Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis.
The place of long-term psychodynamic psychotherapy (LTPP) within psychiatry is controversial. Convincing outcome research for LTPP has been lacking. To examine the effects of LTPP, especially in complex mental disorders, ie, patients with personality disorders, chronic mental disorders, multiple mental disorders, and complex depressive and anxiety disorders (ie, associated with chronic course and/or multiple mental disorders), by performing a meta-analysis. Studies of LTPP published between January 1, 1960, and May 31, 2008, were identified by a computerized search using MEDLINE, PsycINFO, and Current Contents, supplemented by contact with experts in the field. Only studies that used individual psychodynamic psychotherapy lasting for at least a year, or 50 sessions; had a prospective design; and reported reliable outcome measures were included. Randomized controlled trials (RCTs) and observational studies were considered. Twenty-three studies involving a total of 1053 patients were included (11 RCTs and 12 observational studies). Information on study characteristics and treatment outcome was extracted by 2 independent raters. Effect sizes were calculated for overall effectiveness, target problems, general psychiatric symptoms, personality functioning, and social functioning. To examine the stability of outcome, effect sizes were calculated separately for end-of-therapy and follow-up assessment. According to comparative analyses of controlled trials, LTPP showed significantly higher outcomes in overall effectiveness, target problems, and personality functioning than shorter forms of psychotherapy. With regard to overall effectiveness, a between-group effect size of 1.8 (95% confidence interval [CI], 0.7-3.4) indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96% of the patients in the comparison groups (P = .002). According to subgroup analyses, LTPP yielded significant, large, and stable within-group effect sizes across various and particularly complex mental disorders (range, 0.78-1.98). There is evidence that LTPP is an effective treatment for complex mental disorders. Further research should address the outcome of LTPP in specific mental disorders and should include cost-effectiveness analyses.


A preliminary report on the medical profile of disabled persons living in Zhabei District, Shanghai, Mainland China.
The prevalence of chronic diseases and their risk factors in different general populations are well documented, but little is known about disabled populations in China. The purpose of this study is to report available data on the medical profile of disabled persons living in Zhabei District, Shanghai, Mainland China. It also aimed to explore the association between any medical conditions, types and severity of disabilities and socio-demographic factors. Nine hundred and sixty-one disabled persons underwent physical medical examination to identify predisposing conditions for chronic diseases (hypertension and elevated glucose, lipids and triglyceride levels) and to diagnose two common chronic diseases - heart disease and diabetes. Logistic regression was used to assess the influence of age, gender, disability type, disability severity, education level, employment status, socio-economic status or marital status on chronic diseases and predisposing factors. The mean age of the participants was 53 (±12.5) years. The most prevalent types of disability were physical disability (44.9%), visual impairment (28.8%) and intellectual disability (12.5%). Hyperlipidemia was most prevalent (17.1%), followed by hypertension (15.3%), heart disease (7.2%) and diabetes (6.0%). These conditions were not associated with the type or the severity of disability in this sample. Males were more likely to have hypertension (OR=1.75; 95% CI: 1.05, 2.93) and elevated triglycerides (OR=1.84; 95% CI: 1.05, 3.20). The unemployed (OR=4.80, 95% CI: 1.45, 15.76) and older participants (OR=1.04, 95% CI: 1.02, 1.07) were more likely to have elevated blood glucose levels. Divorced individuals were more likely to be diagnosed with heart disease (OR=3.72; 95% CI: 1.37, 10.09) and those with better socio-economic backgrounds (OR=3.09; 95% CI: 1.05, 9.15) and the older disabled (OR=1.08, 95% CI: 1.04, 1.12) were more likely to have diabetes. This preliminary study found that abnormal clinical findings were not related to the type or the severity of disability. Most abnormal findings were, however, related to increasing age, consistent with previous findings in the general Chinese population.


Do burned-out and work-engaged employees differ in the functioning of the hypothalamic-pituitary-adrenal axis?
The central aim of the present study was to examine differences in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis between 29 burned-out, 33 work-engaged, and 26 healthy reference managers, as identified with the Maslach Burnout Inventory-General Survey and the Utrecht Work Engagement Scale. All of the managers were employed in a large Dutch telecommunications company. Salivary cortisol was sampled on three consecutive workdays and one nonworkday to determine the cortisol awakening response. Salivary dehydroepiandrosterone-sulfate (DHEAS), a cortisol counterbalancing product of the HPA axis, was measured on these days 1 hour after managers awakened. The dexamethasone suppression test was used to investigate the feedback sensitivity of the HPA axis. The morning cortisol levels were higher on the workdays than on the nonworkday, but this effect did not differ between the three groups. The burned-out, work-engaged, and reference groups did not differ in the cortisol and DHEAS levels, the slope of the cortisol awakening response, and the cortisol : DHEAS ratio. The work-engaged group showed a stronger cortisol suppression in response to the dexamethasone suppression test than the other two groups, the finding suggesting higher feedback sensitivity among work-engaged managers. Burned-out and work-engaged managers only differ marginally in HPA-axis functioning.


Validity of claims-based stroke algorithms in contemporary Medicare data: reasons for geographic and racial differences in stroke (REGARDS) study linked with medicare claims.
The accuracy of stroke diagnosis in administrative claims for a contemporary population of Medicare enrollees has not been studied. We assessed the validity of diagnostic coding algorithms for identifying stroke in the Medicare population by linking data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study to Medicare claims. The REGARDS Study enrolled 30 239 participants ≥45 years in the United States between 2003 and 2007. Stroke experts adjudicated suspected strokes, using retrieved medical records. We linked data for participants enrolled in fee-for-service Medicare to claims files from 2003 through 2009. Using adjudicated strokes as the gold standard, we calculated accuracy measures for algorithms to identify incident and recurrent strokes. We linked data for 15 089 participants, among whom 422 participants had adjudicated strokes during follow-up. An algorithm using primary discharge diagnosis codes for acute ischemic or hemorrhagic stroke (International Classification of Diseases, Ninth Revision, Clinical Modification codes: 430, 431, 433.x1, 434.x1, 436) had a positive predictive value of 92.6% (95% confidence interval, 88.8%-96.4%), a specificity of 99.8% (99.6%-99.9%), and a sensitivity of 59.5% (53.8%-65.1%). An algorithm using only acute ischemic stroke codes (433.x1, 434.x1, 436) had a positive predictive value of 91.1% (95% confidence interval, 86.6%-95.5%), a specificity of 99.8% (99.7%-99.9%), and a sensitivity of 58.6% (52.4%-64.7%). Claims-based algorithms to identify stroke in a contemporary Medicare cohort had high positive predictive value and specificity, supporting their use as outcomes for etiologic and comparative effectiveness studies in similar populations. These inpatient algorithms are unsuitable for estimating stroke incidence because of low sensitivity.


Directional selection can drive the evolution of modularity in complex traits.
Modularity is a central concept in modern biology, providing a powerful framework for the study of living organisms on many organizational levels. Two central and related questions can be posed in regard to modularity: How does modularity appear in the first place, and what forces are responsible for keeping and/or changing modular patterns? We approached these questions using a quantitative genetics simulation framework, building on previous results obtained with bivariate systems and extending them to multivariate systems. We developed an individual-based model capable of simulating many traits controlled by many loci with variable pleiotropic relations between them, expressed in populations subject to mutation, recombination, drift, and selection. We used this model to study the problem of the emergence of modularity, and hereby show that drift and stabilizing selection are inefficient at creating modular variational structures. We also demonstrate that directional selection can have marked effects on the modular structure between traits, actively promoting a restructuring of genetic variation in the selected population and potentially facilitating the response to selection. Furthermore, we give examples of complex covariation created by simple regimes of combined directional and stabilizing selection and show that stabilizing selection is important in the maintenance of established covariation patterns. Our results are in full agreement with previous results for two-trait systems and further extend them to include scenarios of greater complexity. Finally, we discuss the evolutionary consequences of modular patterns being molded by directional selection.


Genetic structure and signatures of selection in grey reef sharks (Carcharhinus amblyrhynchos).
With overfishing reducing the abundance of marine predators in multiple marine ecosystems, knowledge of genetic structure and local adaptation may provide valuable information to assist sustainable management. Despite recent technological advances, most studies on sharks have used small sets of neutral markers to describe their genetic structure. We used 5517 nuclear single-nucleotide polymorphisms (SNPs) and a mitochondrial DNA (mtDNA) gene to characterize patterns of genetic structure and detect signatures of selection in grey reef sharks (Carcharhinus amblyrhynchos). Using samples from Australia, Indonesia and oceanic reefs in the Indian Ocean, we established that large oceanic distances represent barriers to gene flow, whereas genetic differentiation on continental shelves follows an isolation by distance model. In Australia and Indonesia differentiation at nuclear SNPs was weak, with coral reefs acting as stepping stones maintaining connectivity across large distances. Differentiation of mtDNA was stronger, and more pronounced in females, suggesting sex-biased dispersal. Four independent tests identified a set of loci putatively under selection, indicating that grey reef sharks in eastern Australia are likely under different selective pressures to those in western Australia and Indonesia. Genetic distances averaged across all loci were uncorrelated with genetic distances calculated from outlier loci, supporting the conclusion that different processes underpin genetic divergence in these two data sets. This pattern of heterogeneous genomic differentiation, suggestive of local adaptation, has implications for the conservation of grey reef sharks; furthermore, it highlights that marine species showing little genetic differentiation at neutral loci may exhibit patterns of cryptic genetic structure driven by local selection.


