Psychological Interventions Can Reduce Injury Risk in Athletes: A Critically Appraised Topic.
Clinical Scenario: Injury prevention programs are becoming standard practice for reducing sports-related injuries, but most programs focus on musculoskeletal elements. Psychological factors can be strong predictors of sports-related injuries and there is recent evidence that suggests psychological interventions can be effective at reducing injury risk. It is unclear if injury prevention programs that focus on psychological factors are an important inclusion for athletic trainers/therapists. Athletes can be exposed to different psychological factors based on sport type including team or individual sports, which can increase their risk of injury. While psychological interventions can reduce injuries by addressing psychological symptoms, it is unclear if the interventions are effective for at-risk athletes in addition to athletes who are not suffering from any psychological factors. Currently, there are no guidelines or recommendations for athletic trainers/therapists to address psychological factors with the purpose of injury prevention. Clinical Question: Are psychological intervention programs effective in reducing sports-related injury risk and are they clinically relevant to athletic trainers/therapists for implementation in all settings? Summary of Findings: The authors searched the literature for studies investigating the use of psychological intervention programs to reduce sports-related injuries in an athletic population. The search returned 6 possible papers (2 systematic reviews without meta-analysis, 1 systematic review with a meta-analysis, 2 meta-analyses, and 1 randomized control trial not included in the systematic reviews). The authors narrowed our appraisal to one systematic review and one randomized controlled trial. The review contained all the studies from the previous review papers including 3 studies which performed screening procedures. The collection of evidence demonstrates positive effects associated with implementing psychological intervention techniques to reduce sports injury rates in all athletes; at-risk athletes, not at-risk athletes, and individual and team-sport athletes. Bottom Line: There is sufficient evidence supporting the use of a psychological-based intervention by athletic trainers/therapists to effectively reduce the number of injury occurrences in the athletic population. Direct comparisons of effectiveness between team and individual sports was not conducted in the research, but a substantial representation of both sport types existed. The current evidence includes a variety of athletic populations, at-risk and not at-risk, different sport types, and competition levels. Athletic trainers/therapists should consider the integration of psychological disciplines in current injury prevention practices to address the psychological concerns which put athletes at additional risk for injury. Strength of Recommendation: Grade B evidence exists to support the use of psychological intervention strategies in a well-developed injury prevention plan. Sports medicine practitioners can help athletes reduce stress, increase mindfulness, and be more aware of mental health practices which helps reduce injury risk.


Stereochemistry and deuterium isotope effects in camphor hydroxylation by the cytochrome P450cam monoxygenase system.
Bacterial cytochrome P450cam catalyzes the hydroxylation of camphor to yield 5-exo-hydroxycamphor in vivo and in a reconstituted system with oxygen, pyridine nucleotide, flavoprotein dehydrogenase, and putidaredoxin. Product is also formed when the ferric form of the hemoprotein is mixed with the exogenous oxidants iodosobenzene, m-chloroperbenzoic acid, and hydrogen peroxide. In this paper we show that when the P450cam-dependent hydroxylation reactions are studied with camphor analogues containing deuterium at either the 5-exo or 5-endo position, a very small intermolecular isotope on the overall reaction velocity is observed and a significant intramolecular isotope effect is documented. We suggest the existence of an intermediate substrate-carbon radical and demonstrate that abstraction can occur from either the exo or endo position at carbon 5 on the camphor skeleton, with the oxygen stereospecifically added to only the Re face to give 5-exo-hydroxycamphor as the unique product. Using these substrates, we observed nearly identical hydrogen/deuterium isotope ratios in the product alcohol for the pyridine nucleotide/atmospheric dioxygen as well as exogenous oxidant supported hydroxylations, suggesting that these reactions share a common hydrogen-abstracting species. The relatively small magnitude of the measured intramolecular isotope effect can be rationalized with a model involving a reversible hydrogen-abstraction step and/or the involvement of heavy-atom motion in the reaction coordinate.


Intracellular translocation of PKC isoforms in canine pulmonary artery smooth muscle cells by ANG II.
Our goals were to identify the isoforms of protein kinase C (PKC) present in primary cultures of canine pulmonary artery smooth muscle cells (PASMCs) and to determine whether angiotensin II (ANG II) triggers translocation of specific PKC isoforms to discreet intracellular locations. Isoform-specific antibodies and Western blot analysis were utilized to identify the isoforms of PKC in PASMCs. Indirect immunofluorescence and confocal microscopy were used to examine the subcellular distribution of PKC isoforms. Inositol phosphate production was used to assess phospholipase C activation, and fura 2 was utilized to monitor intracellular Ca2+ concentration in response to ANG II. Six isoforms (alpha, delta, epsilon, zeta, iota/lambda, and mu) of PKC were identified by Western blot analysis. Immunolocalization of 5 isoforms (alpha, delta, zeta, iota/lambda, and mu) revealed a unique pattern of staining for each individual isoform. ANG II caused translocation of PKC-alpha from the cytosol to the nuclear envelope and of PKC-delta to the myofilaments. In contrast, cytosolic PKC-zeta did not translocate, but nuclear PKC-zeta was upregulated. Translocation of PKC-alpha and PKC-delta and upregulation of PKC-zeta in response to ANG II were blocked by the ANG II type 1-receptor antagonist losartan. In addition, ANG II stimulated inositol phosphate production and intracellular Ca2+ concentration oscillations, which were blocked by losartan. Thus activation of ANG II type 1 receptors triggers the phosphoinositide signaling cascade, resulting in translocation or upregulation of specific PKC isoforms at discreet intracellular sites. The alpha and zeta isoforms may act to regulate nuclear events, whereas PKC-delta may be involved in modulating contraction via actions on the myofilaments.


Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study.
A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate. A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate. 301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur). Patients who were previously stable on doses of brand alendronate experienced an increase in AEs causing discontinuation after introduction of automatic substitution to generic alendronate. In addition, reductions in BMD were observed in some patients who had stable BMDs before January 2006. Given the substantial increase in AEs, generic alendronate may not be as well tolerated as brand alendronate.


The use of smartphones for clinical communication on internal medicine wards.
Communication between clinicians is hampered by the frequent difficulty in reaching the most responsible physician for a patient as well as the use of outdated methods such as numeric paging. The aim of this study was to evaluate the use of smartphones to improve communication on internal medicine wards. At the Toronto General Hospital, residents were provided with smartphones. To simplify reaching the most responsible resident for a patient, a smartphone designated as "Team BlackBerry" was also carried by each senior resident and then passed to the resident covering the team at night and on weekends. Nurses were able to send email messages or call smartphones directly. There were on average of 9.1 incoming calls, 6.6 outgoing calls, 14.3 received emails, and 2.8 sent emails per day to each Team BlackBerry. Team BlackBerrys received up to 35 calls and 57 emails per day. Residents strongly preferred the smartphones over conventional paging with perceived improvements in all items measured and felt that it improved efficiency and communication. Although nurses perceived a reduction in the time required to contact a physician (27.6 vs. 11 minutes P < 0.001), their overall satisfaction with physician's response time for urgent issues did not improve significantly. When smartphones were used for clinical communication, residents perceived an improvement in communication with them. Residents strongly preferred emails as opposed to telephone calls as the prime method of communication. Further objective evaluation is necessary to determine if this intervention improves efficiency and more importantly, quality of care.


Behavioral competencies for nursing practice.
As a part of its unsuccessful attempt to standardize nursing education in 1987, an Illinois Nurses' Association task force developed behavioral competency statements describing performance standards for two levels of nursing practice. But because of fear of further divisiveness, these statements were "hidden under a bushel"--until now.


Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 14 - effects of different classes of antihypertensive drugs in older and younger patients: overview and meta-analysis.
The five major classes of blood pressure (BP)-lowering drugs have all been shown to significantly reduce the risk of major cardiovascular events when compared with placebo, and when directly (head-to-head) compared, no significant differences in their overall effectiveness have been detected, except for minor differences in cause-specific events. It is unknown, however, whether age-related differences exist and if some classes of drugs are differently effective in older or younger individuals. This clinically relevant question has been the object of a systematic search and meta-analysis of all available data. Two databases we had previously identified [72 placebo-controlled BP-lowering randomized clinical trials (RCTs) in 260 210 individuals and 50 RCTs head-to-head comparing treatments with BP-lowering drugs of different classes in 247 006 individuals) were searched for separately reported data on patients older or younger than 65 years, and the data were further stratified according to the class of drug [diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers] compared with placebo or with other drug classes. Seven fatal and nonfatal outcomes were considered for benefits. Adverse events were investigated as permanent treatment discontinuations for adverse events. Risk ratios and absolute risk changes were calculated by a random effects model. Effects at older and younger ages were compared by heterogeneity test. We identified 20 placebo-controlled RCTs on 55 645 older individuals and 21 on 99 621 younger individuals, and 21 head-to-head drug comparison RCTs on 94 228 older individuals and 27 on 100 232 younger individuals (for a total of 349 726 individuals). When compared with placebo, all five classes of BP-lowering drugs significantly reduced the risk of major cardiovascular events or stroke, with no significant difference between older and younger patients. However, in head-to-head comparisons, no significant difference was found between older and younger patients in the effects of diuretics, calcium antagonists, ACE inhibitors and angiotensin receptor blockers on all cardiovascular outcomes, whereas beta-blockers revealed an age-dependent effectiveness, being equally effective as the other agents at an age below 65 years, but less effective at an older age. Most BP-lowering classes are equally effective in preventing risk of fatal and nonfatal cardiovascular events both in older and younger patients, whereas beta-blockers, though being equally effective as the other agents in patients younger than 65, loose some of their effectiveness at an older age.


