Determinants of Knowledge and Attitudes Regarding Pain among Nurses in a University Hospital: A Cross-sectional Study.
The aim of this cross-sectional study was to evaluate the primary determinants of knowledge and attitudes regarding pain among nurses in a hospital setting. All registered nurses employed at participating units at a university hospital were invited to participate. Information on work experience, education, and hospital unit was evaluated using a questionnaire. The Knowledge and Attitude Survey Regarding Pain instrument was used to assess knowledge on pain management. The difference in knowledge between nurses with different levels of education was assessed with analysis of variance. The discriminatory ability of each question was determined with item response theory, and the association between correct answers to individual items and the total score were calculated using linear regression. Participants were 235 nurses, 51% of the 459 invited. The overall pain knowledge score was 26.1 (standard deviation 5.3, range 8-38) out of a total of 40 possible. Those with an advanced degree in nursing scored on average 2.9 points higher than those who did not have an advance degree (95% confidence interval: 0.9-4.7). Responses to clinical vignette questions showed more difference between nurses with different levels of knowledge of pain management than the other questions. Participants with the correct response to the best discriminatory item had 5.35 (95% confidence interval 4.08-6.61) points higher total score than those with an incorrect answer. Higher education is associated with better knowledge on pain management. To assess pain knowledge, the ability to interpret and solve a clinical vignette leads to better results than answering direct questions.


Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population.
Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.


A perspective on enzyme catalysis.
The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion. Such coupled networks have important implications for the origin and evolution of enzymes, as well as for protein engineering.


Insights into Macrophage Heterogeneity and Cytokine-Induced Neuroinflammation in Major Depressive Disorder.
Over 350 million individuals suffer from depression, a psychiatric illness classified as major depressive disorder (MDD) with symptoms that include a loss of interest or pleasure in life accompanied by depressed mood. The present understanding of major depressive disorder does not encompass a systematic characterization of the neurobiological processes that drive the behavioral physiology in patients diagnosed with major depressive disorder. Psychiatric illness is a complex intersection between genetics, physiology, immunology and environmental stress. The increased attention to the relevance of depression has led to new discoveries that highlight the biological significance of 'neuroinflammation' and immunity underlying a spectrum of psychiatric illnesses. The process of neuroinflammation involves sentinel immune cells in the central nervous system (CNS). The activation and polarization of microglia, CNS-resident macrophages, modulates the production and secretion of pro-inflammatory cytokines implicated in the etiology of major depressive disorder, and this phenomenon has been aptly titled the 'macrophage theory of depression'. Of particular interest are three hallmark cytokines, IL-6, TNFα and IL-1β, which have been studied extensively in basic research, cell-receptor signaling and drug development. The field of inflammasome-mediated neuroinflammation is an emerging area of MDD research that is providing new cellular insight into how macrophages mechanistically support cytokine-associated neuropathology, particularly in the case of IL-1β-associated inflammation in MDD. With the increasing number of individuals identified with depression, a comprehensive understanding of macrophage-cytokine signaling pathways in the CNS in depression is necessary for developing effective anti-depressant therapeutics.


'Hurrah for the missing link!': a history of apes, ancestors and a crucial piece of evidence.
In the nineteenth century the idea of a 'missing link' connecting humans with the rest of the animal kingdom was eagerly embraced by professional scientists and popularizers. After the publication of Charles Darwin's Origin of Species in 1859, many tied the idea and subsequent search for a crucial piece of evidence to Darwin and his formulation of the theory of evolution by natural selection. This article demonstrates that the expression was widely used and that the framework for discussions about human's relation to the apes and gaps in the fossil record were well in place and widely debated long before Origin of Species became the standard reference for discussing human evolution. In the second half of the century the missing link gradually became the ultimate prize in palaeoanthropology and grew into one of the most powerful, celebrated and criticized icons of human evolution.


Effects of moisture and temperature during grain storage on the functional properties and isoflavone profile of soy protein concentrate.
The objective of this study was evaluate the effects of moisture and temperature during grain storage on the functional properties and isoflavone profile of soy protein concentrate. The protein concentrate was extracted from soybeans on the first day of storage and after 12months of storage, at 12 and 15% moisture and at temperatures of 11, 18, 25, and 32°C. The protein concentrate obtained from grains stored at 32°C showed decreased extraction yield (51.6% with 15% of moisture) and protein solubility (24.8% with 15% of moisture) with increased emulsifying capacity (52.2% with 12% of moisture) and foam formation, compared with sample obtained at the start of the storage period. The isoflavone profile showed a decrease in the concentrations of glycosylated, malonyl, and acetyl isoflavones and a corresponding increase in the concentrations of aglycone isoflavones, with the magnitude of these changes increasing with increasing storage temperature and moisture content.