Relationship between mental health, sleep status and screen time among university students during the COVID-19 pandemic: a cross-sectional study.
On 20 July 2021, after the outbreak of COVID-19 at Nanjing Lukou International Airport, several universities started closed management and online teaching. This had a large impact on students' daily life and study, which may lead to mental health problems. The purpose of this study is to study the effect of screen time on mental health status of university students and the possible mediating effect of sleep status. This was a cross-sectional study. A web-based questionnaire survey was employed that included demographic characteristics, sleep status and mental health status (depression, anxiety and loneliness). The Pittsburgh Sleep Quality Index scale was used to assess sleep status, while the Centre for Epidemiologic Studies Depression (CES-D) scale, Generalised Anxiety Disorder-7 (GAD-7) scale and Emotional versus Social Loneliness Scale (ESLS) were used to assess depression, anxiety and loneliness, respectively. Linear and logistic regression models were developed and adjusted for confounding factors, and finally the mediating effects were tested using the Karlson-Holm-Breen method. Finally, 1070 valid questionnaires were included. Among these, 604 (56.45%) indicated depressive symptoms (CES-D score ≥16) and 902 (84.30%) indicated anxiety symptoms (GAD-7 score ≥10). The mean ESLS score (for loneliness) was 26.51±6.64. The relationship between screen time and depressive symptoms (OR 1.118, 95% CI 1.072 to 1.166) and anxiety symptoms (OR 1.079, 95% CI 1.023 to 1.138) remained significant after adjusting for confounding factors. Meanwhile, sleep status plays an intermediary role in screen time and mental health status (depression and anxiety) and accounts for 13.73% and 19.68% of the total effects, respectively. We did not find a significant association between screen time and loneliness. During the outbreak of COVID-19, screen time is inevitably prolonged among university students. There is a relationship between mental health and screen time, and sleep status plays a mediating role.


Maternal-neonatal listeriosis.
Listeriosis is a rare and severe foodborne infection caused by Listeria monocytogenes. It manifests as septicemia, neurolisteriosis, and maternal-fetal infection. In pregnancy, it may cause maternal fever, premature delivery, fetal loss, neonatal systemic and central nervous system infections. Maternal listeriosis is mostly reported during the 2nd and 3rd trimester of pregnancy, as sporadic cases or in the context of outbreaks. Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections. Here we review the clinical, pathophysiological, and microbiological features of maternal-neonatal listeriosis.


Quantitation of ICAM-1 expression in mouse lung during pneumonia.
In the systemic circulation, neutrophil emigration into sites of acute inflammation is mediated through the leukocyte adhesion complex, CD11/CD18. ICAM-1 is an inducible endothelial ligand for CD11a/CD18 and CD11b/CD18. Streptococcus pneumoniae elicits neutrophil emigration through a CD18-independent mechanism whereas Escherichia coli endotoxin elicits emigration through a CD18-dependent mechanism in rabbit lungs. To determine whether ICAM-1 is up-modulated in the lung during CD18-independent and CD18-dependent emigration, ultrastructural immunogold-labeling studies were performed on BALB/c mice given airway instillates of S. pneumoniae or E. coli endotoxin. Ultrathin cryosections of frozen lung tissue were immunogold labeled with the mAb YN1/1.7.4 against the murine homologue of human ICAM-1. Gold particles on the plasma membranes of alveolar endothelial and epithelial cells were quantitated by transmission electron microscopy. Capillary endothelial ICAM-1 expression did not change during neutrophil emigration toward S. pneumoniae, a CD18-independent pathway in rabbits. In contrast, ICAM-1 expression increased 4.2-fold in response to E. coli endotoxin (known to elicit CD18-dependent emigration in mice), suggesting that the mechanism of adhesion may be regulated by the expression of endothelial rather than neutrophil adhesion molecules. Constitutive expression of ICAM-1 on alveolar epithelial cells was 22-fold greater than on capillary endothelium. Epithelial expression was mainly restricted to type I pneumocytes, whereas type II pneumocytes, the precursors of type I cells, expressed little or no ICAM-1. However, during pneumonia, type II but not type I pneumocytes showed increased ICAM-1 expression, suggesting that ICAM-1 expression represents an early differentiation even in response to epithelial injury.


HGF, sIL-6R and TGF-β1 Play a Significant Role in the Progression of Multiple Myeloma.
Background. In the last few years, it has been widely reported that proinflammatory and angiogenic cytokines are important for the development and progression of multiple myeloma (MM). Objectives. To further validate and acquire more insight into this view we decided to check whether plasma levels of certain cytokines and their soluble receptors differ between MM patients and healthy subjects. Patients and Methods. The study was conducted in 76 MM patients aged 22 to 77 years (60±10 years) and 35 healthy controls aged 20 to 63 years (33±10 years). Plasma levels of interleukin-6 (IL-6), b-fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1), as well as soluble receptors for IL-6 (sIL-6R) and VEGF (sVEGF-R2) were measured using enzyme-linked immunosorbent assay (ELISA). Results. Significantly higher plasma levels of IL-6 (13.65±42.61 vs. 1.04±1.12 pg/ml, p=0.006), HGF (2174±2714 vs. 648±130 pg/ml, p<0.001), b-FGF (7.92±10.78 vs. 2.54±5.38 pg/ml, p<0.001) and sIL-6R (37.1±14.2 vs. 25.3±6.4 ng/ml, p=0.003) were observed in MM patients vs. healthy controls, respectively. Plasma sVEGF-R2 was significantly lower in MM patients than in controls (7518±2119 vs. 8725±1281 pg/ml, respectively; p<0.001). We observed an inverse correlation between length of treatment and the level of sIL-6R, and TGF-β1 in plasma. Conclusions. Plasma levels of HGF, b-FGF, IL-6 and sIL-6R in MM patients were higher when compared to the control group. Antineoplastic therapy leads to a time-dependent decrease in plasma levels of sIL-6R, and TGF-β1 in MM patients. Blood plasma level of HGF is an optimal measure to differentiate patients in whom disease is progressing versus patients who respond to therapy.


The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts.
Protein-RNA interactions are fundamental to core biological processes, such as mRNA splicing, localization, degradation, and translation. We developed a photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach to identify the mRNA-bound proteome using quantitative proteomics and to display the protein occupancy on mRNA transcripts by next-generation sequencing. Application to a human embryonic kidney cell line identified close to 800 proteins. To our knowledge, nearly one-third were not previously annotated as RNA binding, and about 15% were not predictable by computational methods to interact with RNA. Protein occupancy profiling provides a transcriptome-wide catalog of potential cis-regulatory regions on mammalian mRNAs and showed that large stretches in 3' UTRs can be contacted by the mRNA-bound proteome, with numerous putative binding sites in regions harboring disease-associated nucleotide polymorphisms. Our observations indicate the presence of a large number of mRNA binders with diverse molecular functions participating in combinatorial posttranscriptional gene-expression networks.


The Role of Tourism and Recreation in the Spread of Non-Native Species: A Systematic Review and Meta-Analysis.
Managing the pathways by which non-native species are introduced and spread is considered the most effective way of preventing species invasions. Tourism and outdoor recreation involve the frequent congregation of people, vehicles and vessels from geographically diverse areas. They are therefore perceived to be major pathways for the movement of non-native species, and ones that will become increasingly important with the continued growth of these sectors. However, a global assessment of the relationship between tourism activities and the introduction of non-native species-particularly in freshwater and marine environments-is lacking. We conducted a systematic review and meta-analysis to determine the impact of tourism and outdoor recreation on non-native species in terrestrial, marine and freshwater environments. Our results provide quantitative evidence that the abundance and richness of non-native species are significantly higher in sites where tourist activities take place than in control sites. The pattern was consistent across terrestrial, freshwater and marine environments; across a variety of vectors (e.g. horses, hikers, yachts); and across a range of taxonomic groups. These results highlight the need for widespread biosecurity interventions to prevent the inadvertent introduction of invasive non-native species (INNS) as the tourism and outdoor recreation sectors grow.


Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis.
To compare the efficacy and tolerability of paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology. Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions-Severity (CGI-S) score as factors. The dosage range of paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates ≥ 5% and with a ≥ 2% difference between paliperidone ER and risperidone were identified. Completion rates for placebo-treated subjects in paliperidone ER trials (n = 95) and risperidone trials (n = 122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p = 0.768). Completion rates for subjects receiving paliperidone ER 6-12 mg/day (n = 179), risperidone 2-4 mg/day (n = 113) or risperidone 4-6 mg/day (n = 129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: paliperidone ER vs risperidone 2-4 mg/day, p = 0.005; paliperidone ER vs risperidone 4-6 mg/day, p = 0.159). PANSS total score improvement with paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p < 0.05) and similar to risperidone 4-6 mg/day (0.2; p = 0.927). Placebo-adjusted AEs more common with paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with paliperidone ER and risperidone were similar (paliperidone ER vs risperidone 2-4 mg/day, p = 0.489; paliperidone ER vs risperidone 4-6 mg/day, p = 0.236). This indirect database analysis suggested that paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.


