups was found for PFS in one RCT. Subsets were prespecified in all RCTs. Biological support of efficacy differences could be reasonable. Inconsistent results were found. Second methology directly rejected applicability of subset analysis in two records. Checklist recommended "null" application of results in the remaining RCT. No consistent heterogeneity for daratumumab-based regimen efficacy was observed among subgroups regarding hepatic function in transplant-ineligible patients with untreated MM. Patients with normal hepatic function and HD could benefit from these treatments.


Role of Nanotechnology and Their Perspectives in the Treatment of Kidney Diseases.
Nanoparticles (NPs) are differing in particle size, charge, shape, and compatibility of targeting ligands, which are linked to improved pharmacologic characteristics, targetability, and bioavailability. Researchers are now tasked with developing a solution for enhanced renal treatment that is free of side effects and delivers the medicine to the active spot. A growing number of nano-based medication delivery devices are being used to treat renal disorders. Kidney disease management and treatment are currently causing a substantial global burden. Renal problems are multistep processes involving the accumulation of a wide range of molecular and genetic alterations that have been related to a variety of kidney diseases. Renal filtration is a key channel for drug elimination in the kidney, as well as a burgeoning topic of nanomedicine. Although the use of nanotechnology in the treatment of renal illnesses is still in its early phases, it offers a lot of potentials. In this review, we summarized the properties of the kidney and characteristics of drug delivery systems, which affect a drug's ability should focus on the kidney and highlight the possibilities, problems, and opportunities.


Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection.
This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection. From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy. The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1-4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1-5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1-4 months, and patients who did not receive chemotherapy until >5 weeks after surgery. The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.


CD4 and CD8 cell responses to herpes simplex virus in Behçet's disease.
The finding of part of the Herpes simplex virus type 1 (HSV1) genome in peripheral blood leucocytes of some patients with Behcet's disease (BD) led to investigations of T cell responses to HSV1 in this disease. A significantly impaired uptake of 3H-thymidine by CD4 cells was found in BD, as compared with healthy HSV1 sero-positive subjects. The impaired cellular response appeared to be specific to HSV1, as neither cytomegalovirus nor varicella-zoster virus showed depressed CD4 cell responses in BD. A similar impairment of CD4 cell responses to HSV1 was found in patients with recurrent herpetic infections, known to be caused by latent HSV1 infections. However, in rheumatoid arthritis which was selected as an unrelated autoimmune disease. 3H-thymidine uptake by CD4 cells stimulated with HSV1 was enhanced. CD8 cells showed generally rather a low uptake of 3H-thymidine, nevertheless, the values in BD and recurrent herpetic infection were again lower than those in sero-positive controls or rheumatoid arthritis. The results are consistent with the hypothesis that HSV1 might be involved in the immunopathogenesis of BD.


Biological effects of heavy metals: an overview.
Heavy metals constitute a very heterogeneous group of elements widely varied in their chemical properties and biological functions. Heavy metals are kept under environmental pollutant category due to their toxic effects on plants, animals and human being. Heavy metal contamination of soil results from anthropogenic as well as natural activities. Anthropogenic activities such as mining, smelting operation and agriculture have locally increased the levels of heavy metals such as Cd, Co, Cr, Pb, As and Ni in soil up to dangerous levels. Heavy metals are persistent in nature, therefore get accumulated in soils and plants. Heavy metals interfere with physiological activities of plants such as photosynthesis, gaseous exchange and nutrient absorption, and cause reductions in plant growth, dry matter accumulation and yield. Heavy metals also interfere with the levels of antioxidants in plants, and reduce the nutritive value of the produce. Dietary intake of many heavy metals through consumption of plants has long term detrimental effects on human health.


DJ-1 Modulates Nuclear Erythroid 2-Related Factor-2-Mediated Protection in Human Primary Alveolar Type II Cells in Smokers.
Cigarette smoke (CS) is a main source of oxidative stress and a key risk factor for emphysema, which consists of alveolar wall destruction. Alveolar type (AT) II cells are in the gas exchange regions of the lung. We isolated primary ATII cells from deidentified organ donors whose lungs were not suitable for transplantation. We analyzed the cell injury obtained from nonsmokers, moderate smokers, and heavy smokers. DJ-1 protects cells from oxidative stress and induces nuclear erythroid 2-related factor-2 (Nrf2) expression, which activates the antioxidant defense system. In ATII cells isolated from moderate smokers, we found DJ-1 expression by RT-PCR, and Nrf2 and heme oxygenase (HO)-1 translocation by Western blotting and immunocytofluorescence. In ATII cells isolated from heavy smokers, we detected Nrf2 and HO-1 cytoplasmic localization. Moreover, we found high oxidative stress, as detected by 4-hydroxynonenal (4-HNE) (immunoblotting), inflammation by IL-8 and IL-6 levels by ELISA, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in ATII cells obtained from heavy smokers. Furthermore, we detected early DJ-1 and late Nrf2 expression after ATII cell treatment with CS extract. We also overexpressed DJ-1 by adenovirus construct and found that this restored Nrf2 and HO-1 expression and induced nuclear translocation in heavy smokers. Moreover, DJ-1 overexpression also decreased ATII cell apoptosis caused by CS extract in vitro. Our results indicate that DJ-1 activates the Nrf2-mediated antioxidant defense system. Furthermore, DJ-1 overexpression can restore the impaired Nrf2 pathway, leading to ATII cell protection in heavy smokers. This suggests a potential therapeutic strategy for targeting DJ-1 in CS-related lung diseases.


Evaluation of image reconstruction for mouse brain imaging with synthetic collimation from highly multiplexed SiliSPECT projections.
We have performed a theoretical study to explore the potential and limitations of synthetic collimation for SPECT imaging with stacked-detector acquisition (dual magnification). This study will be used to optimize SiliSPECT, a small-animal SPECT for imaging small volumes such as a mouse brain at high sensitivity and resolution. The synthetic collimation enables image reconstruction with a limited number of camera views and in the presence of significant multiplexing. We also developed a new formulation to quantify the multiplexed object sensitivity and investigated how this changes for different acquisition parameters such as number of pinholes and combinations of front and back detector distances for imaging objects as small as the mouse brain. In our theoretical studies, we were not only able to demonstrate better reconstruction results by incorporating two detector magnifications in comparison to either one alone, but also observed an improved image reconstruction by optimizing the detector-collimator distances to change the multiplexing ratio between the front and back detectors.


Evaluation of the craniocervical junction in Down syndrome: correlation of measurements obtained with radiography and MR imaging.
Measurement of the atlas-dens interval is the radiographic standard for identification of patients with Down syndrome at high risk for neurologic injury from spinal cord compression. In 17 pediatric patients with Down syndrome, measurements of the atlas-dens interval, distance between the clivus and posterior odontoid process, and width of the neural canal obtained with plain radiographs were compared to predict the width of the subarachnoid space on magnetic resonance (MR) images. In all patients, cervical radiography and craniocervical MR imaging were prospectively performed during lateral flexion and extension. The width of the subarachnoid space was measured with MR imaging. When the 95% confidence interval for correlation coefficients of regression was used, subarachnoid space width on MR images correlated with neural canal width on radiographs better than with either atlas-dens interval or clivus-posterior odontoid process distance (P = .05). Measurement of neural canal width is a better predictor of potential spinal cord compression than the atlas-dens interval or clivus-posterior odontoid process distance and should be emphasized in screening examinations performed with plain radiography.


Application of models of defibrillation to human defibrillation data: implications for optimizing implantable defibrillator capacitance.
Theoretical models predict that optimal capacitance for implantable cardioverter-defibrillators (ICDs) is proportional to the time-dependent parameter of the strength-duration relationship. The hyperbolic model gives this relationship for average current in terms of the chronaxie (t(c)). The exponential model gives the relationship for leading-edge current in terms of the membrane time constant (tau(m)). We hypothesized that these models predict results of clinical studies of ICD capacitance if human time constants are used. We studied 12 patients with epicardial ICDs and 15 patients with transvenous ICDs. Defibrillation threshold (DFT) was determined for 120-microF monophasic capacitive-discharge pulses at pulse widths of 1.5, 3.0, 7.5, and 15 ms. To compare the predictions of the average-current versus leading-edge-current methods, we derived a new exponential average-current model. We then calculated individual patient time parameters for each model. Model predictions were validated by retrospective comparison with clinical crossover studies of small-capacitor and standard-capacitor waveforms. All three models provided a good fit to the data (r2=.88 to .97, P<.001). Time constants were lower for transvenous pathways (53+/-7 omega) than epicardial pathways (36+/-6 omega) (t(c), P<.001; average-current tau(m), P=.002; leading-edge-current tau(m), P<.06). For epicardial pathways, optimal capacitance was greater for either average-current model than for the leading-edge-current model (P<.001). For transvenous pathways, optimal capacitance differed for all three models (P<.001). All models provided a good correlation with the effect of capacitance on DFT in previous clinical studies: r2=.75 to .84, P<.003. For 90-microF, 120-microF, and 150-microF capacitors, predicted stored-energy DFTs were 3% to 8%, 8% to 16%, and 14% to 26% above that for the optimal capacitance. Model predictions based on measured human cardiac-muscle time parameter have a good correlation with clinical studies of ICD capacitance. Most of the predicted reduction in DFT can be achieved with approximately 90-microF capacitors.