Evaluation of quality of life and static balance in postmenopausal osteoporosis women after Tai Chi Chuan practice: an observational randomized case control study.
Post-menopausal osteoporosis women are at increased risk for skeletal fractures with higher mortality and lower quality of life. Some studies have reported fall risk reduction in the elderly after Tai chi practice. Tai chi is a weight bearing mind-body exercise that has been reported to positively influence bone mineral density and improve postural control in different pathologies. The aim of this observational randomized case control study is to evaluate the effect of Tai chi on balance and quality of life in postmenopausal women with osteoporosis. A total of 98 postmenopausal osteoporosis women, aged 70.6±8.2 years (mean and standard deviation), (mean T-score of the hip and spine were-2.9± 0.92 and -2.8±1.08), have been recruited in outpatients University Physical Medicine and Rehabilitation Hospital between June 2016 and September 2018. They have been randomized to a Tai group (56 patients, mean age 71.61±7.97 years) practiced 6-month Tai chi program, two times week, plus standard care or to a Control Group (42 patients, mean age 69.71±8.61 years) practiced usual care. Patients with oncological, neurological, cognitive, vestibular and visual diseases were excluded. Patients were evaluated at baseline (T0), prior Tai chi and after 6 month (T1) with 36-Item Short Form Health Survey (SF-36), and a stabilometric-standardized exam performed for the evaluation, respectively, of the quality of life and the static balance. The groups were homogenous at baseline. T1 evaluation showed better results in Tai chi group, in SF36 Physical functioning (p level: 0.021), Physical health pain (p level: 0.020), Physical composite score (p level: 0.003) scores, compared with control group. There were not significant differences between groups in stabilometric analysis. Tai chi group showed significant better stabilometric values at T1 compared with T0 in mean anterior-posterior (p level: 0.001) and medio-lateral (p level: 0.019) velocity, in perimeter (p level 0.001) , and in the area of the ellipse ( p level 0.006) in a within group analysis. Tai chi seemed to be effective in improving physical aspects of quality of life, in postmenopausal women with osteoporosis. Standing balance seems to increase after 6 months Tai chi program, in post-menopausal also if results were not significant. Further studies will be useful to measure effects of a Tai chi longer practice, as literature suggests, and a possible reduction of falling risk and fractures.


Novel agents for the treatment of acute myeloid leukemia in the older patient.
The incidence of acute myeloid leukemia (AML) increases with age, with a median age at diagnosis of 67 years. Older patients have inferior responses to chemotherapy, including not only lower complete remission rates but also short disease-free survival in those who do achieve complete remission. For older patients with a high likelihood of response to chemotherapy, recent data support dose intensification and strong consideration of allogeneic hematopoietic stem cell transplantation. For those unlikely to benefit from chemotherapy because of disease- and/or patient-related factors, novel agents and approaches are being pursued. Agents currently available or under study include the nucleoside analogs clofarabine and sapacitabine, the demethylating agents decitabine and azacitidine, the immunomodulatory agent lenalidomide, and the farnesyl transferase inhibitor tipifarnib. These agents may be administered in the outpatient setting, thus AML in older patients is increasingly becoming an outpatient diagnosis. Additionally, novel agents may prolong survival without inducing complete remissions, and therefore the goals and end points of therapy are also shifting. AML in older patients is a very active current area of investigation.


Application of enhanced bioreduction for hexavalent chromium-polluted groundwater cleanup: Microcosm and microbial diversity studies.
Hexavalent chromium (Cr6+) is a commonly found heavy metal at polluted groundwater sites. In this study, the effectiveness of Cr6+ bioreduction by the chromium-reducing bacteria was evaluated to remediate Cr6+-contaminated groundwater. Microcosms were constructed using indigenous microbial consortia from a Cr6+-contaminated aquifer as the inocula, and slow-releasing emulsified polycolloid-substrate (ES), cane molasses (CM), and nutrient broth (NB) as the primary substrates. The genes responsible for the bioreduction of Cr6+ and variations in bacterial diversity were evaluated using metagenomics assay. Complete Cr6+ reduction via the biological mechanism was observed within 80 days using CM as the carbon source under anaerobic processes with the increased trivalent chromium (Cr3+) concentrations. Cr6+ removal efficiencies were 83% and 59% in microcosms using ES and NB as the substrates, respectively. Increased bacterial communities associated with Cr6+ bioreduction was observed in microcosms treated with CM and ES. Decreased bacterial communities were observed in NB microcosms. Compared to ES, CM was more applicable by indigenous Cr6+ reduction bacteria and resulted in effective Cr6+ bioreduction, which was possibly due to the growth of Cr6+-reduction related bacteria including Sporolactobacillus, Clostridium, and Ensifer. While NB was applied for specific bacterial selection, it might not be appropriate for electron donor application. These results revealed that substrate addition had significant impact on microbial diversities, which affected Cr6+ bioreduction processes. Results are useful for designing a green and sustainable bioreduction system for Cr6+-polluted groundwater remediation.