Computational analysis of retrovirus-induced scid cell death.
It was shown recently that retroviral infection induces integrase-dependent apoptosis (programmed cell death) in DNA-dependent protein kinase (DNA-PK)-deficient scid pre-B cell lines, and it has been proposed that retroviral DNA integration is perceived as DNA damage that is repairable by the DNA-PK-dependent nonhomologous end-joining pathway (R. Daniel, R. A. Katz, and A. M. Skalka, Science 284:644-647, 1999). Very few infectious virions seem to be necessary to induce scid cell death. In this study, we used a modeling approach to estimate the number of integration events necessary to induce cell death of DNA-PK-deficient scid cells. Several models for integration-mediated cell killing were considered. Our analyses indicate that a single hit (integration event) is sufficient to kill a scid cell. Moreover, the closest fit between the experimental data and our computational simulations was achieved with a model in which the infected scid cell must pass through S phase to trigger apoptosis. This model is consistent with the findings that a single double-strand DNA break is sufficient to kill a cell deficient in DNA repair and illustrates the potential of a modeling approach to address quantitative aspects of virus-cell interactions.


Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor-derived SRSRY peptide.
The urokinase-type plasminogen activator receptor (uPAR) sustains cell migration through its capacity to promote pericellular proteolysis, regulate integrin function, and mediate chemotactic signaling in response to urokinase. We have characterized the early signaling events triggered by the Ser-Arg-Ser-Arg-Tyr (SRSRY) chemotactic uPAR sequence. Cell exposure to SRSRY peptide promotes directional migration on vitronectin-coated filters, regardless of uPAR expression, in a specific and dose-dependent manner, with maximal effect at a concentration level as low as 10 nm. A similar concentration profile is observed in a quantitative analysis of SRSRY-dependent cytoskeletal rearrangements, mostly consisting of filamentous structures localized in a single cell region. SRSRY analogues with alanine substitutions fail to drive F-actin formation and cell migration, indicating a critical role for each amino acid residue. As with ligand-dependent uPAR signaling, SRSRY stimulates protein kinase C activity and results in ERK1/2 phosphorylation. The involvement of the high affinity N-formyl-Met-Leu-Phe receptor (FPR) in this process is indicated by the finding that 100 nm N-formyl-Met-Leu-Phe inhibits binding of D2D3 to the cell surface, as well as SRSRY-stimulated cell migration and F-actin polarization. Moreover, cell exposure to SRSRY promotes FPR-dependent vitronectin release and increased uPAR.alphavbeta5 vitronectin receptor physical association, indicating that alphavbeta5 activity is regulated by the SRSRY uPAR sequence via FPR. Finally, we provide evidence that alphavbeta5 is required for SRSRY-dependent ERK1/2 phosphorylation, whereas it is not required for protein kinase C activation. The data indicate that the ability of uPAR to stimulate cell migration and cytoskeletal rearrangements is retained by the SRSRY peptide alone and that it is supported by cross-talk between FPR and alphavbeta5.


Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells.
There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN), the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs) as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05). The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011). The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05), demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.


Multigenerational programming in the glucocorticoid programmed rat is associated with generation-specific and parent of origin effects.
Exposure to an adverse early life environment is associated with increased cardio-metabolic disease risk, a phenomenon termed "programming." The effects of this are not limited to the exposed first (F1) generation but can be transmissible to a second generation (F2) through male and female lines. Using a three generation animal model of programming by initial prenatal glucocorticoid overexposure we have identified effects on fetal and placental weight in both the F1 and F2 offspring. However, the expression of candidate imprinted genes in the fetus and placenta differed between the F1 and F2, with marked parent-of-origin effects in F2. Since DNA methylation at imprinted genes is maintained at fertilization, they are potential templates for the transmission of programming effects across generations. Although we detected alterations in DNA methylation at differentially methylated regions (DMRs) of the key prenatal growth factor Igf2 in F1 and F2 fetal liver, the changes in DNA methylation at these DMRs do not appear to underlie the transmission of effects on Igf2 expression through sperm. Thus, multigenerational programming effects on birth weight and disease risk is associated with different processes in F1 and F2. These findings have implications for the pathogenesis and future attempts to stratify therapies for the "developmental component" of cardiometabolic disease.


Object representations in visual memory: evidence from visual illusions.
Human visual memory is considered to contain different levels of object representations. Representations in visual working memory (VWM) are thought to contain relatively elaborated information about object structure. Conversely, representations in iconic memory are thought to be more perceptual in nature. In four experiments, we tested the effects of two different categories of visual illusions on representations in VWM and in iconic memory. Unlike VWM that was affected by both types of illusions, iconic memory was immune to the effects of within-object contextual illusions and was affected only by illusions driven by between-objects contextual properties. These results show that iconic and visual working memory contain dissociable representations of object shape. These findings suggest that the global properties of the visual scene are processed prior to the processing of specific elements.


Platelet-activating factor stimulation of tyrosine kinase and its relationship to phospholipase C in rabbit platelets: studies with genistein and monoclonal antibody to phosphotyrosine.
Platelet-activating factor (PAF) is a proinflammatory lipid that has platelet-stimulating property. PAF receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) and phosphorylation of several proteins has already been established in our laboratory. To investigate further the molecular mechanism and relationship between activation of PLC and protein phosphorylation, we have used Genistein (a putative inhibitor of tyrosine-specific protein kinases), phosphotyrosine antibody, and phosphoamino acid analysis to probe the involvement of tyrosine kinase in this process. Washed rabbit platelets were loaded with myo-[2-3H]inositol and challenged with PAF (100 nM) after pretreatment with Genistein. PLC-mediated production of radioactive inositol monophosphate, inositol diphosphate, and inositol triphosphate was monitored. PAF alone caused stimulation of PLC activity [( 3H]inositol triphosphate production), whereas pretreatment with Genistein (0.5 mM) diminished PAF-stimulated PLC activity to basal level. Genistein also blocked PAF-stimulated platelet aggregation at this dose. In contrast to Genistein, staurosporine which inhibits protein kinase C, potentiated PAF-stimulated [3H]inositol triphosphate production. Genistein substantially inhibited the combined effects of staurosporine and PAF on inositol triphosphate production. Genistein also reduced PAF-induced phosphorylation of Mr 20,000 and 50,000 proteins. Phorbol 12-myristate 13-acetate-induced Mr 40,000 protein phosphorylation was also affected by Genistein. The above results suggested that Genistein inhibited tyrosine kinase at an early stage of signal transduction by inhibiting PLC. This, in turn, decreased the activation of protein kinase C and, therefore, caused a reduction in Mr 40,000 protein phosphorylation. The inhibition of PLC by Genistein raised the possibility of involvement of tyrosine kinase in PAF receptor-coupled PLC activation. Western blot analysis using monoclonal antibody to phosphotyrosine demonstrated that PAF stimulated the tyrosine phosphorylation of two major proteins of 50,000 and 60,000 molecular weight. When platelets were challenged with PAF after treatment with either Genistein or CV-6209 (a PAF receptor antagonist), the reactivity of these proteins to monoclonal antibody was inhibited. Phosphoamino acid analysis of Mr 50,000 and 60,000 proteins confirmed that PAF increased the phosphorylation of tyrosine residues in both Mr 50,000 and 60,000 proteins and that this was inhibited by Genistein. Thus, PAF caused a receptor-dependent phosphorylation of tyrosine residues on Mr 50,000 and 60,000 proteins. Based on these observations, it is concluded that tyrosine kinase is involved in the PAF receptor-coupled PLC activation and signal transduction mechanism.


P2X7 receptor and cytokines contribute to extra-territorial facial pain.
The whisker pad area (WP) is innervated by the second branch of the trigeminal nerve and experiences allodynia and hyperalgesia following transection of the mental nerve (MN; the third branch of the trigeminal nerve). However, the mechanisms of this extra-territorial pain remain unclear. The ionotropic P2X(7) ATP receptor (P2X(7)) in microglia is known to potentiate, via cytokines, the perception of noxious stimuli, raising the possibility that P2X(7) and cytokines are involved in this extra-territorial pain. One day after MN transection (MNT), WP allodynia/hyperalgesia developed, which lasted for > 8 wks. Activation of microglia and up-regulation of P2X(7), membrane-bound tumor necrosis factor (TNF)-α (mTNF-α), and soluble TNF-α (sTNF-α) in the trigeminal sensory nuclear complex (TNC) were evident for up to 6 wks after MNT. Allodynia/hyperalgesia after MNT was blocked by intracisternal administration of etanercept, a recombinant TNF-α receptor (p75)-Fc fusion protein. Intracisternal A438079, a P2X(7) antagonist, also attenuated allodynia/hyperalgesia and blocked up-regulation of mTNF-α and sTNF-α in the TNC. We conclude that sTNF-α released by microglia following P2X(7) activation may be important in both the initiation and maintenance of extra-territorial pain after MNT.