Feeding entrainment of food-anticipatory activity and per1 expression in the brain and liver of zebrafish under different lighting and feeding conditions.
Food provided on a periodic basis can act as a potent synchronizer, being a stronger zeitgeber than light for peripheral oscillators in mammals. In fish, however, little is known about the influence of feeding time on the circadian pacemaker and the relationship between central and peripheral oscillators. The aim of this research was to investigate the influence of mealtime on the activity rhythms, and on central (brain) and peripheral (liver) oscillators in zebrafish. The authors tested different feeding times under a light-dark (LD) cycle and the endogenous origin of food-anticipatory activity (FAA) by feeding zebrafish at a fixed time under constant bright-light conditions (LL). The authors then measured locomotor activity and the expression of the clock gene per1 in animals under a LD cycle and fed at random times during the light phase, with restricted feeding at the mid-light phase (ML) or with restricted feeding during the mid-dark phase (MD). Finally, the authors measured locomotor activity and per1 expression in fish maintained under LL under either random feeding or scheduled feeding. Zebrafish displayed FAA in all the groups fed at a fixed time but not when feeding was randomly scheduled. Under LL, fish entrainment persisted, and when released under fasting conditions FAA free-ran with a circa-24-h period. The expression of per1 in the brain of fish under LD showed a daily rhythm with the acrophase (peak time) at the end of the dark phase regardless of feeding schedule. This brain rhythm disappeared in LL fish under both random feeding and scheduled feeding. Feeding at MD advanced the phase of per1 in the liver by 7 h compared with the ML-fed group phase (23:54 versus 07:23 h, respectively). In addition, under LL scheduled feeding entrained the rhythms of per1 expression in the liver. This study reveals for the first time that scheduled feeding entrains peripheral oscillators in a fish species, zebrafish, which is a powerful model widely used for molecular genetics and for the study of basic clock mechanisms of the vertebrate circadian system.


Comparison of the medical priority dispatch system to an out-of-hospital patient acuity score.
Although the Medical Priority Dispatch System (MPDS) is widely used by emergency medical services (EMS) dispatchers to determine dispatch priority, there is little evidence that it reflects patient acuity. The Canadian Triage and Acuity Scale (CTAS) is a standard patient acuity scale widely used by Canadian emergency departments and EMS systems to prioritize patient care requirements. To determine the relationship between MPDS dispatch priority and out-of-hospital CTAS. All emergency calls on a large urban EMS communications database for a one-year period were obtained. Duplicate calls, nonemergency transfers, and canceled calls were excluded. Sensitivity and specificity to detect high-acuity illness, as well as positive predictive value (PPV) and negative predictive value (NPV), were calculated for all protocols. Of 197,882 calls, 102,582 met inclusion criteria. The overall sensitivity of MPDS was 68.2% (95% confidence interval [CI] = 67.8% to 68.5%), with a specificity of 66.2% (95% CI = 65.7% to 66.7%). The most sensitive protocol for detecting high acuity of illness was the breathing-problem protocol, with a sensitivity of 100.0% (95% CI = 99.9% to 100.0%), whereas the most specific protocol was the one for psychiatric problems, with a specificity of 98.1% (95% CI = 97.5% to 98.7%). The cardiac-arrest protocol had the highest PPV (92.6%, 95% CI = 90.3% to 94.3%), whereas the convulsions protocol had the highest NPV (85.9%, 95% CI = 84.5% to 87.2%). The best-performing protocol overall was the cardiac-arrest protocol, and the protocol with the overall poorest performance was the one for unknown problems. Sixteen of the 32 protocols performed no better than chance alone at identifying high-acuity patients. The Medical Priority Dispatch System exhibits at least moderate sensitivity and specificity for detecting high acuity of illness or injury. This performance analysis may be used to identify target protocols for future improvements.


The concave face of decorin mediates reversible dimerization and collagen binding.
Decorin, the prototypical small leucine-rich proteoglycan, binds to collagen and thereby regulates collagen assembly into fibrils. The crystal structure of the decorin core protein revealed a tight dimer formed by the association of two monomers via their concave faces (Scott, P. G., McEwan, P. A., Dodd, C. M., Bergmann, E. M., Bishop, P. N., and Bella, J. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 15633-15638). Whether decorin binds collagen as a dimer has been controversial. Using analytical ultracentrifugation, we determined a dissociation constant of 1.37 ± 0.30 μm for the mouse decorin dimer. Dimerization could be abolished by engineering glycosylation sites into the dimer interface; other interface mutants remained dimeric. The monomeric mutants were as stable as wild-type decorin in thermal unfolding experiments. Mutations on the concave face of decorin abolished collagen binding regardless of whether the mutant proteins retained the ability to dimerize or not. We conclude that the concave face of decorin mediates collagen binding and that the dimer therefore must dissociate to bind collagen.


Impact of early and delayed stroke on in-hospital and long-term mortality after isolated coronary artery bypass grafting.
Stroke after coronary artery bypass grafting (CABG) is an infrequent, yet devastating complication with increased morbidity and mortality. We sought to determine risk factors for early (intraoperatively to 24 hours) and delayed (>24 hours to discharge) stroke and to identify their impact on long-term mortality after CABG. We studied 4,140 consecutive patients who underwent isolated CABG from 1992 to 2003. Long-term survival data (mean follow-up 7.4 years) were obtained from the National Death Index. Independent predictors for stroke and in-hospital mortality were determined by multivariate logistic regression analysis including all available preoperative, intraoperative, and postoperative risk factors. Independent predictors for long-term mortality were determined by multivariate Cox regression analysis. One hundred two patients (2.5%) developed early stroke and 36 patients (0.9%) delayed stroke. Independent predictors for early stroke were age, recent myocardial infarction, smoking, femoral vascular disease, body mass index, reoperation for bleeding, postoperative sepsis and/or endocarditis, and respiratory failure, whereas those for delayed stroke were female gender, white race, preoperative renal failure, respiratory failure, and postoperative renal failure. Early stroke was an independent predictor for in-hospital (odds ratio 3.49, 95% confidence interval [CI] 1.56 to 7.80, p = 0.002) and long-term (hazard ratio 1.70, 95% CI 1.30 to 2.21, p <0.001) mortalities. Delayed stroke was not an independent predictor for in-hospital (odds ratio 0.90, 95% CI 0.23 to 3.51, p = 0.878) or long-term (hazard ratio 0.66, 95% CI 0.38 to 1.17, p = 0.156) mortality. In conclusion, risk factors for early in-hospital stroke differ from those of delayed in-hospital stroke after CABG. Early stroke is an independent predictor for in-hospital and long-term mortalities, suggesting the need for a more frequent follow-up and appropriate pharmacologic therapy after discharge.


Relationship of smoking and fibrosis in patients with chronic hepatitis C.
Preliminary studies have suggested that in patients with chronic hepatitis C (CHC), cigarette smoking increases the risk for developing liver fibrosis. Hypoxia caused by smoking may induce expression of the cytokines' vascular endothelial growth factor (VEGF) and VEGF-D and their corresponding soluble tyrosine kinase receptors fms-like tyrosine kinase receptor (s-Flt) and kinase insert domain receptor (s-KDR). These cytokine levels are increased in animals with cirrhosis and in human beings with CHC. We studied whether the concentrations of VEGF, VEGF-D, s-Flt, and s-KDR were increased in CHC smokers with and without hepatic fibrosis. A total of 170 CHC patients were identified retrospectively from a single center's database. In 59 patients, serum levels of VEGF, VEGF-D, s-Flt, and s-KDR were measured using an enzyme-linked immunosorbent assay. All 170 patients were hepatitis C virus RNA positive, 117 (69%) were men, 43 (25%) were smokers, and their mean (+/-SD) age was 47 (+/-6) years. Overall, 21% of smokers had Metavir fibrosis scores of 3 and 4 compared with 14% of nonsmokers (P < .01). In an age-weighted multivariate model using step-wise logistic regression, smoking, infection with hepatitis C virus genotype 1, male sex, and increased VEGF-D concentration all were significant independent predictors of more severe liver fibrosis (P < .05 for all observations). These data suggest that CHC patients who smoke may have more hepatic fibrosis. The data also suggest that increased VEGF and VEGF-D concentrations are associated with smoking and may be involved in the molecular mechanisms of fibrogenesis.


Exposure of eyes to laser radiation during dental surgery.
Fifty patients admitted to the clinic because of dental surgery were subjected to biostimulative laser therapy. Ophthalmological examinations were performed in each patient prior and after laserotherapy. The results were estimated according to the occurrence of lacrimation, redness of the conjunctiva, photophobia and the changed retinal reflex to the light. No pathological changes were revealed in the treated patients who had used protective glasses during the laserotherapy.


Insulin and oral antidiabetic agents for treatment of polycystic ovary syndrome.
Insulin plays a major role in polycystic ovary syndrome (PCOS). Insulin resistance and resultant hyperinsulinemia stimulate both the ovary and adrenal to produce androgens. Oral antidiabetic agents have been used to alleviate the symptoms and to induce ovulation in women with PCOS. This review focuses on the relation between insulin and PCOS and discusses the use of oral antidiabetic agents.