An algorithm for converting rasters to quadtrees.
An algorithm is presented for constructing a quadtree for a binary image given its row-by-row description. The algorithm processes the image one row at a time and merges identically colored sons as soon as possible, so that a minimal size quadtree exists after processing each pixel. This method is spacewise superior to one which reads in an entire array and then attempts to build the quadtree.


Unexpected expansion of tRNA substrate recognition by the yeast m1G9 methyltransferase Trm10.
N-1 Methylation of the nearly invariant purine residue found at position 9 of tRNA is a nucleotide modification found in multiple tRNA species throughout Eukarya and Archaea. First discovered in Saccharomyces cerevisiae, the tRNA methyltransferase Trm10 is a highly conserved protein both necessary and sufficient to catalyze all known instances of m1G9 modification in yeast. Although there are 19 unique tRNA species that contain a G at position 9 in yeast, and whose fully modified sequence is known, only 9 of these tRNA species are modified with m1G9 in wild-type cells. The elements that allow Trm10 to distinguish between structurally similar tRNA species are not known, and sequences that are shared between all substrate or all nonsubstrate tRNAs have not been identified. Here, we demonstrate that the in vitro methylation activity of yeast Trm10 is not sufficient to explain the observed pattern of modification in vivo, as additional tRNA species are substrates for Trm10 m1G9 methyltransferase activity. Similarly, overexpression of Trm10 in yeast yields m1G9 containing tRNA species that are ordinarily unmodified in vivo. Thus, yeast Trm10 has a significantly broader tRNA substrate specificity than is suggested by the observed pattern of modification in wild-type yeast. These results may shed light onto the suggested involvement of Trm10 in other pathways in other organisms, particularly in higher eukaryotes that contain up to three different genes with sequence similarity to the single TRM10 gene in yeast, and where these other enzymes have been implicated in pathways beyond tRNA processing.


Transthoracic epicardial catheter ablation: indications, techniques, and complications.
Transthoracic epicardial catheter ablation is a useful supplemental or even preferred strategy to eliminate cardiac arrhythmias in the electrophysiology laboratory. The indication for this technique has extended to a diverse range of cardiac arrhythmias, including scar-related ventricular tachycardia (VT), idiopathic VTs, accessory pathways, atrial tachycardias, inappropriate sinus tachycardia, and atrial fibrillation, as the epicardial substrates of these tachyarrhythmias have become increasingly recognized. When endocardial ablation and epicardial ablation through the cardiac veins are unsuccessful, transthoracic epicardial ablation should be the next option. Intrapericardial access is usually obtained through a subxiphoidal pericardial puncture. This approach might not be possible in patients with pericardial adhesions caused by prior cardiac surgery or pericarditis. In such cases, a hybrid procedure involving surgical access with a subxiphoid pericardial window and limited anterior or lateral thoracotomy might be a feasible and safe method of performing epicardial catheter ablation in the electrophysiology laboratory. Potential complications associated with this technique include bleeding and collateral damage to the coronary artery and phrenic nerve. Although the risk of these complications is low, electrophysiologists who attempt epicardial catheter ablation should know the complications associated with this technique, how to minimize their occurrence, and how to rapidly recognize and treat the complications that they encounter. This review discusses the indications, techniques, and complications of transthoracic epicardial catheter ablation.


[Histologic and histomorphometric study of bone regeneration induced by beta-tricalcium phosphate (multicenter study)].
Autogenous bone graft insertion can effectively enhance the regeneration of the debilitated bone. However, bone graft can be harvested only by a second surgery, which is inconvenient for the patient and raises the possibility of many complications. The effect of an alloplastic bone-replacing material, beta-tricalcium phosphate and that of the autogenous bone graft were compared. The studies were performed on patients deriving from four European centers. In 20 edentulous patients, the alveolar ridge was extremely atrophied, so fixation of the denture was impossible. The base of the maxillary sinus was surgically elevated bilaterally by insertion of Cerasorb (beta-tricalcium phosphate) (experimental side) and by autogenous bone graft (control side). After surgery the recovery was controlled clinically and radiologically. After 6 months bone cylinders were excised from the grafted areas and implants were inserted into their place. 80 bone samples were embedded into resin, and the osteointegration of the grafts was studied histologically. The new bone density was measured by histomorphometry. Beta-tricalcium phosphate proved to be an effective bone replacing material with osteoconductivity, and was capable of gradual disintegration, providing space to the regenerating bone. The new bone density was similar on both sides without significant differences. After 6 months, insertion of the beta-tricalcium phosphate graft resulted in formation of stable bony bed apt to anchor of dental implants.