Glioblastomas with oligodendroglial component-common origin of the different histological parts and genetic subclassification.
Glioblastomas are the most common and most malignant brain tumors in adults. A small subgroup of glioblastomas contains areas with histological features of oligodendroglial differentiation (GBMO). Our objective was to genetically characterize the oligodendroglial and the astrocytic parts of GBMOs and correlate morphologic and genetic features with clinical data. The oligodendroglial and the "classic" glioblastoma parts of 13 GBMO were analyzed separately by interphase fluoreszence in situ hybridization (FISH) on paraffin sections using a custom probe set (regions 1p, 1q, 7q, 10q, 17p, 19q, cen18, 21q) and by comparative genomic hybridization (CGH) of microdissected paraffin embedded tumor tissue. We identified four distinct genetic subtypes in 13 GBMOs: an "astrocytic" subtype (9/13) characterized by +7/-10; an "oligodendroglial" subtype with -1p/-19q (1/13); an "intermediate" subtype showing +7/-1p (1/13), and an "other" subtype having none of the former aberrations typical for gliomas (2/13). The different histological tumor parts of GBMO revealed common genetic changes in all tumors and showed additional aberrations specific for each part. Our findings demonstrate the monoclonal origin of GBMO followed by the development of the astrocytic and oligodendroglial components. The diagnostic determination of the genetic signatures may allow for a better prognostication of the patients.


Photoinduced ultrafast charge separation in colloidal 2-dimensional CdSe/CdS-Au hybrid nanoplatelets and corresponding application in photocatalysis.
Multicomponent hybrid nanocrystals (HNC) consisting of a semiconductor and metallic domains are an important class of nanostructured materials demonstrating useful applications and interesting basic knowledge. In this scenario, Au nanoparticle (NP) islands of ∼2 nm have been grown on unique two dimensional (2D) CdSe/CdS core@shell hexagonal nanoheteroplatelets of 20 nm diameter to form unprecedented 2D CdSe/CdS-Au HNCs and detailed optical characterization has been carried out to determine the dimensionality based electron transfer dynamics on the ultrafast scale. Steady state optical absorption studies show that upon growing Au NPs onto the 2D nanoplates, a new band appears in the red region of the spectra (500-800 nm), which suggests a strong interaction between the exciton of the core-shell and the plasmon of the metal NPs. Fluorescence studies showed the quenching of emission of the semiconductor domains upon the growth of the metallic domains. Detailed optical and TRPL studies suggested efficient charge transfer from the 2D CdSe/CdS to the Au domains, irrespective of excitation wavelength. Femtosecond transient absorption studies suggest that the electron transfer from the 2D hybrid nanocrystals to the metal domain is on an ultrafast time scale (∼800 fs). No evidence is observed for charge transfer from the 2 nm Au domains to the semiconductor seeds. The broad absorption in the visible region of the hybrid nanocrystals and the ultrafast charge transfer facilitates very efficient photo-catalytic reactions under direct sun light, as a case study.


Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.
Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings.


Nonendoscopic, minimally invasive calvarial vault remodeling without postoperative helmeting for sagittal synostosis.
Multiple surgical procedures have been described for the management of isolated nonsyndromic sagittal synostosis. Minimally invasive techniques have been recently emphasized, but these techniques necessitate the use of an endoscope and postoperative helmeting. The authors assert that a safe and effective, more "minimalistic" approach is possible, avoiding the use of endoscopic visualization and routine postoperative application of a cranial orthosis. A single-institution cohort analysis was performed on 18 cases involving infants treated for isolated nonsyndromic sagittal synostosis between 2008 and 2010 using a nonendoscopic, minimally invasive calvarial vault remodeling (CVR) procedure without postoperative helmeting. The surgical technique is described. Variables analyzed were: age at time of surgery, sex, estimated blood loss (EBL), operative time, intraoperative complications, postoperative complications, length of stay, pre- and postoperative cephalic index (CI), clinical impressions, and results of a 5-question nonstandardized questionnaire administered to patient caregivers regarding outcome. Eleven male and 7 female infants (mean age 2.3 months) were included in the study. The mean duration of follow-up was 16.4 months (range 6-38 months). The mean procedural time was 111 minutes (range 44-161 minutes). The mean length of stay was 2.3 days (range 2-3 days). The mean EBL in all 18 patients was 101.4 ml (range 30-475 ml). One patient had significant bone bleeding resulting in an EBL of 475 ml. Excluding this patient, the mean EBL was 79.4 ml (range 30-150 ml). There were no deaths or intraoperative complications; one patient had a superficial wound infection. The mean CI was 69 preoperatively versus 79 postoperatively, a statistically significant difference (p < 0.0001). Two patients were offered helmeting for suboptimal surgical outcome; one family declined and the single helmeted patient showed improvement at 2 months. No patient has undergone further surgery for correction of primary deformity, secondary deformities, or bony irregularities. Complete questionnaire data were available for 14 (78%) of the 18 patients; 86% of the respondents were pleased with the cosmetic outcome, 92% were happy to have avoided helmeting, 72% were doubtful that helmeting would have provided more significant correction, and 86% were doubtful that further surgery would be necessary. Small, palpable, aesthetically insignificant skull irregularities were reported by family members in 6 cases (43%). The authors present a nonendoscopic, minimally invasive CVR procedure without postoperative helmeting. Their small series demonstrates this to be a safe and efficacious procedure for isolated nonsyndromic sagittal synostosis, with improvements in CI at a mean follow-up of 16.1 months, commensurate with other techniques, and with overall high family satisfaction. Use of a CVR cranial orthosis in a delayed fashion can be effective for the infrequent patient in whom this approach results in suboptimal correction.


Sources of exposure to and public health implications of organophosphate pesticides.
To review the public health significance of organophosphate pesticide exposure in the United States of America. Since the situation of high organophosphate pesticide exposure and the concomitant health risks in the developing countries of the world is well known, this article seeks to highlight the public health significance of organophosphate exposure in the United States, where it is less common than in many other nations. Looking at the situation in the United States would serve to further emphasize the seriousness of organophosphate pesticide-related health issues in developing countries. A search for journal articles on organophosphate pesticides and organophosphate exposure was done on the PubMed electronic bibliographic database system of the National Library of Medicine of the United States. To supplement that search, information on organophosphate toxicity, biological monitoring, and regulation of pesticides was obtained from other published articles, textbooks, and relevant Internet sites. Organophosphate pesticides are a group of chemicals that are mainly used in agriculture. Organophosphates inhibit the activity of both the cholinesterase (ChE) enzymes-red blood cell (RBC) ChE and serum ChE-resulting in the cholinergic features of organophosphate toxicity. A 50% reduction in serum ChE activity from the baseline is an indication of acute organophosphate toxicity. The RBC ChE activity, which is less rapidly depressed than the serum ChE activity, is a measure of chronic exposure to organophosphates. Exposures to organophosphates are broadly classified into two categories: occupational and environmental. Occupational exposures occur among agricultural workers (including migrant farmworkers), industrial workers, pest control exterminators, and other workers. Nonoccupational exposure affects a large segment of the general population in the United States. Residential exposures come from organophosphate pesticide use by exterminators and by household residents as well as from dietary and accidental exposures. Other environmental exposures occur in public places and areas close to farms, and exposures could also happen from organophosphate use in chemical warfare or terrorism. In the United States some organophosphate pesticides are restricted by the Environmental Protection Agency in order to protect humans, animals, and the environment. In addition, the Food Quality Protection Act regulates dietary exposure to pesticides, particularly for infants and children. Organophosphate pesticides continue to pose a risk to human health in the United States. Biological monitoring should be used to strictly regulate occupational exposures to organophosphates and thus protect the health and safety of workers. Among the public there should be an increased awareness of environmental exposure to organophosphates as well as of the threat of chemical warfare or terrorism.


125I-thrombin binds to clustered receptors on noncoated regions of mouse embryo cell surfaces.
We used electron microscope autoradiography (EMAR) to visualize the interaction of 125I-thrombin with its surface receptors on mouse embryo (ME) cells. Autoradiographic grains were spaced over the surface of cells in a periodic nonrandom pattern, indicating 125I-thrombin association with clusters of thrombin receptors. The grain spacing varied slightly from cell to cell, indicating subpopulations of cells with different numbers of thrombin receptors. The average distance between grains on ME cells after binding 125I-thrombin (125 ng/ml) at 37 degrees C was 1.65 +/- 0.49 microns. The average distance between grains on prefixed cells and cells incubated with 125I-thrombin at 4 degrees C was not significantly different from that observed at 37 degrees C. This indicates that thrombin receptors are clustered before thrombin binding and that the thrombin receptor aggregates do not redistribute into large aggregates on the surface of cells subsequent to thrombin binding. The number of grains per cluster also does not change under these three binding conditions. Thus, the number of occupied receptors in each cluster appears to be constant. On the basis of the average grain number and spacing, we estimate that each cluster is approximately 400 nm in diameter containing approximately 550 thrombin-binding sites. These receptor-clusters are not associated with specialized structures or coated regions of the membrane. Additionally, grains observed within cells were not found associated with coated vesicles. Therefore, neither the clustering patterns nor internalization of 125I-thrombin are characteristic of molecules which bind to receptors and are internalized by receptor-mediated endocytosis.