Practice patterns of obstetrician-gynecologists regarding preconception and prenatal screening for cystic fibrosis.
To assess practices of obstetrician-gynecologists regarding carrier screening for cystic fibrosis (CF). A questionnaire investigating practice patterns and opinions pertaining to CF screening was mailed to 1165 members of the American College of Obstetricians and Gynecologists (ACOG), of whom 565 participate in the Collaborative Ambulatory Research Network (CARN) and 600 were randomly selected. Of the questionnaires, 64% were returned. Statistical analyses were limited to the 632 respondents whose primary medical specialty was gynecology (Gyn Only) or obstetrics and gynecology (ObGyn). CARN membership was not a significant factor on any nondemographic measure. Almost one-half of physicians do not ask nonpregnant patients their family history of CF or provide them with information about CF screening. The majority of ObGyns (88.7%) ask obstetric patients their family history of CF, and offer CF carrier screening. Almost two-thirds (65.8%) offer screening to all prenatal patients. Among those ObGyns who selectively offer CF screening to pregnant patients, only 27.4% utilized all of the selection criteria in the guidelines. Liability for not offering screening, familiarity with CF, and the ability to interpret a positive screening test were important physician concerns. The results indicate a need for minimizing the complexity of clinical guidelines for population-based genetic screening, prospective assessment of implementation and focused continuing education for providers.


Dendritic cells in cytomegalovirus infection: viral evasion and host countermeasures.
Human cytomegalovirus (HCMV) is a beta-herpesvirus that infects the majority of the population during early childhood and thereafter establishes life-long latency. Primary infection as well as spontaneous reactivation usually remains asymptomatic in healthy hosts but can, in the context of systemic immunosuppression, result in substantial morbidity and mortality. HCMV counteracts the host immune response by interfering with the recognition of infected cells. A growing body of literature has also suggested that the virus evades the immune system by paralyzing the initiators of antiviral immune responses--the dendritic cells (DCs). In the current review, we discuss the effects of CMV (HCMV and murine CMV) on various DC subsets and the ensuing innate and adaptive immune responses. The impact of HCMV on DCs has mainly been investigated using monocyte-derived DCs, which are rendered functionally impaired by infection. In mouse models, DCs are targets of viral evasion as well, but the complex cross-talk between DCs and natural killer cells has, however, demonstrated an instrumental role for DCs in the control and clearance of viral infection. Fewer studies address the role of peripheral blood DC subsets, plasmacytoid DCs and CD11c+ myeloid DCs in the response against HCMV. These DCs, rather than being paralyzed by HCMV, are largely resistant to infection, mount a vigorous first-line defense and induce T-cell responses to the virus. This possibly provides a partial explanation for an intriguing conundrum: the highly efficient control of viral infection and reactivation in immunocompetent hosts in spite of multi-layered viral evasion mechanisms.


Incidence and Risk Factors for Chronic Anterior Knee Pain.
Chronic anterior knee pain is a common clinical entity, more so in the active individual. The incidence and risk factors, however remain unexplored. We investigated the correlation of demographic and occupational risk factors as well as the incidence of chronic anterior knee pain in an active military population. We performed a retrospective review of all U. S. Military active duty service members with the diagnosis of chondromalacia patellae, representative of the clinical syndrome of chronic anterior knee pain, between 2006 and 2012 using the Defense Medical Epidemiology Database. The demographic and occupation risk factors were categorized and the subgroup and overall incidence rates were determined via multivariable analysis. A total of 42,040 cases of chondromalacia patellae were identified in an at-risk population of 9,723,449, corresponding to an incidence rate of 4.32 cases per 1,000 person-years. Increasing chronological age, female sex, Black race, junior enlisted rank, and primary ground forces (Marines and Army) significantly correlated with an increased risk for chronic anterior knee pain. This study is the first report of incidence and risk factors for chondromalacia patellae in a large athletic population. We determined that sex, age, race, branch of service, and rank all correlated with the incidence of chondromalacia patellae in an active population.


Genetic heterogeneity in self-reported depressive symptoms identified through genetic analyses of the PHQ-9.
Depression is a clinically heterogeneous disorder. Previous large-scale genetic studies of depression have explored genetic risk factors of depression case-control status or aggregated sums of depressive symptoms, ignoring possible clinical or genetic heterogeneity. We analyse data from 148 752 subjects of white British ancestry in the UK Biobank who completed nine items of a self-rated measure of current depressive symptoms: the Patient Health Questionnaire (PHQ-9). Genome-Wide Association analyses were conducted for nine symptoms and two composite measures. LD Score Regression was used to calculate SNP-based heritability (h2SNP) and genetic correlations (rg) across symptoms and to investigate genetic correlations with 25 external phenotypes. Genomic structural equation modelling was used to test the genetic factor structure across the nine symptoms. We identified nine genome-wide significant genomic loci (8 novel), with no overlap in loci across symptoms. h2SNP ranged from 6% (concentration problems) to 9% (appetite changes). Genetic correlations ranged from 0.54 to 0.96 (all p < 1.39 × 10-3) with 30 of 36 correlations being significantly smaller than one. A two-factor model provided the best fit to the genetic covariance matrix, with factors representing 'psychological' and 'somatic' symptoms. The genetic correlations with external phenotypes showed large variation across the nine symptoms. Patterns of SNP associations and genetic correlations differ across the nine symptoms, suggesting that current depressive symptoms are genetically heterogeneous. Our study highlights the value of symptom-level analyses in understanding the genetic architecture of a psychiatric trait. Future studies should investigate whether genetic heterogeneity is recapitulated in clinical symptoms of major depression.


Change, Connectivity, and Challenge: Exploring the Role of Health Technology in Shaping Health Care for Aging Populations in Asia Pacific.
Aflthough the rapid increase in population aging observed across the globe poses significant challenges to the sustainability of health systems it has been paralleled by an exponential growth in health technologies. This article reviews the literature surrounding health technologies and explores how the future of aging and health care could be shaped by health technologies, with a particular focus on the Asia Pacific region. It shows that the field is wide in scope. The current expansion of information and communication technologies have brought a growing capacity to support health care, while future technology applications, such as robotics and 3D printing, offer a range of potential benefits to elderly populations. However, the uptake and level of development of health technologies varies widely throughout the region. Governments have begun developing frameworks to guide the implementation and monitoring of health technologies. However, a dearth of robust, evaluative studies, combined with the rapidly evolving nature of health technologies, present policy makers with a range of policy and implementation challenges, including issues surrounding infrastructure, funding, and the acceptability of technologies among older users. As health technologies play an increasingly pivotal part in health systems, there is a need to create robust mechanisms for ongoing assessment of health technology development.


Integration of gene maps: updating chromosome 1.
The first integrated map of chromosome 1 was published in 1992. We present an updated summary map of 371 loci constructed from a location database that includes physical and genetic data. The summary map subsumes a composite physical location, sex-specific genetic location, cytogenetic assignment, mouse homology, rank and references to physical maps. The genetic length is 208 cM for the male map, in close agreement with the chiasma map, and 371 cM for the female map. There is evidence for a high level of interference on chromosome 1. The location database comprising both data and analytical software is discussed in relation to alternative approaches and possible enhancements.


Fungal root endophytes of the carnivorous plant Drosera rotundifolia.
As carnivorous plants acquire substantial amounts of nutrients from the digestion of their prey, mycorrhizal associations are considered to be redundant; however, fungal root endophytes have rarely been examined. As endophytic fungi can have profound impacts on plant communities, we aim to determine the extent of fungal root colonisation of the carnivorous plant Drosera rotundifolia at two points in the growing season (spring and summer). We have used a culture-dependent method to isolate fungal endophytes and diagnostic polymerase chain reaction methods to determine arbuscular mycorrhizal fungi colonisation. All of the roots sampled contained culturable fungal root endophytes; additionally, we have provided molecular evidence that they also host arbuscular mycorrhizal fungi. Colonisation showed seasonal differences: Roots in the spring were colonised by Articulospora tetracladia, two isolates of uncultured ectomycorrhizal fungi, an unidentified species of fungal endophyte and Trichoderma viride, which was present in every plant sampled. In contrast, roots in the summer were colonised by Alatospora acuminata, an uncultured ectomycorrhizal fungus, Penicillium pinophilum and an uncultured fungal clone. Although the functional roles of fungal endophytes of D. rotundifolia are unknown, colonisation may (a) confer abiotic stress tolerance, (b) facilitate the acquisition of scarce nutrients particularly at the beginning of the growing season or (c) play a role in nutrient signalling between root and shoot.


Aromatase inhibitor associated musculoskeletal symptoms are associated with reduced physical activity among breast cancer survivors.
Physical activity (PA) has numerous health benefits for breast cancer survivors. Recent data suggest that some breast cancer survivors treated with aromatase inhibitors may experience aromatase inhibitor associated musculoskeletal symptoms. It is unknown whether aromatase inhibitor associated musculoskeletal symptoms are associated with reduced PA and what other risk factors are associated with such PA reductions. We conducted a cross-sectional study at a large university-based breast cancer clinic among breast cancer survivors prescribed an aromatase inhibitor. At routine follow-up, we surveyed participants about aromatase inhibitor associated musculoskeletal symptoms, as well as pre-aromatase inhibitor, and current, PA levels. Among 300 participants, 90 (30%) reported a reduction of PA since the initiation of aromatase inhibitor therapy. Those with aromatase inhibitor associated musculoskeletal symptoms were more likely to report decreased PA (62% versus 38%, p = 0.001) compared with those without aromatase inhibitor associated musculoskeletal symptoms. In multivariate analyses, aromatase inhibitor associated musculoskeletal symptoms (odds ratio [OR] = 2.29 [95% confidence interval [CI]: 1.36-3.86]), and body mass index (OR = 1.06 [95% CI: 1.02-1.12]) were associated with reductions in PA. In subgroup analysis among breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms, self-reported lower extremity joint pain (OR = 1.23 [95% CI: 1.00-1.50]) and impaired lower extremity physical function (OR = 1.07 [95% CI: 1.01-1.14]) were associated with reductions in PA. Breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms were more likely to report reductions in PA since initiating aromatase inhibitor therapy compared with those without aromatase inhibitor associated musculoskeletal symptoms. Our findings suggest that tailored interventions targeting lower extremity functional limitations are needed to enable breast cancer survivors with aromatase inhibitor associated musculoskeletal symptoms to participate in PA.