Goal setting in physiotherapy-led adult musculoskeletal care: A scoping review.
Goal setting is a key part of rehabilitation across various fields of physiotherapy. It is less clear what evidence exists to underpin its effectiveness and to practically guide its use within musculoskeletal physiotherapy. This scoping review provides an overview of current research regarding goal setting in adult physiotherapy-led musculoskeletal care with three aims: 1) to identify and analyse any gaps in the literature, 2) to identify relevant features of goal setting theory and 3) to make recommendations for future research. The principal research question was what does the literature tell us about the role of goal setting for adults over the age of 18 with musculoskeletal pain accessing outpatient physiotherapy services? The population, concept and context framework was used to define the inclusion criteria. Key definitions were adults over the age of 18 with musculoskeletal conditions, goal setting, and physiotherapy-led interventions. This scoping review followed the guidance set out by the Joanna Briggs Institute Manual for Evidence Synthesis. Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature Plus with Full Text, MEDLINE, American Psychological Association PsycInfo and the Cochrane Database of Systematic Reviews, Protocols and Trials were searched using pre-defined search criteria. Data were extracted from screened full-text articles and presented in basic statistical and narrative form. 41 articles were included in the review. Several broad themes and research methods were identified. The nature of the studies suggested that the clinical application of goal setting is complex and the depth of understanding is limited. Most studies suggested that goal setting is feasible and has a positive impact on outcomes. A common finding was a lack of clear definitions regarding goal setting terminology and approaches. Study samples were generally defined by biomedical categories, suggesting a pathoanatomical approach to researching a cognitive construct. Theoretical underpinning was lacking in many studies. No frameworks guiding goal setting in physiotherapy-led musculoskeletal rehabilitation have been identified. Goal setting is a popular tool within musculoskeletal outpatient physiotherapy. Further research is required to clarify its efficacy and provide guidance on its role and application in clinical practice.


HIV knowledge, attitudes and practices among college students in the United States.
Students enrolled at a Midwestern university in the United States were surveyed between February and April 2008 about their HIV knowledge, sources of information, attitude toward people living with HIV/AIDS, and their sexual behaviors. An anonymous questionnaire was sent to 1,000 students via Survey Monkey. Of the 650 respondents (65%) who provided complete information, 91.2% were white, 70.6% were female, 76.3% were seniors at the university and 94.7% were heterosexuals. Their average age was 22.5 years (SD +/- 4) with a range of 18 to 30 years. Although the majority of students (77.3%) reported to be very familiar with HIV/AIDS including its mode of transmission, important misconceptions still exist regarding HIV/AIDS. Several students either thought that mosquitoes transmit HIV/AIDS (14.2%) or did not know one way or the other (19.9%). About 43.1% were unsure about the existence of drugs that can prevent maternal to child transmission of HIV and 12% actually believed that these drugs do not exist. Moreover, despite the high prevalence of risky sexual behaviors among students, the majority of participants (86.8%) did not perceive themselves to be at risk for contracting HIV. As a result only 29.4% had ever been tested for HIV. Coexistence among college students of both misconceptions about the mode of HIV/AIDS transmission and denial about their vulnerability to contract this disease underscores the need for a proactive approach to address these challenges facing our youths.


How hospital ownership affects access to care for the uninsured.
This article addresses the effect of hospital ownership on the delivery of service to uninsured patients. It compares the volume of uninsured patients treated in for-profit and nonprofit hospitals by regarding hospital ownership and service as endogenous. Instrumental variable estimates are used to predict the percentage of patients who are uninsured, controlling for hospital ownership and service. The study shows that when for-profit and nonprofit hospitals are located in the same area, they serve an equivalent number of uninsured patients, but for-profit hospitals indirectly avoid the uninsured by locating more often in better-insured areas.