Hospitalizations and mortality in systemic sclerosis: results from the Nationwide Inpatient Sample.
To study the causes of hospitalizations and predictors of subsequent adverse outcomes for contemporary cohorts of patients with systemic sclerosis (SSc) in the USA. The data source was the 2002 and 2003 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) databases. We identified all discharges with an International Classification of Diseases-Clinical Modification (ICD9-CM) code of 710.1 (limited and diffuse SSc), then excluded those with concomitant diagnoses for lupus or rheumatoid arthritis. We calculated hospitalization rates, in-hospital mortality rates and mean length of stay (LOS). Multivariate logistic and linear regression models for in-hospital death and LOS were performed adjusting for sociodemographic and comorbidity covariates. The overall in-hospital mortality rate was 6.3% and the mean LOS was 6.6 days. Hospitalization rates were 4.5 times higher in women than in men, but in-hospital mortality was approximately 25% lower (P = 0.005). SSc was the most common principal diagnosis for all SSc hospitalizations, with the most common secondary diagnosis (24%) being pulmonary fibrosis. After SSc, respiratory failure was the second most common principal diagnosis in patients who died. Pulmonary fibrosis increased the odds of in-hospital death by 2.63 [95% confidence interval (CI) 1.98-3.49] fold and increased LOS by 7.25% (95% CI 0.90-13.60). Women with SSc had higher rates of hospitalization but lower in-hospital mortality than men. Pulmonary fibrosis was the major predictor of poor hospitalization outcomes in SSc patients in recent years, emphasizing the importance of continuing to develop more effective therapies for this fatal complication of the disease.


The immunophenotype of ependymomas.
The morphologic distinction of ependymomas with epithelial cytology from metastatic carcinoma may pose a significant problem in differential diagnosis. The known presence of keratin in glioma cells further complicates the issue. Using the labeled streptavidin-biotin method with automated staining, we studied epithelial and glial marker expression in 52 ependymomas of varying type and grade, including 20 epithelial-appearing, 14 glial-appearing, eight mixed pattern, and 10 myxopapillary tumors; 38 were low grade and 14 anaplastic. All tumors were immunoreactive for glial fibrillary acidic protein (GFAP), and S-100 protein. Diffuse staining for GFAP was noted in glial-appearing ependymomas featuring perivascular pseudorosettes. Diffuse immunostaining for S-100 protein was seen in cellular lesions exhibiting epithelial-like features. Staining was more diffuse for GFAP than S-100 protein in anaplastic ependymomas. Keratin (AE1/AE3) reactivity was seen in 98% of cases, the pattern being similar to that of GFAP. The frequency of staining for other keratins varied: wide-spectrum keratin (35%), cytokeratin (CK)7 (20%), CAM 5.2 (19%), CK903 (14%), and CK20 (8%); as a rule, it was scant and limited to occasional cells and processes. epithelial membrane antigen (EMA) staining was seen in 36% of all cases and in 67% of epithelial-appearing tumors wherein it often high-lighted microlumina. Aside from AE1/AE3 staining and very infrequent wide-spectrum keratin and EMA reactivity, expression of epithelial markers was not seen in anaplastic ependymomas. No carcinoembryonic antigen (CEA) positivity was noted in any case. Collagen IV reactivity was limited to tumor cell-stroma interfaces. Although variable, S-100 protein and GFAP staining is seen in all ependymomas, particularly in true and perivascular pseudorosettes. Widespread reactivity for keratin AE1/AE3 corresponds closely to the pattern of GFAP staining. Significant staining for other keratins or for CEA is inconsistent with a diagnosis of ependymoma. EMA reactivity is largely limited to luminal staining of rosettes and tubules.


[Neonatal ascites: meconium ileus with perforation in mucoviscidosis].
Many conditions are known associated with neonatal ascites such as cardiac and vascular malformations, as well as malformations of the brain, kidney, lung and bone, chromosomal abnormalities, infections, fetal anemias, tumors, metabolic and maternal conditions. In 30% no reason can be found. Meconium ileus is a causal gastrointestinal abnormality. We report about a preterm infant 35 weeks of gestation with complicated meconium ileus because of mucoviscidosis.


[Intramedullary epidermoid cyst. Contribution of magnetic resonance imaging].
Epidermoid tumors are seldom found as a cause of spinal cord compression; still fewer involve the spinal cord itself. We report a case of a thoracic intramedullary epidermoid tumor documented by MRI.


High incidence of non-upper aerodigestive primary tumors in patients with esophageal cancer.
Earlier reports have described an association between esophageal cancer (EC) and high incidence of other primary tumors (OPTs) of the upper aerodigestive tract and breast cancer. We evaluated the incidence of non-upper aerodigestive OPTs among Israeli EC patients; 2328 EC patients were retrieved from the Israeli National Cancer Registry between 1980 and 2004. The relative risk of OPTs for EC patients was measured using standardized incidence ratio (SIR). Two cohorts, Israeli National Cancer Registry registered colorectal cancer (CRC) patients and the general Israeli population, were used for reference; 297 EC patients (12.7%) had OPTs, including breast (18.9%), CRC (16.2%), prostate (8.8%), and bladder (8.4%) cancers. Upper aerodigestive OPTs were less common. Most OPTs were identified before (74.4%) or simultaneously with (13.8%) EC diagnosis. The median time interval between OPTs diagnoses and EC development was 6.0 years. The incidence of OPTs was significantly higher among EC patients compared with CRC patients (SIR: 2.05, P < 0.01) or the general Israeli population (SIR: 3.90, 95% CI: 3.46-4.34, P < 0.01) regardless of gender or tumor histology. Patients with EC have high incidence of non-upper aerodigestive malignancies. Unlike previous reports, the distribution of OPTs in EC seems to represent the relative incidences of these cancers in the western populations.


Switching to Intranasal Esketamine Maintains the Antidepressant Response to Intravenous Racemic Ketamine Administration: A Case Series of 10 Patients.
This study aims to assess the efficacy and safety of intranasal (IN) esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous (IV) racemic ketamine for treatment-resistant depression (TRD). This is a retrospective case series of 10 consecutive outpatients with TRD who all had a clinically meaningful response when treated with IV racemic ketamine and were then switched to IN esketamine for maintenance therapy. Patient outcomes were assessed with the Montgomery-Åsberg Depression Rating Scale, Patient Health Questionnaire 9, and Clinical Global Impression of Improvement scale at each visit. Adverse effects were assessed at each treatment. Results indicated that 9 patients either maintained the benefit or showed greater improvement when transitioned to IN esketamine for antidepressant maintenance therapy. One patient had worsening of depression due to an acute psychosocial stressor but still improved from baseline IV racemic ketamine treatment. Six patients returned to work or pursued employment, and 4 patients with suicidal ideation remitted during IV racemic ketamine treatment and had no recurrence of suicidality with IN esketamine. No serious adverse reactions or tolerability issues were observed. This case series reports the outcomes of 10 severely ill patients with TRD who had a clinically meaningful response to IV racemic ketamine and demonstrated a maintenance of effect or continued improvement when transitioned to IN esketamine. Although this finding needs to be replicated in larger, controlled studies, this report provides promising results for patients who have safely and effectively switched to Food and Drug Administration-approved IN esketamine after receiving acute or maintenance depression treatment with off-label IV racemic ketamine.


Salvaging brain ischemia by increasing neuroprotectant uptake via nanoagonist mediated blood brain barrier permeability enhancement.
Ischemic stroke is a leading cause of adult disability and cognitive impairment worldwide. Neuroprotective therapy aims to save neurons by impeding the deleterious ischemic insults. However, the low efficiency of the neuroprotectants crossing blood brain barrier (BBB) prevents their clinical translation. In this work, a nanoagonist (NA) was developed to enhance neuroprotectant uptake by specifically increasing BBB permeability in brain ischemia. This NA first targeted ischemic brain vasculatures, temporarily opened local BBB by activating adenosine 2A receptors, and up-regulated the neuroprotectant uptake in brain ischemia. This NA significantly increased the delivery of superoxide dismutase (SOD), a free radical scavenger, into mouse brain ischemia. The combined treatment of NA/SOD achieved a five-fold ischemic volume reduction rate compared to the animal models treated with SOD alone. Non-invasive magnetic resonance imaging (MRI) confirmed the ischemia targeted BBB opening, increased brain drug delivery efficiency and up-regulated therapeutic response during the combined NA/SOD treatment. Since the inefficient brain drug delivery is a general problem for the treatment of central nervous system (CNS) diseases, this work provides a novel strategy to deliver therapeutics by crossing BBB with high efficiency and targeting specificity.


SUDEP, the aftermath: supporting the bereaved.
Sudden unexpected death in epilepsy is a recurring calamity, yet there is little evidence to guide standards of care for supporting the bereaved. Grief in bereavement includes loss, feelings of guilt, anger and blame. There is also the shock and trauma of the sudden event. How can this be alleviated? This paper focuses on guiding the physician to support the bereaved, while recognising the limited evidence and the varying circumstances that may not always facilitate this. We propose a pathway of care and mode of communication with the deceased's family, with whom contact is currently limited. We suggest timely contact by telephone or in person, followed by ongoing support and referral to voluntary organisations and specialist services, as needed. Clarification and discussion may mitigate inappropriate feelings of guilt and blame, and may help the family with their sudden and unexpected loss.


Amplification of the X-linked Drosophila chorion gene cluster requires a region upstream from the s38 chorion gene.
Genomic sequences controlling follicle cell-specific amplification of the X-linked Drosophila chorion gene cluster were mapped by P element-mediated transformation. Several DNA fragments containing the s38 gene and flanking sequences induced tissue-specific amplification, although replication levels were subject to position effects. Deletion analysis identified a 467-bp region upstream from the s38 transcription start site that contained sequences essential in cis for amplification. The essential region shared 32 bp of imperfect sequence homology with a previously identified region necessary for third chromosome chorion gene cluster amplification. This homologous segment contained a repetitive motif consisting of perfect and imperfect AATAC repeats; it was localized near the boundary of the essential domain since most, but not all, the repeats could be deleted without eliminating transposon-induced amplification. The repetitive region was not required for developmentally regulated s38 transcription, therefore our results identified at least one element required for amplification but not for chorion gene transcription. The homologous repetitive sequences within the amplification-essential regions may constitute part of the replication origins used to differentially replicate the two chorion domains during oogenesis.