Parameatal urethral cyst in a 9-year-old boy.
Parameatal urethral cyst (PUC) is a comparatively unusual pathology in children. Since its first report, approximately 100 cases have been reported in the literature, mostly in the Japanese population. We report such a case in a 9-year old boy who presented with urine stream distortion, successfully managed by complete excision of the cyst, with total removal of the epithelium, which is the treatment of choice to prevent recurrence.


Activation of adenomatous polyposis coli (APC) gene expression by the DNA-alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine requires p53.
Development of colon cancer is a multistep process frequently involving mutations in both the APC and p53 tumor suppressor genes. In this study we treated the HCT-116 colon cancer cell line with alkylating agents including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG),which is known to cause colon cancer in animals, and examined the expression of both APC and p53 genes. Exposure of cells with MNNG caused an 8-12-fold increase in the level of APC mRNA and protein. APC induction was shown to result from increased nuclear transcription of the APC gene and correlated with a concomitant increase in the p53 protein level after MNNG treatment. A necessary role for p53 in APC gene regulation is supported by the failure of MNNG to induce APC expression in cell lines either expressing very low levels of p53 (HeLa cells) or no p53 (K562 erythroleukemia cells). The overexpression of wild-type p53 gene into HCT-116 cells mimicked the effect of MNNG-induced expression of APC mRNA. A direct causal role for p53 in APC gene regulation was further evaluated by transfecting the wild-type p53 gene into K562 cells and observing a 5-fold increase in the APC gene expression. These results support a model featuring a direct link between p53 and APC in response to alkylation-induced DNA damage and suggest a novel role for p53 in a stress-response pathway involving APC.


Light-mediated Activation of Nitrate Reductase in Synchronous Chlorella.
The mechanism underlying the sharp increase in activity of nitrate reductase (EC 220.127.116.11) in Chlorella vulgaris forma tertia (strain 211 8k) during the first hour of the 7 hours/5 hours light/dark cycle was investigated. Using the method of density labeling and isopycnic centrifugation, it could be demonstrated that this rapid increase in activity is based on light-mediated activation rather than de novo synthesis of the enzyme. The problematic nature of cycloheximide specificity and models of nitrate reductase activation are discussed.


Huntington's Chorea in South Wales. A genetic and epidemiological study.
A study of Huntington's Chorea in South Wales has shown a prevalence of 7.61 per 100,000 in the counties of Gwent and Glamorgan, with a total population of 1.7 million. Heterozygote frequency is close to 1 in 5,000. Total ascertainment within this area has been attempted, and experience since conclusion of the study has shown no patients who have been omitted apart from those originating outside the area and those new cases with no living affected relatives. Analysis of migration patterns suggests that around 20% of cases in each generation arise from outside Glamorgan and Gwent and that around 12% of first-degree relatives of indigenous cases have left the area. The survey has formed the initial phase of a long-term prospective study of the disease involving systematic genetic counselling of all high-risk individuals and regular surveillance to monitor possible trends in future prevalence.


Parent Involvement in Adolescent Obesity Treatment: A Systematic Review.
Family-based lifestyle interventions are recommended for adolescent obesity treatment, yet the optimal role of parents in treatment is unclear. To examine systematically the evidence from prospective randomized controlled and/or clinical trials (RCTs) to identify how parents have been involved in adolescent obesity treatment and to identify the optimal type of parental involvement to improve adolescent weight outcomes. Data sources included PubMed, PsychINFO, and Medline (inception to July 2019). RCTs evaluating adolescent (12-18 years of age) obesity treatment interventions that included parents were reviewed. Studies had to include a weight-related primary outcome (BMI and BMI z score). Eligible studies were identified and reviewed, following the Preferred Reporting for Systematic Review and Meta-Analyses guidelines. Study quality and risk of bias were evaluated by using the Cochrane Collaboration risk of bias tool. This search identified 32 studies, of which 23 were unique RCTs. Only 5 trials experimentally manipulated the role of parents. There was diversity in the treatment target (parent, adolescent, or both) and format (group sessions, separate sessions, or mixed) of the behavioral weight loss interventions. Many studies lacked detail and/or assessments of parent-related behavioral strategies. In ∼40% of unique trials, no parent-related outcomes were reported, whereas parent weight was reported in 26% and associations between parent and adolescent weight change were examined in 17%. Only RCTs published in English in peer-reviewed journals were eligible for inclusion. Further research, with detailed reporting, is needed to inform clinical guidelines related to optimizing the role of parents in adolescent obesity treatment.


Methods of Modification of Mesenchymal Stem Cells and Conditions of Their Culturing for Hyaline Cartilage Tissue Engineering.
The use of mesenchymal stromal cells (MSCs) for tissue engineering of hyaline cartilage is a topical area of regenerative medicine that has already entered clinical practice. The key stage of this procedure is to create conditions for chondrogenic differentiation of MSCs, increase the synthesis of hyaline cartilage extracellular matrix proteins by these cells and activate their proliferation. The first such works consisted in the indirect modification of cells, namely, in changing the conditions in which they are located, including microfracturing of the subchondral bone and the use of 3D biodegradable scaffolds. The most effective methods for modifying the cell culture of MSCs are protein and physical, which have already been partially introduced into clinical practice. Genetic methods for modifying MSCs, despite their effectiveness, have significant limitations. Techniques have not yet been developed that allow studying the effectiveness of their application even in limited groups of patients. The use of MSC modification methods allows precise regulation of cell culture proliferation, and in combination with the use of a 3D biodegradable scaffold, it allows obtaining a hyaline-like regenerate in the damaged area. This review is devoted to the consideration and comparison of various methods used to modify the cell culture of MSCs for their use in regenerative medicine of cartilage tissue.


The excretion of theobromine in Thoroughbred racehorses after feeding compounded cubes containing cocoa husk--establishment of a threshold value in horse urine.
Thoroughbred geldings were fed racehorse cubes containing a predetermined concentration of theobromine in the form of cocoa husk. They were offered 7 kg of cubes per day, divided between morning and evening feed, and food consumption was monitored. Urinary concentrations of theobromine were determined following the consumption of cubes containing 11.5, 6.6, 2.0 and 1.2 mg per kg of theobromine, to verify whether or not such concentrations would produce positive urine tests. Pre-dose urine samples were collected to verify the absence of theobromine before each experiment. It became apparent from the results of the first three administrations that the limit of detection of theobromine, using such procedures, would be reached at a feed level of about 1 mg per kg theobromine. Therefore the final administration, using cubes containing 1.2 mg per kg theobromine, was singled out for additional analytical work and quantitative procedures were developed to measure urinary concentrations of theobromine. It was anticipated that the results would form a basis for discussions relating to the establishment of a threshold value for theobromine in horse urine. The Stewards of the Jockey Club subsequently gave notice that they had established a threshold level for theobromine in urine of 2 micrograms/ml.


A new system for a combined laser and ultrasound application in neurosurgery.
A new combined Laser and Ultrasound Surgical Therapy (LUST) device suitable for endoscopical coagulation and tissue fragmentation has been developed at the LMTB. The new feature is the simultaneous transmission of laser radiation and ultrasound via flexible silica glass fibers. The ultrasound tissue interaction is based on the well-known CUSA-technology which enables the surgeon to cut various types of tissue with different degrees of effectiveness. Application fields are in oncology, neurosurgery and angioplasty. The laser radiation can be used, for example, for tissue coagulation purposes. With a fiber based LUST-system working at a frequency of 30 kHz, a displacement of 100 microns could be attained at the distal end. (The usual standard CUSA displacement is 10-350 microns.) During in vitro experiments the following tissue fragmentation rates could be achieved: brain tissue 50 mg sec-1, liver 4.5 mg sec-1 and kidney 4 mg sec-1 (displacement of the tip 60 microns; phi 1.3 mm; suction setting: 5 W). Laser radiation up to 25 W was sufficient to coagulate soft tissue. This technology offers new possibilities in minimal invasive surgery. The flexible opto-acoustic waveguide (phi 400-1700 microns) can be bent making areas accessible that were previously inaccessible. Without changing the instrumentation the surgeon can use the laser radiation for tissue coagulation or cutting and the ultrasound for tissue fragmentation and tissue reduction.


Court-mandated outpatient psychiatric care for a pregnant woman with psychosis: a unique bridge to alliance.
We describe the case of a young pregnant woman with refractory schizoaffective disorder and how we reached a decision to apply for court-mandated outpatient psychiatric treatment (Assisted Outpatient Treatment or AOT). The patient was stable when we made this application as a preventive measure, given her serious prior episodes of illness. While there has been court-mandated outpatient obstetrical treatment, as far as we know this is the first report of mandated outpatient psychiatric treatment in connection with pregnancy. The ultimate benefit of this AOT application was the development of a therapeutic alliance and improved voluntary adherence to treatment, and a safe outcome to the pregnancy.