Reconstitution and purification of eukaryotic initiation factor 2B (eIF2B) expressed in Sf21 insect cells.
Eukaryotic initiation factor eIF2B plays a key role in the regulation of protein synthesis through its ability to catalyze the exchange of GDP bound to a second initiation factor, eIF2, for free GTP. In contrast to other GDP-GTP exchange factors (GEFs), which are often single subunit proteins, eIF2B consists of five dissimilar subunits. In the studies reported here the baculovirus expression vector system (BEVS) was used to express FLAG epitope tagged alleles for the alpha, beta, gamma, delta, and epsilon subunits of rat eIF2B in Sf21 cells. The eIF2B holoprotein was reconstituted in vivo by coexpression of all five subunits in Sf21 cells and was subsequently purified to greater than 98% homogeneity using a two-step procedure involving an anti-FLAG immunoaffinity column followed by gel filtration chromatography. The purified five-subunit eIF2B complex had high GEF activity as assayed by using [3H]GDP-bound to eIF2 as a substrate. Alternatively, eIF2B with high GEF activity was reconstituted in vitro by mixing crude cell lysates containing different eIF2B subunits. The latter results suggest that eIF2B activity in vivo could involve alterations in the concentration and/or the availability of individual subunits for holoprotein assembly. Overall, the results show the utility of the baculovirus-insect cell system for the expression, assembly, and purification of active recombinant multisubunit factors.


Ternary Complexes Stabilized by Chalcogen and Alkaline-Earth Bonds: Crucial Role of Cooperativity and Secondary Noncovalent Interactions.
High-level G4 calculations show that the strength of chalcogen interactions is enhanced dramatically if chalcogen compounds simultaneously form alkaline-earth bonds. This phenomenon is studied by exploring binary YX2 ⋅⋅⋅N-Base complexes and two types of ternary MCl2 ⋅⋅⋅YX2 ⋅⋅⋅N-Base, YX2 ⋅⋅⋅N-Base⋅⋅⋅MCl2 complexes, in which YX2 is a chalcogen compound (Y=S, Se; X=F, Cl), the N-Bases are sp, sp2 , and sp3 bases (NCH, HN=CH2 , NH3 ), and MCl2 are alkaline-earth BeCl2 or MgCl2 derivatives. Starting from the chalcogen-bonded complexes YX2 ⋅⋅⋅NH3 and YX2 ⋅⋅⋅HN=CH2 , the binding site of a new incoming alkaline-earth bond is found, surprisingly, to depend on the nature of the halogen atom attached to the chalcogen. For the YF2 binary complexes the association site is the F atom of the YF2 subunit, whereas for YCl2 it is the N atom of the nitrogen base. Regarding YX2 ⋅⋅⋅NCH complexes, N is the most favorable site for an alkaline-earth interaction in ternary complexes, regardless of which YX2 derivative is used. The explanation relies on the interplay of all the noncovalent interactions involved: the strong cooperativity between chalcogen and alkaline-earth bonds, and the appearance of secondary noncovalent interactions in the form of hydrogen bonds.


Serum Levels and Removal by Haemodialysis and Haemodiafiltration of Tryptophan-Derived Uremic Toxins in ESKD Patients.
Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, -0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (-72%, -39%, -43%, respectively), serum tryptophan levels increased, resulting in negative RR (-8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.


Na+- and cGMP-induced Ca2+ fluxes in frog rod photoreceptors.
We have examined the Ca2+ content and pathways of Ca2+ transport in frog rod outer segments using the Ca2+-indicating dye arsenazo III. The experiments employed suspensions of outer segments of truncated, but physiologically functional, frog rods (OS-IS), intact isolated outer segments (intact OS), and leaky outer segments (leaky OS with a plasma membrane leaky to small solutes, but with sealed disk membranes). We observed the following. Intact OS or OS-IS isolated and purified in Percoll-Ringer's solution contained an average of 2.2 mM total Ca2+, while leaky OS contained 2.0 mM total Ca2+. This suggests that most of the Ca2+ in OS-IS is contained inside OS disks. Phosphodiesterase inhibitors increased the Ca2+ content to approximately 4.2 mM in intact OS or OS-IS, whereas the Ca2+ content of leaky OS was not altered. Na-Ca exchange was the dominant pathway for Ca2+ efflux in both intact and leaky OS/OS-IS. The rate of Na-Ca exchange in intact OS/OS-IS was half-maximal between 30 and 50 mM Na+; at 50 mM Na+, this amounted to 5.8 X 10(7) Ca2+/OS X s or 0.05 mM total Ca2+/s. This is much larger than the Ca2+ component of the dark current. Other alkali cations could not replace Na+ in Na-Ca exchange in either OS-IS or leaky OS. They inhibited the rate of Na-Ca exchange (K greater than or equal to Rb greater than Cs greater than or equal to Li greater than TMA) and, as the inhibition became greater, a delay developed in the onset of Na-Ca exchange. The inhibition of Na-Ca exchange by alkali cations correlates with the prolonged duration of the photoresponse induced by these cations (Hodgkin, A. L., P. A. McNaughton, and B. J. Nunn. 1985. Journal of Physiology. 358:447-468). In addition to Na-Ca exchange, disk membranes in leaky OS showed a second pathway of Ca2+ transport activated by cyclic GMP (cGMP). The cGMP-activated pathway required the presence of alkali cations and had a maximal rate of 9.7 X 10(6) Ca2+/OS X s. cGMP caused the release of only 30% of the total Ca2+ from leaky OS. The rate of Na-Ca exchange in leaky OS amounted to 1.9 X 10(7) Ca2+/OS X s.(ABSTRACT TRUNCATED AT 400 WORDS)