Role of Escherichia coli heat shock proteins DnaK and HtpG (C62.5) in response to nutritional deprivation.
Because of the highly conserved pattern of expression of the eucaryotic heat shock genes hsp70 and hsp84 or their cognates during sporulation in Saccharomyces cerevisiae and development in higher organisms, the role of the Escherichia coli homologs dnaK and htpG was examined during the response to starvation. The htpG deletion mutant was found to be similar to its wild-type parent in its ability to survive starvation for essential nutrients and to induce proteins specific to starvation conditions. The dnaK103 mutant, however, was highly susceptible to killing by starvation for carbon and, to a lesser extent, for nitrogen and phosphate. Analysis of proteins induced under starvation conditions on two-dimensional gels showed that the dnaK103 mutant was defective for the synthesis of some proteins induced in wild-type cells by carbon starvation and of some proteins induced under all starvation conditions, including the stationary phase in wild-type cells. In addition, unique proteins were synthesized in the dnaK103 mutant in response to starvation. Although the synthesis of some proteins under glucose starvation control was drastically affected by the dnaK103 mutation, the synthesis of proteins specifically induced by nitrogen starvation was essentially unaffected. Similarly, the dnaK103 mutant was able to grow, utilizing glutamine or arginine as a source of nitrogen, at a rate approximate to that of the wild-type parent, but it inefficiently utilized glycerol or maltose as carbon sources. Several differences between the protein synthetic pattern of the dnaK103 mutant and the wild type were observed after phosphate starvation, but these did not result in a decreased ability to survive phosphate starvation, compared with nitrogen starvation.


Magnetic field evolution in [Formula: see text] collisions at [Formula: see text].
In high energy heavy-ion collisions, the high speed valence charges will produce intense electromagnetic fields within the resulting quark-gluon plasma. Utilizing the AMPT model, this paper presents a comprehensive analysis of the magnetic field distribution generated from non-central collisions between [Formula: see text] nuclei at [Formula: see text]. The initial geometric parameters of the collision and the electric conductivity of the quark-gluon plasma have a dominant influence on the evolution of the magnetic field, while the plasma diffusion and the CME effect have a lesser impact and only slightly involve the original magnetic field by inducing new magnetic fields. This finding suggests that the dynamics of the quark-gluon plasma can be roughly decoupled from the effect of the electromagnetic field.


Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody-drug Conjugate Targeting AXL-expressing Cancers.
AXL, a tyrosine kinase receptor that is overexpressed in many solid and hematologic malignancies, facilitates cancer progression and is associated with poor clinical outcomes. Importantly, drug-induced expression of AXL results in resistance to conventional chemotherapy and targeted therapies. Together with its presence on multiple cell types in the tumor immune microenvironment, these features make it an attractive therapeutic target for AXL-expressing malignancies. ADCT-601 (mipasetamab uzoptirine) is an AXL-targeted antibody-drug conjugate (ADC) comprising a humanized anti-AXL antibody site specifically conjugated using GlycoConnect technology to PL1601, which contains HydraSpace, a Val-Ala cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. This study aimed to validate the ADCT-601 mode of action and evaluate its efficacy in vitro and in vivo, as well as its tolerability and pharmacokinetics. ADCT-601 bound to both soluble and membranous AXL, and was rapidly internalized by AXL-expressing tumor cells, allowing release of PBD dimer, DNA interstrand cross-linking, and subsequent cell killing. In vivo, ADCT-601 had potent and durable antitumor activity in a wide variety of human cancer xenograft mouse models, including patient-derived xenograft models with heterogeneous AXL expression where ADCT-601 antitumor activity was markedly superior to an auristatin-based comparator ADC. Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E-resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo. These preclinical results warrant further evaluation of ADCT-601 in the clinic.


Transcutaneous Auricular Vagus Nerve Stimulation towards Visually Induced Motion Sickness Reduction: A Pilot Study.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel neuromodulation application for vagal afferent stimulation. Owing to its non-invasive nature, taVNS is a potent therapeutic tool for a diverse array of diseases and disorders that ail us. Herein, we investigated taVNS-induced effects on neural activity of participants during visually induced motion sickness. 64-channel electroencephalography (EEG) recordings were obtained from 15 healthy participants in a randomized, within-subjects, cross-over design during sham and taVNS conditions. To assess motion sickness severity, we used the motion sickness assessment questionnaire (MSAQ). We observed that taVNS attenuated theta (4-8 Hz) brain activity in the right frontal, right parietal and occipital cortices when compared to sham condition. The total MSAQ scores, and central, peripheral and sopite MSAQ categorical scores were significantly lower after taVNS compared to sham. These findings reveal for the first time the potential therapeutic role of taVNS toward counter-motion sickness, and suggest that taVNS may be reliable in alleviating symptoms of motion sickness in real-time, non-pharmacologically.Clinical relevance- This suggests taVNS potential to offset motion sickness-induced nausea; which may be of translational value to counter e.g., chemotherapy-induced nausea.


Catabolism of lysosome-related organelles in color-changing spiders supports intracellular turnover of pigments.
Pigment organelles of vertebrates belong to the lysosome-related organelle (LRO) family, of which melanin-producing melanosomes are the prototypes. While their anabolism has been extensively unraveled through the study of melanosomes in skin melanocytes, their catabolism remains poorly known. Here, we tap into the unique ability of crab spiders to reversibly change body coloration to examine the catabolism of their pigment organelles. By combining ultrastructural and metal analyses on high-pressure frozen integuments, we first assess whether pigment organelles of crab spiders belong to the LRO family and second, how their catabolism is intracellularly processed. Using scanning transmission electron microscopy, electron tomography, and nanoscale Synchrotron-based scanning X-ray fluorescence, we show that pigment organelles possess ultrastructural and chemical hallmarks of LROs, including intraluminal vesicles and metal deposits, similar to melanosomes. Monitoring ultrastructural changes during bleaching suggests that the catabolism of pigment organelles involves the degradation and removal of their intraluminal content, possibly through lysosomal mechanisms. In contrast to skin melanosomes, anabolism and catabolism of pigments proceed within the same cell without requiring either cell death or secretion/phagocytosis. Our work hence provides support for the hypothesis that the endolysosomal system is fully functionalized for within-cell turnover of pigments, leading to functional maintenance under adverse conditions and phenotypic plasticity. First formulated for eye melanosomes in the context of human vision, the hypothesis of intracellular turnover of pigments gets unprecedented strong support from pigment organelles of spiders.


[Treatment of hypothyroidism].
Hypothyroidism is a common disease with a prevalence of 5-6% in women and 1-2% in men. Primary hypothyroidism is the most common form (> 98%) autoimmune thyroiditis and thyroid destruction caused by radio-iodine treatment or thyroidectomy are the most common causes. On the basis of relevant literature, an overview of diagnostic criteria and guidelines for treatment is presented. An elevated TSH and a low free thyroxine level are diagnostic for primary hypothyroidism. The presence of anti-TPO antibodies indicates an autoimmune thyroiditis as the cause. In patients with non-thyroidal illness, a range of test abnormalities may be observed, making the interpretation of the test results difficult. Thyroxine is the preferred treatment of hypothyroidism. The therapeutic goal is to achieve a TSH level between 0.5-1.5 mIU/l. Most patients will then have thyroxine values in the upper 1/3 of the reference range, some will have elevated thyroxine values. If necessary, the thyroxine dose can be increased to give a TSH level between 0.2 and 1.0 mIU/l. In patients not satisfactorily treated with thyroxine alone, treatment with thyroxine combined with triiodothyronine may be tried. A diagnosis made on clinical grounds must always be verified biochemically before thyroxine treatment is started. The present literature does not support the treatment of patients complaining of "symptoms of hypothyroidism" such as tiredness, lethargy, weight gain and intolerance to cold, provided that their thyroid function tests are normal.


Anti-inflammatory therapy for COVID-19 infection: the case for colchicine.
The search for effective COVID-19 management strategies continues to evolve. Current understanding of SARS-CoV-2 mechanisms suggests a central role for exaggerated activation of the innate immune system as an important contributor to COVID-19 adverse outcomes. The actions of colchicine, one of the oldest anti-inflammatory therapeutics, target multiple mechanisms associated with COVID-19 excessive inflammation. While many COVID-19 trials have sought to manipulate SARS-CoV-2 or dampen the inflammatory response once patients are hospitalised, few examine therapeutics to prevent the need for hospitalisation. Colchicine is easily administered, generally well tolerated and inexpensive, and holds particular promise to reduce the risk of hospitalisation and mortality due to COVID-19 in the outpatient setting. Successful outpatient treatment of COVID-19 could greatly reduce morbidity, mortality and the demand for rare or expensive care resources (front-line healthcare workers, hospital beds, ventilators, biological therapies), to the benefit of both resource-replete and resource-poor regions.


Quantifying community dynamics of nitrifiers in functionally stable reactors.
A sequential batch reactor (SBR) and a membrane bioreactor (MBR) were inoculated with the same sludge from a municipal wastewater treatment plant, supplemented with ammonium, and operated in parallel for 84 days. It was investigated whether the functional stability of the nitrification process corresponded with a static ammonia-oxidizing bacterial (AOB) community. The SBR provided complete nitrification during nearly the whole experimental run, whereas the MBR showed a buildup of 0 to 2 mg nitrite-N liter(-1) from day 45 until day 84. Based on the denaturing gradient gel electrophoresis profiles, two novel approaches were introduced to characterize and quantify the community dynamics and interspecies abundance ratios: (i) the rate of change [Delta(t)((week))] parameter and (ii) the Pareto-Lorenz curve distribution pattern. During the whole sampling period, it was observed that neither of the reactor types maintained a static microbial community and that the SBR evolved more gradually than the MBR, particularly with respect to AOB (i.e., average weekly community changes of 12.6% +/- 5.2% for the SBR and 24.6% +/- 14.3% for the MBR). Based on the Pareto-Lorenz curves, it was observed that only a small group of AOB species played a numerically dominant role in the nitritation of both reactors, and this was true especially for the MBR. The remaining less dominant species were speculated to constitute a reserve of AOB which can proliferate to replace the dominant species. The value of these parameters in terms of tools to assist the operation of activated-sludge systems is discussed.