Developing locally relevant outreach programs for same sex attracted youth in regional areas.
This paper reports on the process evaluation of the Same Sky project,1 which was aimed at developing regional community support programs for same sex attracted youth (SSAY) and their families in four regional sites in Western Australia. A multi-faceted approach modelled on successful urban outreach programs was used to build professional capacity and develop peer-based support programs in the community. A triangulated mixed methods evaluation design was implemented to capture various outputs and outcomes of the intervention strategies. Data were collected via interviews and questionnaires and by assessing community readiness through community participation and involvement in the programs and through demand for printed resources. There was increased community awareness of same sex attraction issues and professional capacity to help SSAY regionally following training and distribution of printed resources. Improved alliances between regional and metropolitan service providers were also evident. Not all of the planned peer support interventions could be implemented. Drop-in centres and peer support groups proved particularly problematic to establish. Basing the project officer in one of the rural sites was notable in improving project progress. Some aspects of the urban outreach models for SSAY were transportable to rural areas, others were not. Some specific problems identified were a lack of community readiness, a distrust of 'outsiders' to the community, significant differences between the needs of SSAY across regional demonstration sites, and difficulties in engaging locally based volunteers and agencies to develop and run rural outreach services.


Sacroiliac Joint Fusion Methodology - Minimally Invasive Compared to Screw-Type Surgeries: A Systematic Review and Meta-Analysis.
Sacroiliac (SI) joint fusion represents a unique area of orthopedic surgery with procedural literature dating to the early 1920s, showing limited innovation in either technique or hardware over the last 90 years. Recent improvements in the diagnosis and treatment of SI joint dysfunction warrant comparisons to older surgical techniques. To evaluate treatment efficacies and patient outcomes associated with minimally invasive joint fusion in comparison to screw-type surgeries. Systematic review and meta-analysis. Electronic databases, EMBASE, Pubmed (Medline), manual bibliography cross-referencing for published works until Dec. 31, 2017. A thorough literature search was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Data repositories accessed included Pubmed and EMBASE, until Dec. 31, 2017. All studies evaluating sacroiliac joint fusion and reporting quantifiable outcome data were included. Exclusion criteria included nonhuman studies, qualitative reviews, and meta-analyses. Data compilation, coding, and extraction were performed using MedAware Systems proprietary software. Data from each study were extracted by 2 analysts, using software that allowed automatic comparisons of all data fields. The standardized mean difference (SMD) was used as a summary statistic for pooling outcomes data across studies. Multiple outcome measures were grouped into 3 categories, according to similarity of measurements - Pain, Disability/Physical Function, and Global/QOL. A total of 20 studies had adequate data to calculate a SMD, and were included in the meta-analysis. Results of iFuse trials were compared to screw type trials, pooled in 3 categories of outcomes - Pain, Disability/Physical Function, and Global/QOL. The Pain category showed a statistically significant (P = 0.03) difference in outcomes for patients receiving the iFuse implant compared to screw types (SMD = 2.04 [95%CI: 1.76 to 2.33] vs. 1.28 [95%CI: 0.47 to 2.09]), with iFuse showing significantly better outcomes. The Disability category also showed a statistically significant (P = 0.01) difference in outcomes for patients receiving the iFuse implant compared to screw types (SMD = 1.68 [95%CI: 1.43 to 1.94] vs. 0.26 [95%CI: -1.90 to 2.41]), with iFuse showing significantly better outcomes. For Global/Quality of Life (QOL) outcomes, there was a significant difference (P = 0.04) between iFuse and screw-type procedures (SMD = 0.99 [95%CI: 0.75 to 1.24] vs. 0.60 [95%CI: 0.33 to 0.88]), with iFuse showing significantly better outcomes. There was a statistically significant correlation between lower baseline Oswestry Disability Index (ODI) and Short Form 36 Health Survey (SF-36) values and better post treatment outcomes (r2 = 0.47, P < 0.01, and r2 = 0.30, P < 0.01, respectively). An association was found between pain at baseline and better outcomes (r2 = 0.21, P < 0.01), where worse baseline pain was associated with better outcomes. There was a limited number of studies in this meta-analysis with treatments that could be properly classified as screw-type. In this analysis, compared to screw-type surgeries, the iFuse system showed statistically superior outcomes. This was the case when outcome measures were classified into 3 main categories - Pain, Disability/Physical Function, and Global/QOL. Meta-analysis, systematic review, sacroiliac joint, sacroiliac joint fusion.


Learning through reflection in the community: the relevance of Schon's theories of coaching to nursing education.
In 1992, as part of a study funded by the English National Board for Nursing, Midwifery and Health Visiting, the author conducted 26 interviews, 12 with students on the newly-introduced Diploma in Higher Education for Nurses, and 14 with District Nursing Sisters who supervised them during their community placements. The approach to the work was interpretive and was guided by phenomenology. It was discovered that one of the most valuable contributions of their 'community experience' was the opportunities it gave the students to 'think through' and develop their own ideas about their practice. The author's interpretation of these findings was influenced by Donald Schon's ideas about reflective practice and coaching. His theory that professional practice is based on 'knowing-in-action' and 'theories-in-use' which are formulated and modified through a process of 'reflection-in-action' seemed to have direct relevance for the learning acquired by students. The help and guidance given to students by their supervisors bore some resemblance to the types of coaching advocated by Schon, to which he gave the names 'Joint Experimentation', 'Follow Me' and 'Hall of Mirrors'. The interpretation placed on the data discussed here also, however, differs from Schon's theories in advocating that more attention should be given to the academic theory referred to by him as 'technical rationality'.


Visual coding with a population of direction-selective neurons.
The brain decodes the visual scene from the action potentials of ∼20 retinal ganglion cell types. Among the retinal ganglion cells, direction-selective ganglion cells (DSGCs) encode motion direction. Several studies have focused on the encoding or decoding of motion direction by recording multiunit activity, mainly in the visual cortex. In this study, we simultaneously recorded from all four types of ON-OFF DSGCs of the rabbit retina using a microelectronics-based high-density microelectrode array (HDMEA) and decoded their concerted activity using probabilistic and linear decoders. Furthermore, we investigated how the modification of stimulus parameters (velocity, size, angle of moving object) and the use of different tuning curve fits influenced decoding precision. Finally, we simulated ON-OFF DSGC activity, based on real data, in order to understand how tuning curve widths and the angular distribution of the cells' preferred directions influence decoding performance. We found that probabilistic decoding strategies outperformed, on average, linear methods and that decoding precision was robust to changes in stimulus parameters such as velocity. The removal of noise correlations among cells, by random shuffling trials, caused a drop in decoding precision. Moreover, we found that tuning curves are broad in order to minimize large errors at the expense of a higher average error, and that the retinal direction-selective system would not substantially benefit, on average, from having more than four types of ON-OFF DSGCs or from a perfect alignment of the cells' preferred directions.


Late diagnosis of abdominal aortic aneurysms substantiates underutilization of abdominal aortic aneurysm screening for Medicare beneficiaries.
Abdominal aortic aneurysm (AAA) screening remains largely underutilized in the U.S., and it is likely that the proportion of patients with aneurysms requiring prompt treatment is much higher compared with well-screened populations. The goals of this study were to determine the proportion of AAAs that required prompt repair after diagnostic abdominal imaging for U.S. Medicare beneficiaries and to identify patient and hospital factors contributing to early vs late diagnosis of AAA. Data were extracted from Medicare claims records for patients at least 65 years old with complete coverage for 2 years who underwent intact AAA repair from 2006 to 2009. Preoperative ultrasound and computed tomography was tabulated from 2002 to repair. We defined early diagnosis of AAA as a patient with a time interval of greater than 6 months between the first imaging examination and the index procedure, and late diagnosis as patients who underwent the index procedure within 6 months of the first imaging examination. Of 17,626 patients who underwent AAA repair, 14,948 met inclusion criteria. Mean age was 77.5 ± 6.1 years. Early diagnosis was identified for 60.6% of patients receiving AAA repair, whereas 39.4% were repaired after a late diagnosis. Early diagnosis rates increased from 2006 to 2009 (59.8% to 63.4%; P < .0001) and were more common for intact repair compared with repair after rupture (62.9% vs 35.1%; P < .0001) and for women compared with men (66.3% vs 59.0%; P < .0001). On multivariate analysis, repair of intact vs ruptured AAAs (odds ratio, 3.1; 95% confidence interval, 2.7-3.6) and female sex (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) remained the strongest predictors of surveillance. Although intact repairs were more likely to be diagnosed early, over one-third of patients undergoing repair for ruptured AAAs received diagnostic abdominal imaging greater than 6 months prior to surgery. Despite advances in screening practices, significant missed opportunities remain in the U.S. Medicare population for improving AAA care. It remains common for AAAs to be diagnosed when they are already at risk for rupture. In addition, a significant proportion of patients with early imaging rupture prior to repair. Our findings suggest that improved mechanisms for observational management are needed to ensure optimal preoperative care for patients with AAAs.