The efficacy of inhaled nanoparticle tacrolimus in preventing rejection in an orthotopic rat lung transplant model.
The immunosuppressive efficacy of inhaled nanoparticle tacrolimus was compared with systemic tacrolimus in a rodent allogeneic lung transplant model. Sixteen rats underwent allogeneic left orthotopic lung transplantation and were divided into 3 treatment groups: (1) inhaled nanoparticle tacrolimus: 6.4 mg tacrolimus/6.4 mg lactose twice per day; (2) intramuscular tacrolimus: 1 mg/kg tacrolimus once per day; and (3) inhaled lactose: 6.4 mg of lactose twice per day. Five days after transplant, the rats were necropsied and underwent histologic rejection grading and cytokine analysis. Trough levels of tacrolimus were measured in allograft, blood, and kidney. Both intramuscular (n = 6) and nanoparticle tacrolimus (n = 6) rats displayed lower histologic grades of rejection (mean scores 3.4 ± 0.6 and 4.6 ± 0.9, respectively) when compared with lactose rats (n = 4) (mean score 11.38 ± 0.5, P = .07). Systemic tacrolimus trough levels (median) were lower in nanoparticle tacrolimus-treated rats versus intramuscular-treated rats (29.2 vs 118.6 ng/g; P < .001 in kidney, and 1.5 vs 4.8 ng/mL; P = .01 in blood). Inhaled nanoparticle tacrolimus provided similar efficacy in preventing acute rejection when compared with systemic tacrolimus while maintaining lower systemic levels.


Cardiac allograft systolic function. Is the aetiology (ischaemic or idiopathic) a determinant of ventricular function in the heart transplant patient?
The natural history of the LV systolic function (LV-SF) and functional capacity of survivors of heart transplantation (Htx) has not been defined. Some investigators suggest that SF may be different in recipients with different pre-transplant aetiologies: ischaemic or dilated, idiopathic disease. Routine transthoracic echocardiograms (TTE) were performed during a 1-year follow-up in 48 Htx recipients (total 864 examinations; mean 18/patient). Patients were divided into two groups based on pre-transplant diagnosis: ischaemic (CAD-CMP: n=13, age 54+/-1.7 years, 23% females) and idiopathic dilated cardiomyopathy (ID-CMP: n=35, age 51+/-2.3 years, 26% females). Patients with valvular and toxic aetiology were excluded. All patients underwent left ventriculography (VENT) 12-15 months after Htx. The majority of 1-year survivors of Htx maintained normal LV-SF: mean LVEF 65+/-4% by echocardiography and 68+/-3% by ventriculography, but in the ID-CMP group LVEF was significantly higher: 67+/-4% vs. 62+/-4% (TTE) and 77+/-4% vs. 60+/-4% (VENT), without significant differences in functional capacity (NYHA). 82.9% of ID-CMP patients had LVEF >65% vs. 39% in CAD-CMP. The incidence of acute cellular rejection, freedom from cardiac vasculopathy, renal failure, diabetes, hypertension and pre-transplant alloantibody level was similar. Our study shows a strong correlation between pre-transplant heart disease and the systolic function of the cardiac allograft at 1-year follow-up.


Pain indicators for persisting pain in hospitalized infants in a South African setting: an explorative study.
In the developing world, there is a high incidence of human immunodeficiency virus (HIV), gastroenteritis, pneumonia, meningitis, and other inflammatory diseases in infants, the conditions of which may induce persisting pain. The primary objective was to estimate the reliability and validity of the Touch Visual Pain (TVP) scale to measure persisting pain. This prospective observational study was performed in hospitalized 0-3-year-old infants in South Africa. The Numeric Rating Scale (NRS) pain, NRS distress, and the TVP scale were applied and scores were compared. The TVP scale consists of 10 behavioral indicators scored as present or not present. Associations between the different scales were tested with logistic regression analyses. We analyzed 337 assessments in 151 patients. The NRS pain score was 4 or higher in 82 (24%) assessments. The NRS distress score was 4 or higher in 242 (72%) assessments. The mean TVP score was 3.7 (SD = 1.6). Four TVP items were statistically significantly associated with NRS pain; three other TVP items with NRS distress. The behaviors "cry/moaning" and "alertness" were also significantly associated with NRS distress. Two TVP items were not sensitive to assess pain or distress and were replaced in a revised TVP version. We conclude that our study identified sensitive and specific indicators of persisting pain in hospitalized children under the age of 3 years in a South African setting. Psychometric properties of the revised TVP need to be studied before its use in clinical practice can be recommended.