Finding the sweet spot: how human fungal pathogens acquire and turn the sugar inositol against their hosts.
Inositol is an essential nutrient with important structural and signaling functions in eukaryotes. Its role in microbial pathogenesis has been reported in fungi, protozoans, and eubacteria. In a recent article, Porollo et al. [mBio 5(6):e01834-14, 2014, doi:10.1128/mBio.01834-14] demonstrated the importance of inositol metabolism in the development and viability of Pneumocystis species--obligate fungal pathogens that remain unculturable in vitro. To understand their obligate nature, the authors used innovative comparative genomic approaches and discovered that Pneumocystis spp. are inositol auxotrophs due to the lack of inositol biosynthetic enzymes and that inositol insufficiency is a contributing factor preventing fungal growth in vitro. This work is in accord with other studies suggesting that inositol plays a conserved role in microbial pathogenesis. Inositol uptake and metabolism therefore may represent novel antimicrobial drug targets. Using comparative genomics to analyze metabolic pathways offers a powerful tool to gain new insights into nutrient utilization in microbes, especially obligate pathogens.


Discordance in postnatal care between mothers and newborns: Measurement artifact or missed opportunity?
Postnatal care (PNC) for mothers and newborns is essential to monitor risks of morbidity and adverse conditions following delivery. Current estimates of the coverage of PNC show substantial discordance between mothers and newborns. We investigate the sources of this discordance in Demographic and Health Surveys (DHS). We used DHS data from 48 countries collected since 2011, spanning phases 6 and 7 of the survey program with 32 and 16 surveys, respectively, analyzed. We assessed the distribution of the reported timing of PNC and conducted a sensitivity analysis that excludes/includes PNC reported within 0-1 hour or PNC in the day 2. Agreement in PNC reporting considered four groups: (1) Concordance, neither mother nor newborn received PNC; (2) Concordance, mother and newborn pair received PNC; (3) Discordance, mother received PNC and newborn did not; of (4) Discordance, mother did not receive PNC but the newborn did. We carried out logistic regressions to understand correlates of PNC discordance. All analyses distinguished phase 6 surveys from phase 7. We found substantial differences in the PNC coverage estimated between phase 6 and phase 7 surveys. The phase 7 PNC questions for newborns were improved to increase the understanding of the questions by respondent which probably led to reducing the large PNC gap between mothers and newborns observed in phase 6 surveys. With phase 6 surveys, PNC coverage for mother was estimated on average at 62% compared to only 31% for newborns. No such gap was observed for phase 7 surveys, where for both mothers and newborns, the PNC coverage estimate was similar, at 56%. For both phases, over half of the reported PNC for mothers and newborns occurred during 0-1 hour following delivery, leading to substantial overestimation of PNC coverage, due to confusion between intrapartum care and PNC. There were 37% discordant cases between mother and newborn, largely in favor of the mother in phase 6 surveys, compared to 16% in phase 7 surveys. In phase 6 surveys, discordant PNC cases were observed largely among facility deliveries vs non-facility deliveries (44% compared to 19%). Current estimates of coverage of PNC from DHS phase 6 surveys appears to include substantial level of measurement noises that could explain substantial part of the mother-newborn discordance in PNC. The PNC estimates appear to capture a substantial number of intrapartum care. Current measurement approaches warrant further validation to ensure accurate monitoring of the PNC programs.


[Introducing research knowledge to nursing students during their initial training: The situation of nursing schools in Lorraine.]
Since 2009, the new nursing training curriculum has included the topic of research in three teaching units in order to introduce it to nursing students. This move has signaled a new era for nurses in France. The development and the durability of research will allow for the marked appearance of a discipline in nursing sciences. Some educators from Lorraine have been carrying out a survey in order to identify the existing means in their nursing schools that can help promote a culture of research right from the beginning of training, through encouraging reading and writing. A mixed methodology has been used and the enquiry has been carried out with a questionnaire addressed to 180 health educators from seventeen nursing schools. The results show a large discrepancy in the schools' resources, but also in the means used to encourage their students to read or write professional or scientific articles. The variety of results seems to be due to the geographical distances between the schools and the universities. The work that the students undertake consists primarily of the professional writings required by the curriculum. Educational approaches to establishing this subject within the schools as well as methodological approaches to reading, writing and their diffusion should therefore be encouraged.


Priming exposures to lipopolysaccharides do not affect the induction of Polycomb target genes upon re-exposure.
The Polycomb group (PcG) proteins are chromatin factors underlying the process of transcriptional memory to preserve developmental decisions and keep cellular identities. However, not only developmental signals need to be memorized and thus maintained during the life of an organism. For host protection against pathogens, also a memory of previous exposures to an immunogenic stimulus is crucial to mount a more protective immune response upon re-exposure. The antigen-specific adaptive immunity in vertebrates is an example of such a memory to previous immunogenic stimulation. Recently, adaptive characteristics were also attributed to innate immunity, which was classically seen to lack memory. However, the mechanistic details of an adaptive innate immune response are yet to be fully understood and chromatin-based epigenetic mechanisms seem to play an important role in this phenomenon. Possibly, PcG proteins can contribute to such an epigenetic innate immune memory. In this study, we analyzed whether the PcG system can mediate a transcriptional memory of exposure to lipopolysaccharides (LPS). To this end, various forms of LPS pre-treatment were applied to reporter cells and expression kinetics of PcG target genes were analyzed after a second LPS exposure. Neither single nor multiple LPS pre-treatment affected the induction of endogenous LPS-responsive transcripts upon re-exposure. Altogether, our extensive analyses did not provide any evidence for a PcG system-mediated memory of LPS stimulation.


[Primary structure of cDNA for bovine beta-casein].
In this work the complete sequence of 1097 nucleotide bovine beta-casein cDNA has been determined. Sequencing of end labeled fragments was performed using the method of Maxam and Gilbert. Bovine beta-casein cDNA consist of a 672 nucleotide coding region, flanked by 60 nucleotide 5' and 358 nucleotide 3'-noncoding region. The restriction map of beta-casein cDNA was constructed. The computer analysis was done and the comparisons of the complete sequence of bovine beta-casein cDNA with other sequences, coding caseins in bovine, rat and guinea-pig was performed. It was determined, that cloned cDNA is related to genetic variant A1.


Microsurgical roto-extractor instrument for vitrectomy.
A double-edged cutting blade oscillates between a clockwise and a counter-clockwise high speed rotation without completing a full revolution. This imparts a great mechanicaldvantage and safety to the instrument's cutting efficiency. The cutter may also be used with a continuous high speed clockwise rotation. Multiple interchangeable probe tips are used that are of either double- or triple-walled construction. A fiber-optic light pipe surrounds the probe tip used for deep vitrectomy in conjunction with an irrigated fundus lens. A film will illustrate the use of the roto-extractor in two diabetic patients with old unabsorbed vitreous hemorrhage and membranes. In the first case, a pars plana incision was used for vitrectomy in conjunction with a cataract extraction. In the second case, the para plana vitrectomy was combined with an optical iridectomy necessitated by the presence of an updrawn pupil following previous cataract extraction complicated by vitreous loss. To date, 12 roto-extractors have been distributed to 12 various teaching institutions throughout the United States.


Comparison of Macular Pigment Optical Density in Glaucoma Patients and Healthy Subjects - A Prospective Diagnostic Study.
To evaluate the relationship between macular pigment optical density (MPOD) and glaucoma. Forty-three patients with an established glaucoma diagnosis (25 females, 18 males, mean age 70 (range 34-84)) and 43 healthy controls (28 females, 15 males, mean age 62 (range 30-87)) were included in this prospective diagnostic case-control study. All subjects underwent detailed eye examination including ophthalmoscopy, best-corrected visual acuity, biomicroscopy, measurement of the axial length of the eye, objective refraction, lens status, central foveal thickness on spectral-domain optical coherence tomography (SD-OCT). In all glaucoma patients, a visual field assessment and a measurement of the retinal nerve fibre layer (RNFL) on SD-OCT were done. MPOD was determined using the macula pigment module of the Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) at 0.51°, 1.02° and 1.99° retinal eccentricity using two-wavelength autofluorescence imaging. In the glaucoma group, the median of the visual field mean defect was 5.1 db (quartiles 3.0 and 13.5) and the mean RNFL-thickness global was 65.9 µm (SD ± 16.1). Median MPOD measured at 0.51°, 1.02° and 1.99° retinal eccentricity in the glaucoma group was 0.42 DU, 0.34 DU and 0.13 DU, in the control group 0.40 DU, 0.35 DU and 0.12 DU respectively. There was no statistically significant difference of median MPOD between glaucomatous and control eyes (p=0.510, 0.735, 0.481). No significant relation between MPOD at 1.02 retinal eccentricity and the presence of glare symptoms was found (p=0.948). However, age seems to correlate with median MPOD measured at 1.02 retinal eccentricity (p=0.017). There was no evidence for lower MPOD levels in our glaucoma patients; lower MPOD was not related to the presence of glare symptoms. However there seems to be a positive correlation between age and MPOD at 1.02° retinal eccentricity. To further investigate the relation between glare reported by glaucoma patients and glare disability linked to lower MPOD levels, additional studies are necessary that include both detailed inquiry of the quality of glare and a glare quantification and precise analysis of MPOD levels in glaucoma patients.