National water, food, and trade modeling framework: The case of Egypt.
This paper introduces a modeling framework for the analysis of real and virtual water flows at national scale. The framework has two components: (1) a national water model that simulates agricultural, industrial and municipal water uses, and available water and land resources; and (2) an international virtual water trade model that captures national virtual water exports and imports related to trade in crops and animal products. This National Water, Food & Trade (NWFT) modeling framework is applied to Egypt, a water-poor country and the world's largest importer of wheat. Egypt's food and water gaps and the country's food (virtual water) imports are estimated over a baseline period (1986-2013) and projected up to 2050 based on four scenarios. Egypt's food and water gaps are growing rapidly as a result of steep population growth and limited water resources. The NWFT modeling framework shows the nexus of the population dynamics, water uses for different sectors, and their compounding effects on Egypt's food gap and water self-sufficiency. The sensitivity analysis reveals that for solving Egypt's water and food problem non-water-based solutions like educational, health, and awareness programs aimed at lowering population growth will be an essential addition to the traditional water resources development solution. Both the national and the global models project similar trends of Egypt's food gap. The NWFT modeling framework can be easily adapted to other nations and regions.


Gamma knife radiosurgery for cerebellopontine angle meningiomas: a multicenter study.
Resection of cerebellopontine angle (CPA) meningiomas may result in significant neurological morbidity. Radiosurgery offers a minimally invasive alternative to surgery. To evaluate, in a multicenter cohort study, the outcomes of patients harboring CPA meningiomas who underwent Gamma Knife radiosurgery (GKRS). From 7 institutions participating in the North American Gamma Knife Consortium, 177 patients with benign CPA meningiomas treated with GKRS and at least 6 months radiologic follow-up were included for analysis. The mean age was 59 years and 84% were female. Dizziness or imbalance (48%) and cranial nerve (CN) VIII dysfunction (45%) were the most common presenting symptoms. The median tumor volume and prescription dose were 3.6 cc and 13 Gy, respectively. The mean radiologic and clinical follow-up durations were 47 and 46 months, respectively. Multivariate regression analyses were performed to identify the predictors of tumor progression and neurological deterioration. The actuarial rates of progression-free survival at 5 and 10 years were 93% and 77%, respectively. Male sex (P = .014), prior fractionated radiation therapy (P = .010), and ataxia at presentation (P = .002) were independent predictors of tumor progression. Symptomatic adverse radiation effects and permanent neurological deterioration were observed in 1.1% and 9% of patients, respectively. Facial spasms at presentation (P = .007) and lower maximal dose (P = .011) were independently associated with neurological deterioration. GKRS is an effective therapy for CPA meningiomas. Depending on the patient and tumor characteristics, radiosurgery can be an adjuvant treatment to initial surgical resection or a standalone procedure that obviates the need for resection in most patients.


Practical Considerations for Using Online Methods to Engage Patients in Guideline Development.
Clinical practice guidelines (CPGs) have been widely used in healthcare policy, practice, and for suggesting future research. As patients increasingly become involved in CPG development to produce patient-centered recommendations, more research is needed on methods to engage patients, particularly methods allowing for scalable engagement of large, diverse, and geographically distributed groups of patients. In this article, we discuss practical considerations for using online methods to engage patients in CPG development. To inform this discussion, we conducted a rapid, systematic review of literature on patient involvement in CPG development and used qualitative evidence synthesis techniques to make inferences about potential advantages and challenges of using online methods to engage patients in this context. We identified 79 articles containing information about involving patients in CPG development. Potential advantages include the ability of online methods to facilitate greater openness and honesty by patients, as well as to reflect the diversity of patient views, which in turn further improve the utility of CPGs. Potential challenges of using online methods may include the extra skill, time, and certain types of resources that may be needed for patient engagement, as well as the difficulty engaging specific patient populations. However, these challenges are mitigated by growing calls for patient engagement as normative for CPG development in addition to patients' increasing familiarity with online technologies. These practical considerations should be examined empirically as guideline development groups further explore the appropriateness of using online methods to engage patients across different stages of CPG development.


An evaluation of the protective role of α-tocopherol on free radical induced hepatotoxicity and nephrotoxicity due to chromium in rats.
To avert the health problems induced by many environmental pollutants, available antioxidants have been evaluated. The present study was aimed to investigate whether α-tocopherol could protect the hexavalent chromium (Cr VI)-induced peroxidation in the liver and kidney and to explore the underlying mechanism of the same. A total of 24 Wistar adult female rats were equally divided into four groups. Group 1 served as control while Groups 2 and 3 were administered K2Cr2O7(10 mg/kg b.wt. s.c. single dose). In addition to (Cr VI), Group 3 also received α-tocopherol (125 mg/kg, daily) by oral gavage for 14 days. Group 4 was maintained as α-tocopherol control (dose as above). At the end of 14 days, blood samples were drawn for hematology. Subsequently, all the rats were sacrificed to collect liver and kidney samples for assay of tissue peroxidation markers, antioxidant markers and functional markers and histopathology. Administration of chromium (Cr VI) in Group 2 significantly (P < 0.05) reduced the antioxidant markers such as superoxide dismutase and reduced glutathione along with significant (P < 0.05) increase in peroxidation markers such as malondialdehyde and protein carbonyls in the liver and kidney as compared with other groups. The functional markers in serum such as total protein was decreased significantly (P < 0.05), whereas other functional markers viz. alanine transaminase, blood urea nitrogen and creatinine were increased significantly (P < 0.05) in Group 2 as compared with the other groups. Significant (P < 0.05) decrease in hemoglobin, packed cell volume, total erythrocyte count, mean corpuscular volume, mean corpuscular hemoglobin and total leukocyte count were observed in Cr VI treated Group 2 rats. Prominent pathological changes were observed in the liver and kidney of Group 2. Co-treatment with α-tocopherol in Group 3 rats significantly (P < 0.05) reversed the Cr VI induced changes. The parameters in the study in Group 4 did not differ as compared with Group 1. α-tocopherol exhibited protective effect against Cr VI-induced damage to the liver and kidney by inhibition of lipid peroxidation owing its antioxidant activity.


Bottlenecks and roadblocks in high-throughput XAS for structural genomics.
Structural and functional characterization of the entire protein complement (the proteome) of an organism can provide an infrastructure upon which questions about biological pathways and systems biology can be framed. The technology necessary to perform this proteome-level structural and functional characterization is under development in numerous structural genomics and functional genomics initiatives. Given the ubiquity of metal active sites in a proteome, it seems appropriate to ask whether comprehensive local structural characterization of metal sites within a proteome (metalloproteomics) is either a valid or obtainable goal. With a proteome-wide knowledge of the active-site structures of all metalloproteins, one could start to ask how metal insertion, cluster assembly and metalloprotein expression are affected by growth conditions or developmental status etc. High-throughput X-ray absorption spectroscopy (HTXAS) is being developed as a technology for investigating the metalloproteome. In creating a pipeline from genome to metalloproteome, several bottlenecks to high-throughput determination of metal-site structures must be overcome. For example, automation of arraying small samples for XAS examination must be invented, automation of rapid data collection of multiple low-volume low-concentration samples must be developed, automation of data reduction and analysis must be perfected. Discussed here are the promises and the pitfalls of HTXAS development, including the results of initial feasibility experiments.


Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial.
Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0·83, 95% CI 0·63-1·09; p=0·18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1·91, 1·06-3·44; p=0·0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0·82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0·41) and sepsis (seven [1%] vs six [1%]; p=0·79). In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians' Services Incorporated.


Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma.
Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy. EGFR mutations in exon19 and exon21 named drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex, and smoking status showed that drug-sensitive EGFR mutations were significantly related to longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P < 0.001). In addition, we investigated the impact of sex and smoking status according to EGFR mutation status, and the impact of EGFR mutation status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with longer OS and PFS according to EGFR mutation status. Drug-sensitive EGFR mutations were significantly associated with longer OS and PFS according to sex or smoking status. Our results indicated that drug-sensitive EGFR mutations were the only independent factor for longer survival of patients treated with gefitinib, suggesting that patient selection based on EGFR mutation status for gefitinib therapy will lead to a better outcome for patients with lung adenocarcinoma.


Efficacy of low power laser therapy in fibromyalgia: a single-blind, placebo-controlled trial.
Low energy lasers are widely used to treat a variety of musculoskeletal conditions including fibromyalgia, despite the lack of scientific evidence to support its efficacy. A randomised, single-blind, placebo-controlled study was conducted to evaluate the efficacy of low-energy laser therapy in 40 female patients with fibromyalgia. Patients with fibromyalgia were randomly allocated to active (Ga-As) laser or placebo laser treatment daily for two weeks except weekends. Both the laser and placebo laser groups were evaluated for the improvement in pain, number of tender points, skinfold tenderness, stiffness, sleep disturbance, fatigue, and muscular spasm. In both groups, significant improvements were achieved in all parameters (p<0.05) except sleep disturbance, fatigue and skinfold tenderness in the placebo laser group (p>0.05). It was found that there was no significant difference between the two groups with respect to all parameters before therapy whereas a significant difference was observed in parameters as pain, muscle spasm, morning stiffness and tender point numbers in favour of laser group after therapy (p<0.05). None of the participants reported any side effects. Our study suggests that laser therapy is effective on pain, muscle spasm, morning stiffness, and total tender point number in fibromyalgia and suggests that this therapy method is a safe and effective way of treatment in the cases with fibromyalgia.