[Comparative evaluation of 3 leukocyte filters for thrombocyte concentrates].
Several polyester adsorption filters are available for the removal of leukocytes during bedside filtration of platelet concentrates (PC). We tried to evaluate the efficacy of three leukocyte filters: PL-100 (Pall, USA), Sepacell PL-5A and PL-10A (both Asahi, Japan) using single donor PCs. All filters were used according to the manufacturer's instructions. The main difference in handling is the recommendation of priming and rinsing the Asahi filters with saline. Platelet counts were performed by an automatic cell counter, leukocyte (WBC) counts using a modified chamber method. Biocompatibility was examined by assessing anaphylatoxin, PMN-elastase and LDH levels, platelet function by measuring induced aggregation, hypotonic shock response, beta-thromboglobulin levels and the mean platelet volume. According to the different initial WBC contamination, three groups of PCs were tested. Group I and II were processed one hour after apheresis. Group III (n = 30) was stored at 12 degrees C up to five days before filtration. Function and integrity of post-filtration platelets were not affected as compared to the prefiltration status and bioincompatibility could not be detected. Our results indicate that the WBC reduction capacity of the filters is related to the initial WBC contamination of the PC. Beyond an initial contamination of 10(9) WBC, none of the filters is capable of reducing the leukocyte count below 10(6) WBC/PC. All but PL-5A reduce the WBC reliably below 10(6)/PC as determined from PCs routinely prepared. The Asahi filters cause significantly less platelet loss apparently due to the suggested postfiltration rinsing. Storage of PC does not influence the WBC reduction capacity, however increases the platelet loss for the PL-100.


[Premedication with H1- and H2-receptor antagonists for intravenous urography using contrast media].
Intravenous urography using Telebrix was performed on 500 patients. Two hundred patients (group I) received no pre-medication; 300 patients (group II) were premedicated with H1 and H2 receptor antagonists. All patients were examined for signs of contrast reactions, blood pressure, pulse rate and plasma histamine levels. These were measured before and three minutes after the administration of the antihistamine substances and/or the contrast medium, and also at the end of the examination. Following the administration of H1 and H2 receptor antagonists, a slight, transient and insignificant rise in plasma histamine could be demonstrated. Both groups showed a significant rise in plasma histamine levels after the injection of the contrast medium. Although the pre-medicated group contained a higher percentage of high risk patients, there were significantly fewer patients with contrast reactions. Pre-medication with H1 and H2 receptor antagonists in high risk patients is therefore advisable.


Medication safety in hospitals.
Medication error and adverse drug reactions occur frequently, leading to a high burden of patient harm in the hospital setting. Many Irish hospitals have established medication safety initiatives, designed to encourage reporting and learning to improve medication use processes and therefore patient safety. Eight Irish hospitals or hospital networks provided data from voluntary medication safety incident and near miss reporting programmes for pooled analysis of events occurring between 1st January 2006 and 30th June 2007. 6179 reports were received in total (mean 772 per hospital; range 96-1855). 95% of reports did not involve patient harm. Forty seven percent of reports related to the prescribing stage of the medication use process, 40% to the administration stage and 9% to the pharmacy dispensing stage. This data is published to increase awareness of this key patient safety issue, to share learning from these incidents and near misses and to encourage a more open patient safety culture.


Occurrence of Campylobacter jejuni in Gulls Feeding on Zagreb Rubbish Tip, Croatia; Their Diversity and Antimicrobial Susceptibility in Perspective with Human and Broiler Isolates.
Campylobacteriosis is the most common gastrointestinal bacterial disease in the European Union (EU). Wild birds are one of the natural reservoirs of these pathogens. In this study we tested cloacal swabs of 643 gulls captured on rubbish tip in Zagreb, Croatia for the presence of Campylobacter spp. and found 168 Campylobacter positive samples. We used multilocus sequence typing (MLST) to genotype 62 random C. jejuni isolates from gulls, 24 isolates from broiler caeca, 27 isolates from broiler neck skins and 23 human isolates. Altogether, we identified 44 different STs, from which 19 were newly described. Most of the new STs (14) originate from gulls. Although humans and broilers share the majority of STs and isolates from gulls are separated from these, there was one ST present in all three hosts: 45. Additionally antimicrobial susceptibility to six antimicrobials was performed on 123 C. jejuni strains isolated from broiler caeca (n = 22), neck skins of broilers (n = 20), gulls cloacal swabs (n = 50) and human faeces (n = 31) by the broth microdilution method. Results show lower resistance of gull isolates to NAL and CIP, while resistance to TET was as high as in human and broiler isolates.


Altered apoptosis/autophagy and epigenetic modifications cause the impaired postimplantation octaploid embryonic development in mice.
Polyploids are pervasive in plants and have large impacts on crop breeding, but natural polyploids are rare in animals. Mouse diploid embryos can be induced to become tetraploid by blastomere fusion at the 2-cell stage and tetraploid embryos can develop to the blastocyst stage in vitro. However, there is little information regarding mouse octaploid embryonic development and precise mechanisms contributing to octaploid embryonic developmental limitations are unknown. To investigate the genetic and epigenetic mechanisms underlying octaploid embryonic development, we generated mouse octaploid embryos and evaluated the in vitro/in vivo developmental potential. Here we show that octaploid embryos can develop to the blastocyst stage in vitro, but all fetus impaired immediately after implantation. Our results indicate that cell lineage specification of octaploid embryo was disorganized. Furthermore, these octaploid embryos showed increased apoptosis as well as alterations in epigenetic modifications when compared with diploid embryos. Thus, our cumulative data provide cues for why mouse octaploid embryonic development is limited and its failed postimplantation development.


Special adaptive recreation as intervention in vocational and transitional services for handicapped youth.
Increased concern for rising costs of disability-related programs, coupled with various manpower and economic projections, have resulted in major shifts in federal program priorities. The shift from institutional support to "self-help programs" mandates service providers to demonstrate the extent to which their programs promote independent living skills among the handicapped. As a result of recent and projected trends, leisure service providers must begin to articulate and justify their roles as essential to vocational training and successful placement of handicapped individuals within the community. The purpose of this article is to present a Special Adaptive Recreation Support Systems Model, which demonstrates the utilization of special recreation programs as a supportive service to educational, vocational, transitional, and community programs for the handicapped.


In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX-CreERT2 mice.
To study the function of individual neurons that are embedded in a complex neural network is difficult in mice. Conditional mutagenesis permits the spatiotemporal control of gene expression including the ablation of cells by toxins. To direct expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2) selectively to cortical neurons, we replaced the coding region of the murine Nex1 gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When injected with tamoxifen, adult NEX-CreERT2 mice induced reporter gene expression exclusively in projection neurons of the neocortex and hippocampus. By titrating the tamoxifen dosage, we achieved recombination in single cells, which allowed multiphoton imaging of neocortical neurons in live mice. When hippocampal projection neurons were genetically ablated by induced expression of diphteria toxin, within 20 days the inflammatory response included the infiltration of CD3+ T cells. This marks a striking difference from similar studies, in which dying oligodendrocytes failed to recruit cells of the adaptive immune system.


Clinical Features of Patients Presenting to the Emergency Department With Cardiovascular Adverse Reactions After COVID-19 mRNA Vaccination.
Since the implementation of the nationwide coronavirus disease 2019 (COVID-19) vaccination campaign, emergency departments (EDs) have had an increasing number of patients reporting postvaccination cardiovascular adverse effects. We investigated the clinical features of patients who visited the ED for cardiovascular adverse reactions after COVID-19 mRNA vaccination. We conducted a retrospective observational study in two EDs. Patients with cardiovascular adverse reactions after COVID-19 mRNA vaccination who visited EDs between June 1, 2021, and October 15, 2021, were selected. The clinical data of these patients were collected by reviewing medical records. Among 683 patients, 426 (62.4%) were female. The number of patients in their 20s was the highest (38.9% of males, 28.2% of females) (P < 0.001). More patients visited the ED for adverse reactions following the first vaccine dose than following the second dose (67.6% vs. 32.2%). Chief complaints were chest pain/discomfort (74.4%), dyspnea (14.3%) and palpitation (11.3%). The final diagnosis was a nonspecific cause (63.1%), and 663 (97.1%) patients were discharged from the ED. The admission rate was higher in males than in females (3.9% vs. 1.9%). Myocarditis was diagnosed in four males, who showed mild clinical progression and were discharged within 5 hospital days. Most patients who visited the ED with cardiovascular adverse reactions were discharged from the ED, but some were admitted for other medical diseases as well as adverse vaccine reactions. Therefore, further surveillance and a differential diagnosis of cardiovascular adverse events after COVID-19 mRNA vaccination should be considered by emergency physicians.


Examining Factors of Engagement With Digital Interventions for Weight Management: Rapid Review.
Digital interventions for weight management provide a unique opportunity to target daily lifestyle choices and eating behaviors over a sustained period of time. However, recent evidence has demonstrated a lack of user engagement with digital health interventions, impacting on the levels of intervention effectiveness. Thus, it is critical to identify the factors that may facilitate user engagement with digital health interventions to encourage behavior change and weight management. The aim of this study was to identify and synthesize the available evidence to gain insights about users' perspectives on factors that affect engagement with digital interventions for weight management. A rapid review methodology was adopted. The search strategy was executed in the following databases: Web of Science, PsycINFO, and PubMed. Studies were eligible for inclusion if they investigated users' engagement with a digital weight management intervention and were published from 2000 onwards. A narrative synthesis of data was performed on all included studies. A total of 11 studies were included in the review. The studies were qualitative, mixed-methods, or randomized controlled trials. Some of the studies explored features influencing engagement when using a Web-based digital intervention, others specifically explored engagement when accessing a mobile phone app, and some looked at engagement after text message (short message service, SMS) reminders. Factors influencing engagement with digital weight management interventions were found to be both user-related (eg, perceived health benefits) and digital intervention-related (eg, ease of use and the provision of personalized information). The findings highlight the importance of incorporating user perspectives during the digital intervention development process to encourage engagement. The review contributes to our understanding of what facilitates user engagement and points toward a coproduction approach for developing digital interventions for weight management. Particularly, it highlights the importance of thinking about user-related and digital tool-related factors from the very early stages of the intervention development process.