Effects of acute and chronic flunitrazepam on delay discounting in pigeons.
Delay to delivery of a reinforcer can decrease responding for that reinforcer and increase responding for smaller reinforcers that are available concurrently and delivered without delay; acute administration of drugs can alter responding for large, delayed reinforcers, although the impact of chronic treatment on delay discounting is not well understood. In this experiment, the effects of repeated administration of the benzodiazepine flunitrazepam were studied in 6 pigeons responding on one key to receive food that was delivered immediately and on a second key to receive a larger amount of food that was delivered following delays which increased across a single session. Pigeons responded predominantly for the large reinforcer when there were no delays and when delays were short; however, as delays increased, responding for the large reinforcer decreased. Acutely, flunitrazepam (0.32, 1.0 and 3.2 mg/kg) dose-dependently increased responding for the large reinforcer, shifting the discounting curve rightward and upward. Repeated administration of flunitrazepam (0.32, 1.0 and 3.2 mg/kg, each for six sessions, separated by one session during which vehicle was administered) did not markedly alter its effects on responding for the large reinforcer, indicating that the development of tolerance to this effect of flunitrazepam is modest under these conditions.


[Quality profile of a CAM rehabilitation clinic--Part 1: Structure, quality assurance and interventions].
To present a patient care evaluation program exemplified by a rehabilitation clinic for complementary and alternative medicine (CAM) with focus on aspects of structure quality, steps of quality assurance and interventions administered. Assessment of previously defined criteria of structure (general characteristics of the facility, staff, medical equipment and constructional features, medical concept, continuing care, internal communication) and measures of quality assurance with the aid of a questionnaire filled in by the management of the hospital. Development of internal guidelines for diagnostics and therapy with respect to relevant diseases. The clinic's structure profile describes the indications and contraindications in effect, the quantity and qualification structure of staff, and the constructional and medical equipment details. Based on a multidimensional bio-psycho-social concept the general objectives of rehabilitation are derived. According to the medical concept the corresponding diagnostic and therapeutic methods are presented. Guidelines for treatment were exemplified by patients with migraine. The structural features do not fully meet the preconditions valid for the various indications in rehabilitation. As CAM hospitals define themselves by the methods of intervention they apply rather than by the indications to be treated they demand for an exceptional position.


The effects of multiple metal contamination on ectomycorrhizal Scots pine (Pinus sylvestris) seedlings.
Experiments were conducted to investigate the effects of single and multiple metal contamination (Cd, Pb, Zn, Sb, Cu) on Scots pine seedlings colonised by ectomycorrhizal (ECM) fungi from natural soil inoculum. Seedlings were grown in either contaminated field soil from the site of a chemical accident, soils amended with five metals contaminating the site, or in soil from an uncontaminated control site. Although contaminated and metal-amended soil significantly inhibited root and shoot growth of the Scots pine seedlings, total root tip density was not affected. Of the five metals tested in amended soils, Cd was the most toxic to ECM Scots pine. Field-contaminated soil had a toxic effect on ECM fungi associated with Scots pine seedlings and caused shifts in ECM species composition on ECM seedlings. When compared to soils amended with only one metal, soils amended with a combination of all five metals tested had lower relative toxicity and less accumulation of Pb, Zn and Sb into seedlings. This would indicate that the toxicity of multiple metal contamination cannot be predicted from the individual toxicity of the metals investigated.


The association between daytime attendance and out-of-hours frequent attendance among adult patients in general practice.
Frequent attenders (FAs) account for a large proportion of daytime consultations in general practice. However, no studies have so far been conducted to establish whether daytime FAs are also out-of-hours FAs. To analyse the association between daytime attendance and out-of-hours frequent attendance. A registry-based study of individual face-to-face contacts with general practice during daytime and out of hours, based on National Health Insurance files. General practices in Aarhus County, Denmark (630,000 inhabitants). A total of 416,172 adults, i.e. all adults registered with a general practice during a 12-month period from November 1997 to October 1998 were included. Odds ratios (OR) for frequent attendance out of hours were stratified for age, sex, and frequency of contacts during daytime were calculated. A strong association was observed between daytime level of attendance and out-of-hours level of attendance (OR = 2.9-6.3 among patients with low daytime attendance, OR = 33.7-99.8 among daytime FAs). Daytime FAs accounted for one-third of the daytime contacts, one-third of the out-of-hours contacts, and 42% of out-of-hours FAs. More than half of the daytime FAs did not attend out of hours. Two per cent of the out-of-hours FAs had no contacts during the daytime. Frequent attendance in daytime was very strongly associated with frequent attendance out of hours, and daytime FAs accounted for a large proportion of all contacts with general practice.


Analysis of Acrolein-Derived 1, N2-Propanodeoxyguanosine Adducts in Human Lung DNA from Smokers and Nonsmokers.
Acrolein, the simplest α,β-unsaturated aldehyde, is present in relatively large quantities in cigarette smoke, and several studies have raised the possibility of it being a major etiological agent for smoking-related lung cancer. Acrolein reacts directly with DNA to form primarily Acr-dGuo adducts, which serve as important biomarkers for the assessment of exposure to acrolein and its potential role in smoking-related lung cancer. In this study, we developed an ultrasensitive and low-artifact method using liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry to quantitate Acr-dGuo adducts in normal lung tissue DNA obtained at surgery from lung cancer patients who never smoked and from those who continued smoking until surgery, as confirmed by urinary total cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol. This provides a direct comparison of Acr-dGuo levels in human lung tissue as a result of cigarette smoking versus other etiological causes. There was no significant difference between the total Acr-dGuo levels in smokers (28.5 ± 14.9 adducts/109 nucleotides) and nonsmokers (25.0 ± 10.7 adducts/109 nucleotides), suggesting rapid removal of acrolein by glutathione conjugation and other detoxification mechanisms. Our results do not support the hypothesis that acrolein is a major etiological agent for cigarette smoking-related DNA damage.


Baroreflex sensitivity and power spectral analysis in different extrapyramidal syndromes.
Cardiac autonomic abnormalities have been described in Parkinson's disease and other extrapyramidal syndromes. To investigate baroreflex sensitivity as an important risk marker of cardiovascular mortality in patients with Parkinson's disease and other extrapyramidal syndromes. We recorded continuously blood pressure, ECG and respiration in 35 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 46 patients with idiopathic Parkinson's disease (PD) and in 27 corresponding healthy subjects (Con). Recordings of 2 min at rest were used to calculate baroreflex and spectral analysis of heart rate and systolic blood pressure. Resting baroreflex sensitivity (BRS) was significantly lower in the MSA and the PSP group but not in the PD group in comparison to the Con group. With increasing Hoehn & Yahr stage, BRS significantly decreased in all patient groups. In spectral analysis, all patient groups had a significantly lower relative low frequency (LF)-band power than the healthy controls. Patients with extrapyramidal disorders frequently demonstrate pathologically decreased BRS values and abnormalities of spectral analysis. This may have fundamental impact on the cardiovascular prognosis of patients with extrapyramidal disease.


A smile is all you need: predicting limiting activity coefficients from SMILES with natural language processing.
The knowledge of mixtures' phase equilibria is crucial in nature and technical chemistry. Phase equilibria calculations of mixtures require activity coefficients. However, experimental data on activity coefficients are often limited due to the high cost of experiments. For an accurate and efficient prediction of activity coefficients, machine learning approaches have been recently developed. However, current machine learning approaches still extrapolate poorly for activity coefficients of unknown molecules. In this work, we introduce a SMILES-to-properties-transformer (SPT), a natural language processing network, to predict binary limiting activity coefficients from SMILES codes. To overcome the limitations of available experimental data, we initially train our network on a large dataset of synthetic data sampled from COSMO-RS (10 million data points) and then fine-tune the model on experimental data (20 870 data points). This training strategy enables the SPT to accurately predict limiting activity coefficients even for unknown molecules, cutting the mean prediction error in half compared to state-of-the-art models for activity coefficient predictions such as COSMO-RS and UNIFACDortmund, and improving on recent machine learning approaches.


Nocardiopsis compostus sp. nov., from the atmosphere of a composting facility.
Three strains (KS8, KS9T and KS21), isolated from air samples near a composting facility, were subjected to taxonomic analyses (characterized using a polyphasic approach). Morphological and chemotaxonomic characteristics of the isolates were in agreement with those described for members of the genus Nocardiopsis. On the basis of 16S rRNA sequence comparison and phenotypic tests, KS21 clearly belonged to Nocardiopsis alba. KS8 and KS9T showed less than 98% 16S rRNA gene sequence similarity to any of the previously described Nocardiopsis species. The polar lipid profiles of both isolates consisted of four major compounds, phosphatidylmonomethylethanolamine, phosphatidylcholine, diphosphatidylglycerol and phosphatidylglycerol, in addition to two unknown phospholipids. The major menaquinones in KS8 and KS9T were MK-10(H8), MK-11(H8), MK-10(H6) and MK-12. Furthermore, MK-13, MK-11(H6), MK-9(H8) and MK-10(H4) could be detected in significant amounts. The fatty acid composition included iso- and anteiso-branched acids combined with tuberculostearic acid (Me18:0), straight-chain saturated (16:0, 18:0) and unsaturated (16:1, 17:1, 18:1) fatty acids. On the basis of these results, KS8 and KS9T clearly represent a novel species of the genus Nocardiopsis, for which the name Nocardiopsis compostus sp. nov. is proposed (type strain KS9T = DSM 44551T= NRRL B-24145T).