A urinary extracellular vesicle microRNA biomarker discovery pipeline; from automated extracellular vesicle enrichment by acoustic trapping to microRNA sequencing.
Development of a robust automated platform for enrichment of extracellular vesicles from low sample volume that matches the needs for next-generation sequencing could remove major hurdles for genomic biomarker discovery. Here, we document a protocol for urinary EVs enrichment by utilizing an automated microfluidic system, termed acoustic trap, followed by next-generation sequencing of microRNAs (miRNAs) for biomarker discovery. Specifically, we compared the sequencing output from two small RNA library preparations, NEXTFlex and CATS, using only 130 pg of input total RNA. The samples prepared using NEXTflex was found to contain larger number of unique miRNAs that was the predominant RNA species whereas rRNA was the dominant RNA species in CATS prepared samples. A strong correlation was found between the miRNA expressions of the acoustic trap technical replicate in the NEXTFlex prepared samples, as well as between the acoustic trap and ultracentrifugation enrichment methods. Together, these results demonstrate a robust and automated strategy for biomarker discovery from small volumes of urine.


[HIV-related lymphoma in a public hospital in Chile. Analysis of 55 cases].
Cancer is the third cause of death in patients infected with human immunodeficiency virus (HIV) and lymphoma is the most common type. To describe the clinical characteristics, histology, risk factors and prognosis of these patients, in a Chilean public hospital in Chile. Records of 55 patients (45 males) aged between 23 and 67 years with lymphoma and HIV positive serology, diagnosed between 1992-2008, were reviewed. Six patients (11%) had Hodgkin lymphoma (HL) and the rest, non-Hodgkin lymphoma (NHL). B-cell phenotype constituted 83.7% of NHL cases. The most common subtypes of all the lymphoma were diffuse large B cell lymphoma in 24 cases (43.6%), Burkitt lymphoma in 12 cases (21.8%), and plasmablastic lymphoma in 5 cases (9.1%). Thirty five patients (64%) underwent curative intended chemotherapy (CT) concomitantly with highly active antiretroviral therapy (HAART). Three year survival of the whole cohort was 27%. By multivariate analysis, the most important prognostic factors for long term survival, were complete responses to CT, (p < 0.01) and a low international prognostic index (IPI) score for NHL, (p = 0.01). HAART, histologic subtype and CD4 lymphocyte count at diagnosis, did not influence survival. The most important prognostic factors for HIV patients with lymphoma, were achieving CR with CT and low IPI score. Prognosis remains poor, even with HAART therapy.


The pineal of the troglophilic fish, Chologaster agassizi: an ultrastructural study.
The pineal of the facultative, cave-dwelling fish, Chologaster agassizi, was examined electron microscopically. Two cell types, photoreceptor and supportive cells, were identified in the pineal epithelium. The photoreceptor cells had well developed outer segments and contained Golgi bodies which were surrounded by both clear and dense-cored vesicles. Vesicle-crowned rods were frequently seen in various regions of the cell. The supportive cells also contained Golgi bodies from which both clear and dense-cored vesicles appeared to originate. In addition, these cells were characterized by peculiar arrangements of the smooth endoplasmic reticulum and the presence of pigment granules. Large quantities of glycogen were observed in both cell types. Small, unmyelinated nerve fibers were seen coursing throughout the pineal epithelium. Terminals filled with pleomorphic, clear vesicles and dense-cored vesicles were present in the vicinity of these nerve fibers. Similar vesicle-filled terminals were observed in close association with the supportive cells. The results of this study indicate that the pineal in this light-deprived species is a metabolically active organ capable of photoreception. Specializations of the organelles in the pineal cells were similar to those observed in other vertebrates living in environments of low light levels.


Rapid genotyping of Plasmodium vivax Pvs25 and Pv38 genes by using mismatch specific endonuclease.
Mismatch specific endonuclease (MSE) method was used to detect natural polymorphisms in Pvs25 and Pv38 genes of Plasmodium vivax. Eighty seven patients with P. vivax were recruited in the Republic of Korea (ROK). Pvs25 and Pv38 genes were amplified by polymerase chain reaction (PCR), and the PCR amplicons were mixed with reference DNA sequences. Following the denaturation and gradual annealing, the product mixtures were cleaved by the MSE. Heteroduplex types were readily detected by gel electrophoresis, where extra bands with shorter sizes would appear from the cleavage. After MSE cleavage of 657- bp product from Pvs25 mixtures, three genotypes were detected, while Pv38 mixtures with 1220-bp products presented two genotypes in ROK isolates. After the MSE cleavage, the mismatched samples of Pvs25 and Pv38 were completely sequenced, and the results were in complete agreement with the MSE analyses. In conclusion, genotyping of Pvs25 and Pv38 with MSE cleavage could be a potential method for the high-throughput screening of the large field samples.


Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines.
To validate urinary markers for the early detection of bladder cancer (BC) in chemical workers. UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of the German Social Accident Insurance for active or retired workers with former exposure to aromatic amines. From 2003 to 2010, 1,609 men took part in voluntary annual screens. Cytology, the quantitative NMP22(®) assay, and UroVysion™ were applied to 7,091 urine samples. Fifteen out of 21 tumors were detected following test positivity. The UroVysion/NMP22 panel detected 14 out of 21 tumors versus 8 tumors with cytology alone (sensitivity 66.7 vs. 44.4 %, specificity 94.5 vs. 98.5 %). The sensitivity of the panel increased to 85.7 % in samples collected ≤12 months before diagnosis and when papillomas were excluded, compared to 58.3 % with cytology. About 3 % of NMP22 tests were false-positive. UroVysion results overlapped with cytology due to the preselection of atypical cells. NMP22 was less and UroVysion more frequently positive in diluted urine samples. Leukocytes confounded NMP22 but not UroVysion. The low incidence of BC in this study population yielded low positive predictive values of the markers and high costs per tumor detected with screening. UroVysion in combination with NMP22 detected more cases than cytology alone, at the expense of a lower specificity. High costs per detected case resulted from a lower BC incidence than in the past when levels of occupational exposure to aromatic amines were higher. Currently, it cannot be recommended to apply these markers for screening in asymptomatic workers. The increase in sensitivity is not balanced by the high costs of UroVysion and the false-positive tests of NMP22.


The pel genes of the Pseudomonas aeruginosa PAK strain are involved at early and late stages of biofilm formation.
Pseudomonas aeruginosa is a Gram-negative bacterium associated with nosocomial infections and cystic fibrosis. Chronic bacterial infections are increasingly associated with the biofilm lifestyle in which microcolonies are embedded in an extracellular matrix. Screening procedures for identifying biofilm-deficient strains have allowed the characterization of several key determinants involved in this process. Biofilm-deficient P. aeruginosa PAK strains affected in a seven-gene cluster called pel were characterized. The pel genes encode proteins with similarity to components involved in polysaccharide biogenesis, of which PelF is a putative glycosyltransferase. PelG was also identified as a putative component of the polysaccharide transporter (PST) family. The pel genes were previously identified in the P. aeruginosa PA14 strain as required for the production of a glucose-rich matrix material involved in the formation of a thick pellicle and resistant biofilm. However, in PA14, the pel mutants have no clear phenotype in the initiation phase of attachment. It was shown that pel mutations in the PAK strain had little influence on biofilm initiation but, as in PA14, appeared to generate the least robust and mature biofilms. Strikingly, by constructing pel mutants in a non-piliated P. aeruginosa PAK strain, an unexpected effect of the pel mutation in the early phase of biofilm formation was discovered, since it was observed that these mutants were severely defective in the attachment process on solid surfaces. The pel gene cluster is conserved in other Gram-negative bacteria, and mutation in a Ralstonia solanacearum pelG homologue, ragG, led to an adherence defect.


Managing nitrogen for sustainable development.
Improvements in nitrogen use efficiency in crop production are critical for addressing the triple challenges of food security, environmental degradation and climate change. Such improvements are conditional not only on technological innovation, but also on socio-economic factors that are at present poorly understood. Here we examine historical patterns of agricultural nitrogen-use efficiency and find a broad range of national approaches to agricultural development and related pollution. We analyse examples of nitrogen use and propose targets, by geographic region and crop type, to meet the 2050 global food demand projected by the Food and Agriculture Organization while also meeting the Sustainable Development Goals pertaining to agriculture recently adopted by the United Nations General Assembly. Furthermore, we discuss socio-economic policies and technological innovations that may help achieve them.