"Pseudo reinfarction": a consequence of electrocardiogram lead transposition following myocardial infarction.
Unexpected or bizarre new electrocardiographic changes should alert the physician to the possibility of lead transposition and, if in doubt, the electrocardiogram should be repeated. The classic form of limb lead transposition leading to the appearance of dextrocardia is well recognized. We report a patient with myocardial infarction where lead transposition led to a diagnosis of reinfarction and to the inappropriate use of thrombolytic therapy.


[Tumor-specific expression of PBOV1, a new gene in evolution].
We identified mRNA of the newly discovered gene PBOV1 in a multitude of samples from tumors of the brain, lung, liver, gallbladder, colon, small intestine, mammary gland, uterus, ovary, ureter, adrenals, parotid, thymus and spleen. However, out of 29 intact adult and 8 fetal tissues, only pancreas was characterized by weak expression of the gene. Our results demonstrated that the PBOV1 gene expression is tumor-specific and has a potential as tumor marker. It is worth mentioning that we had predicted that property on the basis of available evolutionary data.


Interregional migration in the U.S.S.R., 1981-1985 and 1971-1975.
"The publication in 1987 of a Soviet compendium of population statistics has made possible the calculation of net migration balances for the U.S.S.R.'s 20 large economic planning regions.... This paper compares the results for 1981-1985 and 1971-1975 and finds that Siberia has changed from a net loser to a net gainer of migrants, that the shift of population to the southern regions has been reversed, and that the traditional rural outflow from central-eastern European Russia has diminished. Nevertheless, the acclimatization of newcomers in the eastern regions, the stabilization of rural dwellers in the central regions, and the mobility of rural residents in Central Asia and the Transcaucasus all remain insufficient to overcome regional imbalances in labour." (SUMMARY IN FRE)


Central serotonin neurons are required for arousal to CO2.
There is a long-standing controversy about the role of serotonin in sleep/wake control, with competing theories that it either promotes sleep or causes arousal. Here, we show that there is a marked increase in wakefulness when all serotonin neurons are genetically deleted in mice hemizygous for ePet1-Cre and homozygous for floxed Lmx1b (Lmx1b(f/f/p)). However, this only occurs at cool ambient temperatures and can be explained by a thermoregulatory defect that leads to an increase in motor activity to generate heat. Because some serotonin neurons are stimulated by CO(2), and serotonin activates thalamocortical networks, we hypothesized that serotonin neurons cause arousal in response to hypercapnia. We found that Lmx1b(f/f/p) mice completely lacked any arousal response to inhalation of 10% CO(2) (with 21% O(2) in balance N(2)) but had normal arousal responses to hypoxia, sound, and air puff. We propose that serotonin neurons mediate the potentially life-saving arousal response to hypercapnia. Impairment of this response may contribute to sudden unexpected death in epilepsy, sudden infant death syndrome, and sleep apnea.


Outcome in adolescent idiopathic scoliosis after brace treatment and surgery assessed by means of the Scoliosis Research Society Instrument 24.
A retrospectively designed long-term follow-up study of adolescent idiopathic scoliosis (AIS) patients who had completed treatment, of at least 2 years, by means of brace, surgery, or both brace and surgery. This study is to assess the outcome after treatment for AIS by means of the Scoliosis Research Society Outcome Instrument 24 (SRS 24). One hundred and eighteen AIS patients (99 females and 19 males), treated at the Aarhus University Hospital from January 1, 1987 to December 31, 1997, were investigated with at least 2 years follow-up at the time of receiving a posted self-administered questionnaire. Forty-four patients were treated with Boston brace (B) only, 41 patients had surgery (S), and 33 patients were treated both with brace and surgery (BS). The Cobb angles of the three treatment groups did not differ significantly after completed treatment. The outcome in terms of the total SRS 24 score was not significantly different among the three groups. B patients had a significantly better general (not treatment related) self-image and higher general activity level than the total group of surgically treated patients, while surgically treated patients scored significantly better in post-treatment self-image and satisfaction. Comparing B with BS we found a significantly higher general activity level in B patients, while the BS group had significantly higher satisfaction. There were no significant differences between BS and S patients in any of the domain scores. All treatment groups scored "fair or better" in all domain scores of the SRS 24 questionnaire, except in post-treatment function, where all groups scored worse than "fair". Improvement of appearance by means of surgical correction increases mean scores for post-treatment self-image and post-treatment satisfaction. Double-treatment by brace and surgery does not appear to jeopardize a good final outcome.


The heroines of their own stories: Insights from the use of life history drawings in research with a transnational migrant community.
In this paper, we discuss how life history drawings can serve as a valuable method for global health research. The introduction discusses qualitative approaches to concepts such as reliability, validity and triangulation, and situates the use of participatory visual methods within the broader field of participatory research. The paper reports on an experience using life history drawings as part of extended ethnographic research in rural Mexico and among Mexican migrants living in Atlanta. The primary method for that parent project was comparative ethnographic research, which included life histories collected from 13 pairs of women over 15 months of participant observation. Early in the research, the drawings contributed to a major reorientation in the direction of the research project. The insights generated through analysis of the life history drawings exemplify how this participatory research technique can direct attention to social processes that feel salient to community members. In this case, they called attention to the enormity of social change in this community over one generation, reorienting the study from one focused on change causes by migration to one that focused on two trajectories of change: generational and migration-related.


Surface and Spectroscopic Properties of Acetylcholinesterase Monolayer at the Air/Water Interface
The behavior of the enzyme acetylcholinesterase was studied at the air/water interface. Surface pressure-area (pi-A) isotherms and UV-vis spectra recorded at different surface pressures were determined for different salt concentrations in the subphase. The ionic strength of the subphase does not influence the physical properties in consideration; however, the pH of the subphase has a great effect on its surface and optical properties. A subphase at pH 6.5 has shown that the enzyme is highly stable, based on the pi-A compression/decompression isotherms. No changes in the area per molecule were observed when the surface pressure was maintained constant at 16 mN/m for a period of 120 min. The long-term stability of acetylcholinesterase at the air/water interface was demonstrated for pH 6.5 and a salt concentration of 10(-2) M (KCl). The absorption spectra of the monolayer, measured directly at the air/water interface, are considered good evidence of the organization of the enzyme molecules. Copyright 1997 Academic Press. Copyright 1997Academic Press


Evidence for pervasive adaptive protein evolution in wild mice.
The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans.


Addiction: a journal and its Invisible College.
PROVENANCE: This paper derives from a lecture given before the Society for the Study of Addiction in November 2004, on the author's retirement from the position of Editor-in-Chief of Addiction, one of the Society's journals. To identify the live processes which have influenced the journal's evolution since its foundation in 1884. Over the 120-year period a strong, continuing historical thread has been the fluctuating success of the journal's engagement with its 'Invisible College', the community which it seeks to serve. It is argued that the journal's future success will depend on its capacity to explore and nurture further this two-way relationship. Addiction is a journal with an active and clearly articulated, multiple vision of it purpose, and this vision is outlined. It dares to try to influence its future with the authority so to do rooted in its ability to reflect the aspirations and concerns of its readers. It is 'a journal of the second kind'.


EBV-encoded RNA via TLR3 induces inflammation in nasopharyngeal carcinoma.
Pathogen-induced inflammation has been one of the intensive research areas in carcinogenesis. EBV encoded RNAs (EBERs) have been suggested to play roles in anti-apoptosis and growth-promotion in lymphoid and immune disorders. However, pathological roles of EBERs in solid tumors of epithelia origin remain to be elucidated. Given their characteristic dsRNA structures, recent studies provided evidences for the activation of some pattern recognition receptors (PRR) by EBERs, which is fundamental in the process of pathogenesis. Here, we show that EBERs induce inflammatory response in nasopharyngeal carcinoma (NPC) cells through Toll-like receptor 3 (TLR3), mainly featured by high level of TNFα production. Interestingly, EBERs and EBV latent membrane protein 1 (LMP1) form a positive regulatory loop with NF-κB as a key node that amplifies the inflammatory signals in EBV infected epithelial cells. We demonstrate in vivo that EBERs can interact with TLR3 and induce tumor cells to produce cytokines in B16 synergetic tumor and human NPC xenograft models, in which macrophages are recruited and activated, leading to a favorable microenvironment for solid tumor growth. Lastly, we verify a positive association between EBER and TNFα levels in NPC clinical samples and the combination of EBER and TNFα expressions provides a predictor of poor survival of NPC patients. In conclusion, EBERs play a pivotal role in inflammation-to-oncogenesis transition in NPC development.


Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats.
Processed aconite root (PA), the root of Aconitum carmichaeli (Ranunculaceae), is a crude drug used in traditional Chinese or Japanese kampo medicine to treat pain associated with coldness. In our previous study, PA and its active ingredient, neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice. The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients. PA powder (1 g/kg/day) was orally administered, and either neoline or benzoylmesaconine (10 mg/kg/day) was subcutaneously injected into the murine model. Mechanical hyperalgesia was evaluated via the von Frey filament method. PA extract was orally administered to rats; blood samples were chronologically collected, and the plasma concentrations of Aconitum alkaloids were measured. The contents of Aconitum alkaloids in commercial PA products were also measured. PA extract and neoline significantly attenuated the mechanical hyperalgesia induced by either paclitaxel or partial ligation of the sciatic nerve in mice. In the plasma samples of rats treated with PA extract, higher concentrations of benzoylmesaconine and neoline were apparent among Aconitum alkaloids. The contents of benzoylmesaconine and neoline varied among PA products with different processing procedures. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia induced by each paclitaxel, partial ligation of the sciatic nerve, or oxaliplatin in mice. The present results indicate that PA and its active ingredient, neoline, are promising agents for the alleviation of neuropathic pain. Neoline can be used as a marker compound to determine the quality of the PA products for the treatment of neuropathic pain.


Adult attachment processes: individual and couple perspectives.
This paper overviews a new approach to understanding the range of difficulties experienced in close attachment relationships in adulthood. Drawing on the work of Bowlby, four prototypic adult attachment patterns are defined in terms of the intersection of two underlying dimensions, the positivity of the person's self-image and the positivity of the person's image of others (Bartholomew, 1990; Bartholomew & Horowitz, 1991). The distinct interpersonal difficulties associated with each attachment pattern are described. Findings are presented indicating that individual differences in attachment have implications for the quality of adults' romantic relationships, and that attachment theory may be helpful in understanding violent spousal relationships. Five current issues in the study of adult attachment are addressed: the stability of attachment patterns, the associations between attachment and general personality factors, the relative merits of categorical and prototype assessments of attachment, the identification of multiple attachments in adulthood, and the specificity of adult attachment patterns. It is suggested that the four-category model of adult attachment is especially sensitive to the range and complexity of attachment-related difficulties experienced in adulthood.


Ancient remains and the first peopling of the Americas: Reassessing the Hoyo Negro skull.
A noticeably well-preserved ∼12.500 years-old skeleton from the Hoyo Negro cave, Yucatán, México, was recently reported, along with its archaeological, genetic and skeletal characteristics. Based exclusively on an anatomical description of the skull (HN5/48), Chatters and colleagues stated that this specimen can be assigned to a set of ancient remains that differ from modern Native Americans, the so called "Paleoamericans". Here, we aim to further explore the morphological affinities of this specimen with a set of comparative cranial samples covering ancient and modern periods from Asia and the Americas. Images published in the original article were analyzed using geometric morphometrics methods. Shape variables were used to perform Principal Component and Discriminant analysis against the reference samples. Even thought the Principal Component Analysis suggests that the Hoyo Negro skull falls in a subregion of the morphospace occupied by both "Paleoamericans" and some modern Native Americans, the Discriminant analyses suggest greater affinity with a modern Native American sample. These results reinforce the idea that the original population that first occupied the New World carried high levels of within-group variation, which we have suggested previously on a synthetic model for the settlement of the Americas. Our results also highlight the importance of developing formal classificatory test before deriving settlement hypothesis purely based on macroscopic descriptions.


Several physical properties of aflatoxin-contaminated pistachio nuts: application of BGY fluorescence for separation of aflatoxin-contaminated nuts.
The primary objective was to evaluate and find a proper method for visual identification of aflatoxin-contaminated pistachio nuts. The feasibility of using bright greenish yellow fluorescence (BGYF) in pistachio nut as a discriminating factor for identification of Aspergillus flavus-infested nuts, at harvest and in post-harvest, is investigated. Results show a strong relationship between BGYF and aflatoxin content at harvest. The factors affecting the application of this method in post-harvest stages are also discussed. The relationship between inside-brown kernels and aflatoxin presence is confirmed. At harvest, the brown kernels are a subdivision of fluorescent fraction. The share of different pistachios based on hull types (with sound hull, growth split and early-split) in contamination is studied. The early-split nuts are the most contaminated nuts, growth split nuts are less contaminated, and pistachios with sound hulls are almost clean. The effect of inappropriate handling on the percentage of fluorescent nuts is studied. The percentage of visible mould in samples is observed which shows a good relationship with the presence of BGY fluorescence.


Transcriptional repression of the yeast CHA1 gene requires the chromatin-remodeling complex RSC.
In eukaryotes, DNA is packaged into chromatin, a compact structure that must be disrupted when genes are transcribed by RNA polymerase II. For transcription to take place, chromatin is remodeled via nucleosome disruption or displacement, a fundamental transcriptional regulatory mechanism in eukaryotic organisms. Here we show that the yeast chromatin-remodeling complex, RSC (remodels the structure of chromatin), isolated on the basis of homology to the SWI/SNF complex, is required for proper transcriptional regulation and nucleosome positioning in the highly inducible CHA1 promoter. In the absence of Sth1p/Nps1p (a homolog of Swi2p/Snf2p) or of Swh3p (a homolog of Swi3p), expression of CHA1 in non-induced cells is increased to a level comparable with that of fully induced cells. Furthermore, in non-induced cells depleted for Sth1p/Nps1p or Swh3p, a nucleosome positioned over the TATA box of the CHA1 promoter is disrupted, an architectural change normally only observed during transcriptional induction. In addition, deletion of the gene-specific activator Cha4p did not affect derepression of CHA1 in cells depleted for Swh3p. Thus, CHA1 constitutes a target for the RSC complex, and we propose that RSC is essential for maintaining a repressive chromatin structure at the CHA1 promoter.


Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.
The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs.


Demonstration of antibody and cellular immune response to brain extract in West and Lennox-Gastaut syndromes.
We investigated humoral and cellular immune response to brain tissues in 15 patients with West syndrome, in 9 patients with Lennox-Gastaut syndrome and in 20 healthy children. High levels of a precipitating antibody to a saline extract of brain tissue were detected in all patients; leucocyte migration inhibition test with the same antigen was found to be positive in most of them. The role of this autoimmune response in the pathogenesis of West and Lennox-Gastaut syndromes remains to the elucidated.


Stress, aging and reliability of antioxidant enzyme defense.
Clinical and experimental data point to existence of disturbances of adaptive ability of aged organism to extreme impacts. However mechanisms of these disturbances are not clear yet. The purpose of the investigation was to study age-related changes in reaction of erythrocyte antioxidant enzyme system in response to acute psycho-emotional stress and a possible role of these changes in age-related alterations of oxygen blood transport in nonhuman primates. Ten young (6-8 years) and ten old (20-26 years) healthy female rhesus monkeys were subjected to acute moderate psycho-emotional stress (two hours squeeze cage restraint) at 1500h. Plasma cortisol, lipid peroxidation products (TBARS) and activities of superoxide dismutase (SOD), glutathione peroxidase, gluthatione reductase (GR), and gluthatione-S-transferase in erythrocytes were measured before stress and at 30, 60, 120, 240 min and 24 hours after beginning of the stress. We have found for the first time that SOD activity decreased in response to the stress in young monkeys while it increased in the half of old monkeys. Young animals also demonstrated essentially higher increase in GR activity and plasma cortisol level in response to the restraint in comparison with old monkeys. Level of TBARS did not practically change in response to the stress in young animals and significantly increased in old monkeys. The study demonstrated that the age-related alterations in SOD and GR stress responsiveness lead to activation of peroxide oxidation of lipids that may be considered as an important factor of aging damage of erythrocyte functioning and reliability of oxygen transport to tissues under stress conditions.


Hematopoietic recovery in a patient with acute lymphoblastic leukemia after an autologous marrow graft purged by combined hyperthermia and interferon in vitro.
We describe a patient with acute lymphoblastic leukemia (ALL) in whom hemopoiesis recovered after an autologous marrow graft purged by in vitro hyperthermia. A 17-year-old woman was diagnosed as having ALL in April 1985. After clinical remission was induced, marrow cells were harvested. The marrow cells were treated with hyperthermia at 42.0 degrees C for 1 h in the presence of alpha-interferon to eliminate residual leukemic cells, and then cryopreserved. In January 1990, during her fourth remission she was treated with busulfan and cyclophosphamide, and then received the thawed autologous marrow. Her hematopoietic recovery was prompt with normal trilineage regeneration without any life-threatening complications. She is in good health without evidence of a leukemic relapse at 6 months after autologous bone marrow transplantation. This case suggests that human multilineage progenitor cells retain self-renewal capacity in vivo even after treatment with heat and alpha-interferon in vitro followed by the freezing and thawing procedures.


How to Eliminate a Deficit-Centered Mindset About Medical Students of Color.
Approaches to responding to racial and ethnic health inequity in the United States have had limited impact over the past 40 years. Efforts to increase the number of medical students of color are undermined by hyperfocus and overreliance on and misinterpretation and misuse of standardized examination scores. Structural racism and persistence of deficit-focused interventions undermine appreciation of the value that students and physicians with minoritized identities bring to medicine and to US health care's systemic capacity to motivate equity.