Clinical efficacy of acupuncture combined with Chinese herbal medication for recurrent implantation failure infertility of kidney deficiency and blood stasis and its effects on serum p38MAPK and JAK/STAT protein expression.
To observe the effects of acupuncture combined with Chinese herbal medication on pregnancy outcomes in patients with recurrent implantation failure (RIF) infertility of kidney deficiency and blood stasis, and to explore its effects on the protein expression of serum p38MAPK and JAK/STAT. Sixty-two patients with RIF infertility of kidney deficiency and blood stasis who were scheduled for artificial cycle frozen-thawed embryo transfer were randomly divided into an observation group (31 cases, 4 cases dropped out) and a control group (31 cases, 3 cases were eliminated). The patients in the control group were treated with conventional artificial cycle frozen-thawed embryo transfer. On the basis of the control group, the patients in the observation group were treated with acupuncture combined with Chinese herbal medication. Acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4) and bilateral Neiguan (PC 6), Zigong (EX-CA 1), Guilai (ST 29), Zusanli (ST 36), Taichong (LR 3), Shenshu (BL 23), Ciliao (BL 32), with each session lasting for 30 minutes, once every other day. Chinese herbal medication was administered to Bushen Huoxue (tonifing the kidney and activating blood circulation) decoction, with one dose per day, starting from the 3rd to 5th day of the menstrual cycle and continuing until 1 day before embryo transfer. Clinical pregnancy rate, embryo implantation rate, live birth rate, and biochemical pregnancy rate were compared between the two groups. TCM symptom score, platelet count (PLT), and plasma D-dimer level were assessed before treatment and 1 day before embryo transfer. Western blot method was used to detect the expression of serum P38MAPK, JAK, and STAT proteins before treatment and 1 day before embryo transfer. In the observation group, the clinical pregnancy rate, embryo implantation rate, and live birth rate were higher (P<0.05), while the biochemical pregnancy rate was lower (P<0.05) than those in the control group. One day before embryo transfer, both groups showed a decrease in TCM symptom scores, PLT, and plasma D-dimer levels compared to those before treatment (P<0.05), and the observation group had lower TCM symptom scores and plasma D-dimer levels than the control group (P<0.05). One day before embryo transfer, the expression levels of serum p38MAPK, JAK, and STAT proteins in both groups were lower than those before treatment (P<0.05), and the observation group had lower serum p38MAPK protein expression than the control group (P<0.05). Acupuncture combined with Chinese herbal medication can improve the clinical pregnancy rate, embryo implantation rate, live birth rate, and reduce the biochemical pregnancy rate in RIF infertility patients of kidney deficiency and blood stasis. Its mechanism of action may be related to down-regulating plasma D-dimer level and protein expression of serum p38MAPK.


Structure and expression of two temperature-specific surface proteins in the ciliated protozoan Tetrahymena thermophila.
The presence of specific proteins (known as immobilization antigens) on the surface of the ciliated protozoan Tetrahymena thermophila is under environmental regulation. There are five different classes (serotypes) of surface proteins which appear on the cell surface when T. thermophila is cultured under different conditions of temperature or incubation medium; three of these are temperature dependent. The appearance of these proteins on the cell surface is mutually exclusive. We used polyclonal antibodies raised against 30 degrees C (designated SerH3)- and 40 degrees C (designated SerT)-specific surface antigens to study their structure and expression. We showed that these surface proteins contain at least one disulfide bridge. On sodium dodecyl sulfate-denaturing polyacrylamide gels, the nonreduced 30 degrees C- and 40 degrees C-specific surface proteins migrated with molecular sizes of 69 and 36 kilodaltons, respectively. The reduced forms of the proteins migrated with molecular sizes of 58 and 30 kilodaltons, respectively. The synthesis of the surface proteins responded rapidly and with a time course similar to that of the incubation temperature. The synthesis of each surface protein was greatly reduced within 1 h and undetectable by 2 h after a shift to the temperature at which the protein is not expressed. Surface protein synthesis resumed by the end of 1 h after a shift to the temperature at which the protein is expressed. The temperature-dependent induction of these surface proteins appears to be dependent on the synthesis of new mRNA, as indicated by a sensitivity to actinomycin D. Surface protein syntheses were mutually exclusive except at a transition temperature. At 35 degrees C both surface proteins were synthesized by a cell population. These data support the potential of this system as a model for the study of the effects of environmental factors on the genetic regulation of cell surface proteins.


Comment on "Dynamic shifts of limited working memory resources in human vision".
Bays and Husain (Reports, 8 August 2008, p. 851) reported that human working memory, the limited information currently in mind, reflects resources distributed across all items in an array. In an alternative interpretation, memory is limited to several well-represented items. We argue that this item-limit model fits the extant data better than the distributed-resources model and is more interpretable theoretically.


Mantel-Haenszel test statistics for correlated binary data.
This paper proposes two new Mantel-Haenszel test statistics for correlated binary data in 2 x 2 tables that are asymptotically valid in both sparse data (many strata) and large-strata limiting models. Monte Carlo experiments show that the statistics compare favorably to previously proposed test statistics, especially for 5-25 small to moderate-sized strata. Confidence intervals are also obtained and compared to those from the test of Liang (1985, Biometrika 72, 678-682).


Sonographic Guidance for Supraclavicular Brachial Plexus Blocks: Single vs. Double Injection Cluster Approach.
The cluster approach for supraclavicular brachial plexus block (SC-BPB) can be easily performed but may result in asymmetric local anesthetic (LA) spread. The authors hypothesized that the use of a cluster approach in each of the 2 planes would achieve better 3-dimensional LA distribution than the traditional single cluster approach. The purpose of the present study was to compare a double injection (DI) in 2 planes (one injection in each plane) with the traditional single injection (SI) cluster approach for ultrasound-guided SC-BPB. A randomized, controlled trial. Department of Anesthesiology and Pain Medicine, Gachon University Gil Medical Center. In the SI group (n = 18), 30 mL of LA was injected into the main neural cluster after penetrating the brachial plexus sheath laterally. In the DI group (n = 18), the needle penetrated the sheath in a downward direction at the first skin puncture, and 15 mL of LA was injected, and at the second skin puncture (behind the initial puncture site), the needle penetrated the sheath in an upward direction, and 15 mL was again injected. Ultrasound-guided SC-BPB was evaluated from immediately after the block every 5 minutes to 30 minutes by sensory and motor testing. The main outcome variables were procedural time; onset time (time for complete sensory and motor block of the median, radial, ulnar, and musculocutaneous nerves); and rate of blockage of all 4 nerves. Procedure times (medians [interquartile range]) were similar in the DI and SI groups (5.5 [4.75 - 8] vs. 5 [4 - 7] minutes, respectively; P = 0.137). Block onset time in the DI group was not significantly different from that in the SI group (10 [5 - 17.5] vs. 20 [6.25 - 30] minutes, P = 0.142). However, the rate of blockage of all 4 nerves was significantly higher in the DI group (94% vs. 67%, P = 0.035). Although the results of this study indicate LA distribution in the DI group was more evenly spread within brachial plexus sheaths than in the SI group, this was not confirmed by ultrasonography or contrast radiography. The DI approach can be performed easily as single cluster approach and increases the consistency of ultrasound-guided SC-BPB over the SI approach in terms of the rate of blocking of all 4 nerves. Key words: Brachial plexus block, corner pocket approach, cluster approach, multiple injection, supraclavicular block, ultrasound.


TRPV1 and TRPV4 play pivotal roles in delayed onset muscle soreness.
Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes tenderness and movement related pain after some delay (delayed-onset muscle soreness, DOMS). We previously demonstrated that nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are up-regulated in exercised muscle through up-regulation of cyclooxygenase (COX)-2, and they sensitized nociceptors resulting in mechanical hyperalgesia. There is also a study showing that transient receptor potential (TRP) ion channels are involved in DOMS. Here we examined whether and how TRPV1 and/or TRPV4 are involved in DOMS. We firstly evaluated a method to measure the mechanical withdrawal threshold of the deep tissues in wild-type (WT) mice with a modified Randall-Selitto apparatus. WT, TRPV1-/- and TRPV4-/- mice were then subjected to LC. Another group of mice received injection of murine NGF-2.5S or GDNF to the lateral gastrocnemius (LGC) muscle. Before and after these treatments the mechanical withdrawal threshold of LGC was evaluated. The change in expression of NGF, GDNF and COX-2 mRNA in the muscle was examined using real-time RT-PCR. In WT mice, mechanical hyperalgesia was observed 6-24 h after LC and 1-24 h after NGF and GDNF injection. LC induced mechanical hyperalgesia neither in TRPV1-/- nor in TRPV4-/- mice. NGF injection induced mechanical hyperalgesia in WT and TRPV4-/- mice but not in TRPV1-/- mice. GDNF injection induced mechanical hyperalgesia in WT but neither in TRPV1-/- nor in TRPV4-/- mice. Expression of NGF and COX-2 mRNA was significantly increased 3 h after LC in all genotypes. However, GDNF mRNA did not increase in TRPV4-/- mice. These results suggest that TRPV1 contributes to DOMS downstream (possibly at nociceptors) of NGF and GDNF, while TRPV4 is located downstream of GDNF and possibly also in the process of GDNF up-regulation.