3D-printed headrest for frameless Gamma Knife radiosurgery: Design and validation.
Frameless Gamma Knife stereotactic radiosurgery (SRS) uses a moldable headrest with a thermoplastic mask for patient immobilization. An efficacious headrest is time consuming and difficult to fabricate due to the expertise required to mold the headrest within machine geometrical limitations. The purpose of this study was to design and validate a three-dimensional (3D)-printed headrest for frameless Gamma Knife SRS that can overcome these difficulties. A headrest 3D model designed to fit within the frameless adapter was 3D printed. Dosimetric properties of the 3D-printed headrest and a standard-of-care moldable headrest were compared by delivering a Gamma Knife treatment to an anthropomorphic head phantom fitted with an ionization chamber and radiochromic film. Ionization measurements were compared to assess headrest attenuation and a gamma index was calculated to compare the film dose distributions. A volunteer study was conducted to assess the immobilization efficacy of the 3D-printed headrest compared to the moldable headrest. Five volunteers had their head motion tracked by a surface tracking system while immobilized in each headrest for 20 min. The recorded motion data were used to calculate the average volunteer movement and a paired t-test was performed. The ionization chamber readings were within 0.55% for the 3D-printed and moldable headrests, and the calculated gamma index showed 98.6% of points within dose difference of 2% and 2 mm distance to agreement for the film measurement. These results demonstrate that the headrests were dosimetrically equivalent within the experimental uncertainties. Average motion (±standard deviation) of the volunteers while immobilized was 1.41 ± 0.43 mm and 1.36 ± 0.51 mm for the 3D-printed and moldable headrests, respectively. The average observed volunteer motion between headrests was not statistically different, based on a P-value of 0.466. We designed and validated a 3D-printed headrest for immobilizing patients undergoing frameless Gamma Knife SRS.


Impact of NICE guidance on tamoxifen prescribing in England 2011-2017: an interrupted time series analysis.
Tamoxifen was recommended by NICE in 2013 for chemoprevention of breast cancer, but a recent survey suggested only a quarter of GPs are aware of this. We set out to measure the uptake of tamoxifen, and the alternative raloxifene, in national prescribing data sets. Tamoxifen and raloxifene data were extracted from England's monthly prescribing data sets, October 2010-October 2017. We used interrupted time series analysis to reveal national and local responses to guidelines. We investigated variation between practices by calculating percentiles for prescribing rates and ratios of change. We found an increase in monthly tamoxifen prescribing following release of the guidelines, with an increase in gradient (p = 0.001) but no step change (p = 0.342). Alongside a small change in raloxifene prescribing we estimate 8450 women took up chemoprevention between 2013 and 2016. We did not find evidence that this was limited to a small group of practices. Our results suggest that the uptake of new guidance on chemoprevention has been slow and has potentially left women exposed to avoidable risk. Improving dissemination of guidance to healthcare professionals and routinely monitoring implementation could help reduce this risk.


Molecular basis of the osmolyte effect on protein stability: a lesson from the mechanical unfolding of lysozyme.
Osmolytes are a class of small organic molecules that shift the protein folding equilibrium. For this reason, they are accumulated by organisms under environmental stress and find applications in biotechnology where proteins need to be stabilized or dissolved. However, despite years of research, debate continues over the exact mechanisms underpinning the stabilizing and denaturing effect of osmolytes. Here, we simulated the mechanical denaturation of lysozyme in different solvent conditions to study the molecular mechanism by which two biologically relevant osmolytes, denaturing (urea) and stabilizing (betaine), affect the folding equilibrium. We found that urea interacts favorably with all types of residues via both hydrogen bonds and dispersion forces, and therefore accumulates in a diffuse solvation shell around the protein. This not only provides an enthalpic stabilization of the unfolded state, but also weakens the hydrophobic effect, as hydrophobic forces promote the association of urea with nonpolar residues, facilitating the unfolding. In contrast, we observed that betaine is excluded from the protein backbone and nonpolar side chains, but is accumulated near the basic residues, yielding a nonuniform distribution of betaine molecules at the protein surface. Spatially resolved solvent-protein interaction energies further suggested that betaine behaves in a ligand- rather than solvent-like manner and its exclusion from the protein surface arises mostly from the scarcity of favorable binding sites. Finally, we found that, in the presence of betaine, the reduced ability of water molecules to solvate the protein results in an additional enthalpic contribution to the betaine-induced stabilization.


The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats.
To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100beta protein, TNF-alpha, and IL-1beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na(+)-K(+)-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100beta, TNF-alpha, and IL-1beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.


A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo.
There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV(1). The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting >/= 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV(1) decline in COPD patients, and whether this relationship is modified by gender and smoking. There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (+/- SE) relative increase in FEV(1) of 2.42 +/- 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV(1) decline (-0.01 +/- 0.09%; p = 0.86). The initial treatment effect was dependent on smoking status and gender. Smokers who continued to smoke had a smaller increase in FEV(1) during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV(1) with ICS therapy than did male ex-smokers. We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV(1) among those who completed these randomized clinical trials.


Knowledge, beliefs, and attitudes of older women in HIV/AIDS prevention.
To analyze the knowledge, religious beliefs and the adoption of preventive measures against HIV/AIDS of non-Catholic elderly women. A qualitative study, carried out in religious institutions of a municipality in the state of Ceará, Northeast Brazil, with 78 elderly women. Of these, 64 were evangelicals, seven spiritualists and seven Jehovah's Witnesses. A semi-structured interview script was used followed by thematic content analysis of participants' responses. After analyzing the empirical data, three categories were elaborated: the first presented the knowledge they had about AIDS; the second, highlighted the beliefs attributed to people with HIV/AIDS; and the third, presented the preventive measures to HIV/AIDS adopted by them. There were participants with knowledge gaps and failure to use preventive measures against HIV/AIDS. They suggested that religious institutions can be venues for lectures on HIV/AIDS prevention.


Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation.
Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed.


Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease.
Since the histological expression of galectins is increased in thyroid carcinoma, determination of their serum levels may provide useful preoperative information. The goal of this study was to determine if a difference in galectin serum levels could be detected between benign and malignant nodular thyroid diseases. Using validated ELISAs, the concentrations of several galectins were prospectively measured in serum samples from 30 healthy individuals and preoperatively in 90 patients with thyroid disease. Seventy-one patients had multiple thyroid nodules (MTN), 13 patients had a single thyroid nodule (STN), and 6 patients had Graves' disease. Nine of 71 patients with MTN had fine-needle aspiration biopsy (FNAB) of their nodules and in 7 patients a "benign" diagnosis was made, in 0 patient a "malignant" diagnosis was made, and in 2 patients a "suspicious" diagnosis was made. Six of 13 patients with STN had FNAB of their nodules and in 2 patients a "benign" diagnosis was made, in 3 patients a "malignant" diagnosis was made, and in 1 patient a "suspicious" diagnosis was made. Thyroid disease was associated with higher levels of galectins-1 and -3 compared to normal subjects. Using a threshold value of 3.2 ng/mL as a cut-off point, the measurement of serum galectin-3 separated micro- and macropapillary thyroid carcinoma (PAP_CA) from patients with nonmalignant thyroid disease with 74% specificity, 73% sensitivity, 57% positive predictive value, and 85% negative predictive value. Elevated serum galectin-3 concentrations (>3.2 ng/mL) detected 87% of macropapillary thyroid carcinomas and 67% of micropapillary thyroid carcinomas. Serum levels of galectins-1 and -3 are relatively high in patients with thyroid malignancy but there is considerable overlap in serum galectin-3 concentrations between those with benign and malignant nodular thyroid disease and, to a lesser extent, between those with and without nodular thyroid disease.


Penetrance estimates for BRCA1, BRCA2 (also applied to Lynch syndrome) based on presymptomatic testing: a new unbiased method to assess risk?
The identification of BRCA1, BRCA2 or mismatch repair (MMR) pathogenic gene variants in familial breast/ovarian/colorectal cancer families facilitates predictive genetic testing of at-risk relatives. However, controversy still exists regarding overall lifetime risks of cancer in individuals testing positive. We assessed the penetrance of BRCA1, BRCA2, MLH1 and MSH2 mutations in men and women using Bayesian calculations based on ratios of positive to negative presymptomatic testing by 10-year age cohorts. Mutation position was also assessed for BRCA1/BRCA2. RESULTS: Using results from 2264 presymptomatic tests in first-degree relatives (FDRs) of mutation carriers in BRCA1 and BRCA2 and 646 FDRs of patients with MMR mutations, we assessed overall associated cancer penetrance to age of 68 years as 73% (95% CI 61% to 82%) for BRCA1, 60% (95% CI 49% to 71%) for BRCA2, 95% (95% CI 76% to 99%) for MLH1% and 61% (95% CI 49% to 76%) for MSH2. There was no evidence for significant penetrance for males in BRCA1 or BRCA2 families and males had equivalent penetrance to females with Lynch syndrome. Mutation position and degree of family history influenced penetrance in BRCA2 but not BRCA1. CONCLUSION: We describe a new method for assessing penetrance in cancer-prone syndromes. Results are in keeping with published prospective series and present modern-day estimates for overall disease penetrance that bypasses retrospective series biases.


Success rates of primary probing for congenital nasolacrimal obstruction in children.
To determine the success rate of nasolacrimal duct probing for the treatment of congenital nasolacrimal duct obstruction and to identify the age at which the success rate decreases. Records for probing procedures from 2005 to 2010, over a 56-month period, were reviewed. Successful probing was defined as complete resolution of epiphora 3 months after treatment. Success rates were compared between children <3 years of age and children ≥3 years of age at the time of the procedure. A total of 168 eyes (128 children, mean age 32.2 ± 23.8 months) had undergone a probing procedure, and the overall success rate was 72%. Children aged <36 months had a success rate of 78%; children aged ≥36 months had a success rate of 50%. Multivariate analysis demonstrated that age at the time of procedure was a significant risk factor for failed probing (P = 0.035; OR, 1.67; 95% CI, 1.04-2.69), whereas sex and bilateral surgery were not. The success rate of primary probing for congenital nasolacrimal duct obstruction was significantly reduced when performed on children ≥3 years of age.