Meaningful Human Control over Autonomous Systems: A Philosophical Account.
Debates on lethal autonomous weapon systems have proliferated in the past 5 years. Ethical concerns have been voiced about a possible raise in the number of wrongs and crimes in military operations and about the creation of a "responsibility gap" for harms caused by these systems. To address these concerns, the principle of "meaningful human control" has been introduced in the legal-political debate; according to this principle, humans not computers and their algorithms should ultimately remain in control of, and thus morally responsible for, relevant decisions about (lethal) military operations. However, policy-makers and technical designers lack a detailed theory of what "meaningful human control" exactly means. In this paper, we lay the foundation of a philosophical account of meaningful human control, based on the concept of "guidance control" as elaborated in the philosophical debate on free will and moral responsibility. Following the ideals of "Responsible Innovation" and "Value-sensitive Design," our account of meaningful human control is cast in the form of design requirements. We identify two general necessary conditions to be satisfied for an autonomous system to remain under meaningful human control: first, a "tracking" condition, according to which the system should be able to respond to both the relevant moral reasons of the humans designing and deploying the system and the relevant facts in the environment in which the system operates; second, a "tracing" condition, according to which the system should be designed in such a way as to grant the possibility to always trace back the outcome of its operations to at least one human along the chain of design and operation. As we think that meaningful human control can be one of the central notions in ethics of robotics and AI, in the last part of the paper, we start exploring the implications of our account for the design and use of non-military autonomous systems, for instance, self-driving cars.


Brian Blundell Boycott, 10 December 1924 - 22 April 2000.
Brian Blundell Boycott was an outstanding zoologist and neurobiologist. His early research (1947-52), at the Anatomy Department of University College London and at the Stazione Zoologica in Naples, Italy, was on learning and memory in cephalopods and the functional architecture of the octopus brain. From 1952 to 1970 he was a teacher of zoology and later neurobiology at University College London (Zoology Department). Brain's research interests changed in the early 1960s, when he began studying the mammalian retina. Over a period of 35 years he produced many seminal papers that laid the foundation for our modern understanding of the cell types and synaptic connections that form the basis of parallel processing in the retina. In 1970 Brian moved to the Medical Research Council (MRC) Biophysics Unit at King's College London, from which he retired as Director at the end of 1989. He continued to be an active researcher at Guy's Hospital Medical School (1990-97) and in the Institute of Ophthalmology, University College London (1997-2000). Brian was a modest and kind person, generous in sharing ideas and material; he liked to interact and cooperate with other people and was very supportive of young scientists.


The yellow nail syndrome.
The yellow nail syndrome is a rare clinical entity which combines three main features: yellow discolouration of the nails, chronic lymphedema, and pleural effusion. Since 1994, chronic rhinosinusitis is associated in this syndrome. A lot of other pathologic conditions are often present. The most frequent are: bronchiectasis, recurrent pneumonia, pericardic effusion, humoral immunity deficiencies. Among the etiopathogeneses advocated, the more credible ones deal with changes of the lymphatic network with hypoplastic vessels leading to inadequate adaptation, after local damage of the tissues. When this syndrome is suspected on the basis of the examination of the nails, an extensive investigation (dermatologic, pneumologic, lymphographic, biologic) has to be launched to exclude underlying neoplasma, or autoimmune disease, frequently associated with this syndrome. The treatment is controversial and poorly effective. Vitamin A and E, Zn sulfate and itraconazole are drugs the most often advised. Spontaneous healing is reported in 30% of the cases. Endoscopic endonasal surgery in such cases, when the sinusal mucosa is involved, is controversial and its outcome is not yet documented.