Is the psoas a hip flexor in the active straight leg raise?
Psoas function is a topic of considerable relevance in sports and clinical science. However, the literature on psoas function is not sufficiently consistent. Questions are, amongst others, if during hip flexion the psoas always has the same function as the iliacus, and if the psoas affects the hip more than the lumbar spine. In the present study, 17 healthy women, 20-40 years, performed the active straight leg raise (ASLR), with the right or the left leg ("Side"), and without or with weight added above the ankle ("Condition"). Electromyographic (EMG) activity of psoas and iliacus were recorded with fine-wire electrodes, and of rectus femoris and adductor longus with surface electrodes, all on the right side. Movements of the leg were recorded with active markers and a camera system. During ASLR, the iliacus, rectus femoris, adductor longus and psoas were active ipsilaterally, but psoas was also active contralaterally. All muscles started to contract before movement onset, the iliacus, rectus femoris, and adductor longus largely at the same time, before the psoas. There was no significant difference between the amplitude or time of onset of ipsilateral and contralateral psoas EMG activity, nor was there a significant interaction between Side and Condition for the psoas. Although ipsilateral psoas activity is consistent with the psoas being a hip flexor, contralateral activity is not. The most simplest explanation of the pattern found is that the psoas is bilaterally recruited to stabilize the lumbar spine, probably in the frontal plane.


Salicylic acid and its function in plant immunity.
The small phenolic compound salicylic acid (SA) plays an important regulatory role in multiple physiological processes including plant immune response. Significant progress has been made during the past two decades in understanding the SA-mediated defense signaling network. Characterization of a number of genes functioning in SA biosynthesis, conjugation, accumulation, signaling, and crosstalk with other hormones such as jasmonic acid, ethylene, abscisic acid, auxin, gibberellic acid, cytokinin, brassinosteroid, and peptide hormones has sketched the finely tuned immune response network. Full understanding of the mechanism of plant immunity will need to take advantage of fast developing genomics tools and bioinformatics techniques. However, elucidating genetic components involved in these pathways by conventional genetics, biochemistry, and molecular biology approaches will continue to be a major task of the community. High-throughput method for SA quantification holds the potential for isolating additional mutants related to SA-mediated defense signaling.


Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting.
The need to control chemotherapy-induced nausea and vomiting is continuously stimulating research to find better options for the optimal antiemetic care. Palonosetron is different from conventional serotonin receptor antagonists not only by the fact of having a longer half-life but also by higher binding affinity for serotonin receptors. It is the first agent in the class which is approved for preventing both delayed and acute emesis induced by moderately emetogenic chemotherapy. Recent studies using palonosetron-based antiemetic regimens, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Palonosetron plus dexamethasone given as a pre-treatment infusion was effective for preventing acute and delayed emesis after moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone and aprepitant was highly effective in preventing emesis in the days following administration of moderately emetogenic chemotherapy. Treatment was well tolerated, with no unexpected adverse events. Multiple-day dosing of palonosetron plus dexamethasone was safe and effective for prevention of emesis induced by 5-day cisplatin-based chemotherapy. There was no evidence of cumulative toxicity when palonosetron was given three times over 5 days. Further evidence from ongoing clinical trials with palonosetron with or without dexamethasone will be available soon. Palonosetron represents an useful addition to the therapeutic armamentarium for the management of chemotherapy-induced nausea and vomiting. Further studies are needed to assess the effectiveness of palonosetron in combination with dexamethasone compared with that of older serotonin receptor antagonists combined with dexamethasone. However, palonosetron may offer advantages of convenience over the short-acting older antagonists due to its ability to be given as a single intravenous dose prior to chemotherapy.


The farm family perception of occupational health: a multistate survey of knowledge, attitudes, behaviors, and ideas.
It is vitally important to integrate the views and concerns of the farm family into the process of policy development. If the input is not there, policy planners could implement programs that are philosophically separated from the farm families' concerns and attitudes. This would destroy credibility and future farmer support of any new program development. From May of 1988 to April of 1989, a phone and mail survey of approximately 1,500 farmers and spouses was conducted to assess knowledge, attitudes, and behaviors regarding agricultural safety and health. The survey was conducted in Iowa, New York, South Carolina, and Washington state. Preliminary results from Iowa and New York indicated that: 1) farmers value highly, and are concerned with, occupational health and safety issues; 2) farmers report that their major concerns include stress, trauma and respiratory problems; 3) farmers would like access to an occupational health and safety service; and 4) any new farm health and safety programs must include farmer input to ensure practicality, applicability, and acceptance.


Blood culture use in the emergency department in patients hospitalized with respiratory symptoms due to a nonpneumonia illness.
Guidelines and performance measures recommend obtaining blood cultures in selected patients hospitalized with community-acquired pneumonia (CAP). Due to inherent diagnostic uncertainty, there may be spillover effects of these recommendations on other conditions that resemble pneumonia. Using data from the 2002 to 2010 National Hospital Ambulatory Medical Care Survey, a nationally representative sample of emergency department (ED) visits in the United States, we analyzed trends in obtaining cultures in patients hospitalized with respiratory symptoms due to a nonpneumonia illness using linear regression. The most common primary admission diagnoses for these visits included heart failure (16%), chronic obstructive pulmonary disease (13%), and chest pain (12%). The proportion of cultures collected in the ED during these visits increased from 10% (95% confidence interval [CI]: 7%-14%) in 2002 to 20% (95% CI: 16%-26%) in 2010 (P<0.001 for the trend). This represented a parallel increase compared to patients hospitalized with CAP (P=0.12 for the difference in trends). The increase in collecting cultures in the ED in patients hospitalized with respiratory symptoms due to a nonpneumonia illness suggests an important potential unintended consequence of blood culture recommendations for CAP. More attention to the judicious use of blood cultures to reduce harm and costs is needed.


Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health.
Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.


Seminal plasma protein networks and enriched functions in varicocele: Effect of smoking.
To verify a possible synergistic effect of smoking and varicocele on the seminal plasma proteome and biological functions, a cross-sectional study was performed in 25 smokers and 24 nonsmokers. Samples were used for conventional semen analysis, functional analysis (DNA fragmentation, acrosome integrity and mitochondrial activity) and proteomics by a shotgun approach. Functional enrichment of biological pathways was performed in differentially expressed proteins. Smokers presented lower ejaculate volume (p = .027), percentage of progressively motile spermatozoa (p = .002), total sperm count (p = .039), morphology (p = .001) and higher percentage of immotile spermatozoa (p = .03), round cell (p = .045) and neutrophil count (p = .009). Smokers also presented lower mitochondrial activity and acrosome integrity and higher DNA fragmentation. We identified and quantified 421 proteins in seminal plasma, of which one was exclusive, 21 were overexpressed and 70 were underexpressed in the seminal plasma of smokers. The proteins neprilysin, beta-defensin 106A and histone H4A were capable of predicting the smoker group. Enriched functions were related to immune function and sperm machinery in testis/epididymis. Based on our findings, we can conclude that cigarette smoking leads to the establishment of inflammatory protein pathways in the testis/epididymis in the presence of varicocele that seems to act in synergy with the toxic components of the cigarette.


Educational outreach visits: effects on professional practice and health care outcomes.
Outreach visits have been identified as an intervention that may improve the practice of health care professionals, in particular prescribing. This type of 'face to face' visit has been referred to as university-based educational detailing, public interest detailing, and academic detailing. To assess the effects of outreach visits on improving health professional practice or patient outcomes. We searched MEDLINE up to March 1997, the Research and Development Resource Base in Continuing Medical Education, and reference lists of related systematic reviews and articles. Randomised trials of outreach visits (defined as a personal visit by a trained person to a health care provider in his or her own setting). The participants were health care professionals. Two reviewers independently extracted data and assessed study quality. Eighteen studies were included involving more than 1896 physicians. All of the outreach visit interventions consisted of several components, including written materials and conferences. Reminders or audit and feedback complemented some visits. In 13 studies, the targeted behaviours were prescribing practices. In three studies, the behaviours were preventive services, including counselling for smoking cessation. In two studies, the outreach visits were directed toward improving the general management of common problems encountered in general practice, including asthma, diabetes, otitis media, hypertension, anxiety, and acute bronchitis. All studies examined physician behaviour and in three studies other health professionals such as nurses, nursing home attendants or health care workers were targeted. Positive effects on practice were observed in all studies. Only one study measured a patient outcome. Few studies examined the cost effectiveness of outreach. Educational outreach visits, particularly when combined with social marketing, appear to be a promising approach to modifying health professional behaviour, especially prescribing. Further research is needed to assess the effects of outreach visits for other aspects of practice and to identify key characteristics of outreach visits that are important to its success. The cost-effectiveness of outreach visits is not well evaluated.


Clinical use and material wear of polymeric tracheostomy tubes.
The objectives were to compare the duration of use of polymeric tracheostomy tubes, i.e., silicone (Si), polyvinyl chloride (PVC), and polyurethane (PU), and to determine whether surface changes in the materials could be observed after 30 days of patient use. Data were collected from patient and technical records for all tracheostomized patients attending the National Respiratory Center in Sweden. In the surface study, 19 patients with long-term tracheostomy were included: six with Bivona TTS Si tubes, eight with Shiley PVC tubes, and five with Trachoe Twist PU tubes. All tubes were exposed in the trachea for 30 days before being analyzed by scanning electron microscopy (SEM) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). New tubes and tubes exposed in phosphate-buffered saline were used as reference. Si tubes are used for longer periods of time than those made of PVC (P<.0001) and PU (P=.021). In general, all polymeric tubes were used longer than the recommended 30-day period. Eighteen of the 19 tubes exposed in patients demonstrated, in one or more areas of the tube, evident surface changes. The morphologic changes identified by SEM correlate well with the results obtained by ATR-FTIR. Si tracheostomy tubes are in general used longer than those made of PVC and PU. Most of the tubes exposed in the trachea for 30 days suffered evident surface changes, with degradation of the polymeric chains as a result.