The extent of synaptic stripping of motoneurons after axotomy is not correlated to activation of surrounding glia or downregulation of postsynaptic adhesion molecules.
Synapse elimination in the adult central nervous system can be modelled by axotomy of spinal motoneurons which triggers removal of synapses from the cell surface of lesioned motoneurons by processes that remain elusive. Proposed candidate mechanisms are removal of synapses by reactive microglia and astrocytes, based on the remarkable activation of these cell types in the vicinity of motoneurons following axon lesion, and/or decreased expression of synaptic adhesion molecules in lesioned motoneurons. In the present study, we investigated glia activation and adhesion molecule expression in motoneurons in two mouse strains with deviant patterns of synapse elimination following axotomy. Mice deficient in complement protein C3 display a markedly reduced loss of synapses from axotomized motoneurons, whereas mice with impaired function of major histocompatibility complex (MHC) class Ia display an augmented degree of stripping after axotomy. Activation of microglia and astrocytes was assessed by semiquantative immunohistochemistry for Iba 1 (microglia) and GFAP (astrocytes), while expression of synaptic adhesion molecules was determined by in situ hybridization. In spite of the fact that the two mouse strains display very different degrees of synapse elimination, no differences in terms of glial activation or in the downregulation of the studied adhesion molecules (SynCAM1, neuroligin-2,-3 and netrin G-2 ligand) could be detected. We conclude that neither glia activation nor downregulation of synaptic adhesion molecules are correlated to the different extent of the synaptic stripping in the two studied strains. Instead the magnitude of the stripping event is most likely a consequence of a precise molecular signaling, which at least in part is mediated by immune molecules.


Retirement plan participation and features and standard of living of Americans 55 or older.
This Issue Brief is the third in a series of Employee Benefit Research Institute (EBRI) publications based on data collected in 1998 and released in 2002 as the Retirement and Pension Plan Coverage Topical Module of the 1996 Survey of Income and Program Participation (SIPP). This report completes the series by examining the survey's more detailed questions concerning workers' employment-based retirement plans. Specifically, it examines the percentage of workers who are participating in a plan, and also workers' reasons for not participating in a plan when working in a job where a plan is sponsored; the features of, or decisions made concerning salary reduction plans; historical participation in employment-based retirement plans; and a comparison of the standard of living of individuals age 55 or older with their living standard in their early 50s. As of June 1998, 64.3 percent of wage and salary workers age 16 or older worked for an employer or union that sponsored any type of retirement plan (defined contribution or defined benefit) for any of its employees or members (the "sponsorship rate"). Almost 47 percent of these wage and salary workers participated in a plan (the "participation rate"), with 43.2 percent being entitled to a benefit or eligible to receive a lump-sum distribution from a plan if their job terminated at the time of survey (the "vested rate"). The predominant reason for choosing not to participate in a retirement plan was that doing so was unaffordable. The eligible participation rate for salary reduction plans was 81.4 percent. Fifty-six percent of all workers have participated in some type of retirement plan sometime during their work life through 1998. For those ages 51-60, almost 72 percent have ever participated in a plan. The median account balance in salary reduction plans in 1998 was $14,000. In 1998, 12.9 percent of salary reduction plan participants eligible to take a loan had done so, and the average outstanding loan balance was $5,196. Nearly 80 percent of those age 55 or older reported that their standard of living is about the same or better now than it was when they were in their early 50s. The incidence of both pension income and health insurance from a former employer had a significant impact on retirees' ability to maintain their standard of living. In addition, those who spent their entire most recent lump-sum distribution were more likely to have a much worse standard of living in retirement than those who rolled over their entire most recent distribution.


Soliton transverse instabilities in anisotropic nonlocal self-focusing media.
We study, both numerically and experimentally, the transverse modulational instability of spatial stripe solitons in anisotropic nonlocal photorefractive media. We demonstrate that the instability scenarios depend strongly on the stripe orientation, but the anisotropy-induced features are largely suppressed for spatial solitons created by self-trapping of partially incoherent light.


Depression symptoms improve after successful weight loss with emotional freedom techniques.
Ninety-six overweight or obese adults were randomly allocated to a four-week EFT treatment or waitlist condition. Waitlist participants crossed over to the EFT group upon completion of wait period. Degree of food craving, perceived power of food, restraint capabilities, and psychological symptoms were assessed at pretreatment, posttreatment and at 12-month follow-up for combined EFT groups. Significant improvements in weight, body mass index, food cravings, subjective power of food, craving restraint and psychological coping for EFT participants from pretreatment to 12-month follow-up (P < 0.05) were reported. The current paper isolates the depression symptom levels of participants, as well as levels of eight other psychological conditions. Significant decreases from pre- to posttreatment were found for depression, interpersonal sensitivity, obsessive-compulsivity, paranoid ideation, and somatization (P < 0.05). Significant decreases from pretreatment to 12-month follow-up were found for depression, interpersonal sensitivity, psychoticism, and hostility. The results point to the role depression, and other mental health conditions may play in the successful maintenance of weight loss.


Human Epidermal Growth Factor 2-positive Breast Cancer with Mammographic Microcalcification: Relationship to Pathologic Complete Response after Neoadjuvant Chemotherapy.
Purpose To determine the relationship between the presence or absence of mammographic calcifications in human epidermal growth factor receptor 2 (HER2)-positive breast cancers and pathologic complete response (pCR) to neoadjuvant chemotherapy and to determine other tumor and clinical characteristics that may be predictive of such a response. Materials and Methods A database of all patients with HER2-positive breast cancer who underwent neoadjuvant chemotherapy between 2007 and 2015 was retrospectively reviewed. Patient demographic characteristics, mammographic appearance, molecular subtype of cancer (luminal or nonluminal), radiologic response (based on breast magnetic resonance images), surgery, and pathologic response to treatment were recorded. Inter- and subgroup comparison was performed for presence of mammographic microcalcification and cancer subtype by using Mann-Whitney and χ2 tests and logistic regression. Results A total of 111 patients with a median age of 49 years (interquartile range, 40-57 years) were evaluated. Of these, 64.9% (72 of 111) had mammographic microcalcifications, 63.1% (70 of 111) had luminal B cancer, and 36.9% (41 of 111) had nonluminal HER2-positive cancer. Radiologic response to neoadjuvant chemotherapy was observed in 70.3% (78 of 111) of patients. Surgery was performed in 97.3% (108 of 111) of patients, and 30.6% (34 of 111) of patients underwent breast conservation. pCR was observed in 33.3% (37 of 111) of patients; 16.2% (18 of 111) showed residual ductal carcinoma in situ and 50.5% (56 of 111) had residual invasive disease. The pCR rate was the same (P = .21) in patients with mammographic microcalcification (29.2% [21 of 72]) as in those without calcification (41.0% [16 of 39]). The pCR rate in patients with nonluminal HER2-positive cancers (46.3% [19 of 41]) was higher (P = .01) than in those with luminal B cancers (25.7% [18 of 70]). pCR was associated with nonluminal HER2-positive subtype (odds ratio, 5.4; 95% confidence interval: 1.8, 16.0; P = .01) and complete radiologic response (odds ratio, 20.4; 95% confidence interval: 3.3, 126.6; P = .01). Conclusion Patients with HER2-positive cancer and mammographic microcalcification can achieve pCR after neoadjuvant chemotherapy. Nonluminal HER2-positive subtype and complete radiologic response are predictors of pCR.


Results of treatment of malignant soft tissue tumours in the groin.
Soft tissue sarcomas of the inguinal region are a challenge with regard to achieving clear margins, reconstruction of the femoral vessels, and soft tissue coverage. Six men aged 39 to 48 years and one woman of 56 were treated for soft tissue sarcomas of the groin. All patients were treated with local en bloc resections including the femoral artery, vein, and nerve. In two patients the soft tissue defect was covered primarily with an ipsilateral rectus abdominis muscle flap, in two others (because of wound dehiscence) coverage was achieved with the opposite rectus abdominis muscle pedicle flap as we were afraid of closure of the ipsilateral deep epigastric vessels. In the others local measures were sufficient, however, wound healing was usually delayed. Histopathological examination showed tumour-free margins in each case. One patient developed a local recurrence, but had had no radiotherapy because of problems with wound healing. A high rate of local tumour control in soft tissue sarcomas of the inguinal region can be achieved with the combination of surgical resection and radiotherapy. No compromise should be made with aggressive soft tissue coverage to protect the vascular reconstruction, control wound healing after neoadjuvant radiotherapy, or allow immediate adjuvant radiotherapy. At primary wound closure we would generally use an ipsilaterally distally pedicled rectus abdominis muscle flap if the deep epigastric vessels can be preserved or - if the ipsilateral vessels need be resected to achieve clearance of tumour - use a contralateral flap.