Utility of 18F-fluorodeoxyglucose positron emission tomography for distinguishing between the histological types of early stage thymic epithelial tumours.
Recent studies have shown the usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating between World Health Organization (WHO) histological subgroups of thymic epithelial tumours. However, these reports may have included many advanced cases of these lesions (Masaoka stage III or IV) of high-risk subtypes. The objective of our present study was to assess the usefulness of FDG-PET for distinguishing the histological subtypes of early stage thymic epithelial tumours (Masaoka stage I or II). Twenty patients who had undergone an FDG-PET examination prior to treatment and had been diagnosed with an early stage thymic epithelial tumour between July 2005 and July 2011 were enrolled in the present study. All patients underwent a total thymectomy. This cohort was divided into two groups according to the WHO histological classification of their lesion, i.e. low-risk tumours (types A, AB or B1) in one group and high-risk tumours (types B2, B3 or thymic carcinoma) in the other. Focal FDG accumulation was evaluated by determining the maximum standardized uptake value (SUV-max). The patient cohort for this study included 13 men and 7 women ranging in age from 26 to 70 years (mean 55 years). The low-risk group included seven cases (type A, 0; type AB, 7; type B1, 0), and the high-risk group comprised 13 cases (type B2, 7; type B3, 3; thymic carcinoma, 3). The SUV-max values of the low-risk and high-risk tumours were 3.09 ± 0.51 and 6.19 ± 3.13, respectively, and this was a significant difference. For the differential diagnosis of low-risk and high-risk tumours, sensitivity and specificity were 92.3% and 83.3%, respectively, when an SUV-max of 3.5 was used as a cutoff. FDG-PET is a useful method for distinguishing histological types of early stage thymic epithelial tumours.


Determination of organophosphorus pesticides by capillary electrophoresis-inductively coupled plasma mass spectrometry with collective sample-introduction technique.
A new method for the determination of organophosphorus pesticides using CE-ICP-MS with collective sample-introduction technique has been developed in this study. The method has been successfully used to separate and determine dimethoate, trichlorfon and glyphosate with an RSD of < 5% for migration times (n = 6) and < 4% for peak areas (n = 6). The experimental results showed that the collective sample-introduction considerably reduced the makeup volume and the dilution of analyte, and eventually resulted in a much lower detection limit and a much better electrophoretic resolution. The peak widths and the detection limits of dimethoate, trichlorfon and glyphosate obtained with this method are 15-17 s and 0.05-0.07 microg/mL (as compound), respectively. Using this method, we have successfully separated and determined dimethoate, trichlorfon and glyphosate in vegetable sample with a recovery of 90-96%.


Retooling the Health Care Workforce for an Aging America: A Current Perspective.
A 2008 Institute of Medicine (IoM) report outlined a vision for health care and a workforce capable of addressing health and extended care needs of our aging population. It highlighted dramatic shortages necessitating bold action and outlined recommendations aimed at building a sizable and qualified workforce. This study updates report findings and progress made on its recommendations. Through review of publicly accessible, internet-based literature and government and professional organization websites, current workforce data and recent policy changes are compared to the report's statistics and recommendations. Direct comparisons are limited by changing definitions, context, and data collection and analyses methods. Future workforce-need projections are estimated using reports from various sources. Inability to forecast medical advances, socioeconomic changes, and world events affects the accuracy of these projections. Nonetheless, clear conclusions emerge despite such limitations. Progress toward fulfilling the IoM goals is variable and insufficient. The current and projected numbers for all geriatric health providers remain inadequate compared to estimated 2030 demand. Challenges in meeting estimated needs persist essentially unchanged. The 2008 IoM framework and recommendations remain relevant and constitute an important roadmap to complete unfinished goals. Initial findings from this update provide a platform for developing practice and policy reforms.


Bacteriophage P4 capsid-size determination and its relationship to P2 helper interference.
The sid (size determination) gene product of phage P4 is known to be involved in capsid-size determination. Moreover, the capsid-size determination function interferes with the lytic development of its helper P2, presumably because the helper genome is too large to be packaged into P4-size capsids. In order to study P4-specified helper interference, we cloned the sid gene for expression during phage infection. Even though gpSid restores the capsid-size determination function of a sid defective P4 mutant, we find that gpSid alone is not sufficient to establish full interference of helper P2 phage production. Complete helper interference requires some P4 function in addition to gpSid. Complementation tests show that none of the known P4 genes display this property. We propose that P4 encodes a yet-unidentified function that in concert with gpSid establishes full P2 helper interference at the level of capsid-size determination.


Phenyl-substituted prostaglandins: potent and selective antiglaucoma agents.
A series of phenyl-substituted analogues of prostaglandin F2 alpha (PGF2 alpha) were prepared and evaluated for ocular hypotensive effect and side effects in different animal models. In addition, the activity of the analogues on FP receptors was studied in vitro. The results were compared with those of PGF2 alpha and its isopropyl ester. The phenyl-substituted PGF2 alpha analogues exhibited good intraocular pressure reducing effect, were more selective, and exhibited a much higher therapeutic index in the eye than PGF2 alpha or its isopropyl ester. The analogues exhibited high activity on FP receptors in a stereoselective manner for the 15 alpha-hydroxyl group.


[Timing of administration of granulocyte colony stimulating factor after cytotoxic chemotherapy in hematological malignancies].
We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) given to 30 patients with hematological malignancies after cytotoxic chemotherapy. The first course of chemotherapy was not treated with rhG-CSF (control), and in the second to fourth courses, rhG-CSF was given by one of the following three ways to the patients (not necessarily in this order): 1) 10 days of administration starting 48 hr after chemotherapy, 2) 5 days of administration starting 48 hr after chemotherapy, and 3) 5 days of administration after the leukocyte counts reached to less than 2,000/microliters. The leukocyte nadirs were significantly higher in the course with 10 days of administration compared with the control course. The time needed for recovery from the leukocyte nadir was significantly shorter in 10-day course and 5-day course after the leukocyte counts reached to less than 2,000/microliters. The therapy spans became significantly shorter with all of the three patterns of administration of rhG-CSF compared with the control course. The number of days on which the leukocyte counts became less than 2,000/microliters were significantly fewer in 10-day course and 5-day course after the leukocyte counts became less than 2,000/microliters. These findings showed that rhG-CSF prevented severe neutropenia after cytotoxic chemotherapy, and (or) assisted the rapid recovery from neutropenia. These effects depend on the timing of its administration.


Silage fermentation-updates focusing on the performance of micro-organisms.
Advances in micro-organism identification techniques have resulted in increased knowledge of the diversity of prokaryotes and eukaryotes in silage. Such knowledge has enhanced the understanding of how fermentation occurs in forage crops with different characteristics and how the process can be improved to enhance silage quality. Undesirable micro-organisms can grow in silage when fermentation does not occur properly. Such micro-organisms may be pathogenic and/or produce toxic metabolic compounds; however, information on the consequences of these metabolites on the health of animals that consume silage is still lacking. The major challenge of ensilage is to produce high-quality feed that is nutritional, sanitary and stable, with a high dry matter recovery rate, in a process involving no interventions during fermentation and considerable variation in the characteristics of the substrates. It is important to note that each substrate has particularities and that we can only improve fermentation if we fully understand microbial diversity. This review is intended to update information related to the fermentation profile of silage, focusing on microbial diversity.


Planning for operating room efficiency and faster anesthesia wake-up time in open major upper abdominal surgery.
Reducing anesthesia-controlled time (ACT) may improve operation room (OR) efficiency result from different anesthetic techniques. However, the information about the difference in ACT between desflurane (DES) anesthesia and propofol-based total intravenous anesthesia (TIVA) techniques for open major upper abdominal surgery under general anesthesia (GA) is not available in the literature.This retrospective study uses our hospital database to analyze the ACT of open major upper abdominal surgery without liver resection after either desflurane/fentanyl-based anesthesia or TIVA via target-controlled infusion with fentanyl/propofol from January 2010 to December 2011. The various time intervals including waiting for anesthesia time, anesthesia time, surgical time, extubation time, exit from OR after extubation, total OR time, and postanesthetic care unit (PACU) stay time and percentage of prolonged extubation (≥15 minutes) were compared between these 2 anesthetic techniques.We included data from 343 patients, with 159 patients receiving TIVA and 184 patients receiving DES. The only significant difference is extubation time, TIVA was faster than the DES group (8.5 ± 3.8 vs 9.4 ± 3.7 minutes; P = 0.04). The factors contributed to prolonged extubation were age, gender, body mass index, DES anesthesia, and anesthesia time.In our hospital, propofol-based TIVA by target-controlled infusion provides faster emergence compared with DES anesthesia; however, it did not improve OR efficiency in open major abdominal surgery. Older, male gender, higher body mass index, DES anesthesia, and lengthy anesthesia time were factors that contribute to extubation time.


Utilization of counseling and supportive services by female victims of domestic abuse.
Increasing attention to the high prevalence of domestic violence (DV) and its impact on women's physical and mental health has resulted in expanded services for abused women. Abused women appear to underutilize the formal counseling services available in many communities, however, and further research is needed to identify factors related to service utilization. In the present study, 1,746 women assaulted by a male intimate partner were identified from a larger pool of women interviewed by Pretrial Services following the arrest of their spouse/partner on domestic abuse charges. The women were selected for the current study if they reported prior physical assaults perpetrated by the same spouse/partner listed in the instant offense. In addition to describing previous physical assaults and psychological abuse by their current spouse/partner, women were also asked whether they had ever sought "formal counseling/supportive services" to address the abuse. Consistent with the prior literature, only a minority of the victims reported prior use of these services (14.9%). Additional analyses indicated that the likelihood of having accessed services varied as a function of victim demographic factors (race, relationship to the offender, income), characteristics of the prior DV (prior injury by partner, forced sexual activity, prior psychological abuse), and whether the victim's children witnessed the fighting. Limitations of the study and implications for service providers and the courts are discussed.