Importance of pouch size in laparoscopic Roux-en-Y gastric bypass: a cohort study of 14,168 patients.
Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most common bariatric procedures worldwide, but the importance of gastric pouch size is still under debate. We have studied how pouch size affects risk of marginal ulcer and excess body mass index loss (EBMIL%) at 6 weeks and 1 year postoperatively. Scandinavian Obesity Surgery Registry included 14,168 LRYGB patients with linear stapled gastrojejunostomies, having complete pre- and postoperative data concerning length of stapler needed to complete the gastric pouch, incidence of marginal ulcers and weight loss. LRYGB technique in Sweden is highly standardized, and total length of stapler was used as a proxy for pouch size. Mean length of stapler used for the pouch was 145 mm. At 1 year, symptomatic marginal ulcers were noted in 0.9 % of the patients. The relative risk of marginal ulcer increased by 14 % (95 % confidence interval 9-20 %), for each centimeter of stapler used for the pouch. Body mass index (BMI) was reduced from 42.4 ± 5.1 to 36.1 kg/m(2) at 6 weeks and 28.9 kg/m(2) at 1 year. The total length of stapler predicted EBMIL% at 6 weeks but not at 1 year. Female gender, low preoperative BMI, young age and absence of diabetes predicted better EBMIL% at 1 year. A smaller pouch reduces the risk of marginal ulcers, but does not predict better weight loss at 1 year. Additional stapling should be avoided as each extra centimeter increases the relative risk of marginal ulcers by 14 %.


Anonymous peer assessment of medication management reviews.
To investigate whether pharmacy students' anonymous peer assessment of a medication management review (MMR) was constructive, consistent with the feedback provided by an expert tutor, and enhanced the students' learning experience. Fourth-year undergraduate pharmacy students were randomly and anonymously assigned to a partner and participated in an online peer assessment of their partner's MMR. An independent expert graded a randomly selected sample of the MMR's using a schedule developed for the study. A second expert evaluated the quality of the peer and expert feedback. Students also completed a questionnaire and participated in a focus group interview. Student peers gave significantly higher marks than an expert for the same MMR; however, no significant difference between the quality of written feedback between the students and expert was detected. The majority of students agreed that this activity was a useful learning experience. Anonymous peer assessment is an effective means of providing additional constructive feedback on student performance on the medication review process. Exposure to other students' work and the giving and receiving of peer feedback were perceived as valuable by students.


Sonotubometric Assessment for Severity of Patulous Eustachian Tube.
To investigate the relationship between the morphological patency of the eustachian tube (ET) and sound transmission via the ET. Retrospective chart review and model experiment. Tertiary referral center. A total of 56 ears of 28 patients (9 men and 19 women, aged from 12 to 82 yr, mean 40.4 ± 21.5 yr) who underwent sonotubometric measurement using postural change as well as computed tomography (CT) of the ET in the sitting position, including 26 ears with definite patulous ET, 9 ears with possible patulous ET, and 21 ears without patulous ET. Commercial equipment for sonotubometry (JK-05A; RION Co., Ltd., Kokubunji, Tokyo, Japan) was used in the following two investigations. Retrospective survey: sound patency of 7 kHz band noise via the ET was assessed by comparison of acoustic transfer function via the ET in the sitting and forward-bending positions. Sound patency via the ET was compared with morphological patency of the ET (cross-sectional area in the narrowest portion) assessed by three-dimensional CT of the ET in the sitting position. Model experiment: effect of the ET caliber on the acoustic transfer function was examined using a simple model constructed with two truncated syringes with silicone barrels and a narrow connecting tube. Sound patency assessed by sonotubometry was well correlated with the cross-sectional area at the narrowest portion of the ET in the sitting position (r = 0.786, p < 0.001). Correlation between the sound patency via the narrow tube and the caliber of the tube was also confirmed by the model experiment. Sound patency assessed by sonotubometry using 7 kHz band noise could be useful to predict the morphological severity of patulous ET.


Cushing's syndrome and acute lymphoblastic leukemia.
Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences.


Endothelial nitric oxide synthase G894T, intron 4 VNTR, and T786C polymorphisms in retinopathy of prematurity.
Our objective in this study was to assess the association between eNOS gene, that achieves synthesis of nitric oxide especially in the endothelial cells known to have an important role in angiogenesis and vasculogenesis, G894T, intron 4 VNTR (27-bp repeat) and T786C functional polymorphisms and retinopathy of prematurity (ROP), which is an important cause of morbidity in premature or low birth weight babies. A total of 139 babies who were followed up in our neonatal intensive care unit because of premature birth in our hospital or admitted to our unit. 69 of them had retinopathy of prematurity and comprised the patients group. The remaining 70 babies who did not have ROP comprised the control group. An additional of 1 ml of blood samples were drawn from babies who were in the study groups during routine laboratory analysis. eNOS gene polymorphisms were determined by using polymerase chain reaction method. eNOS G894T, intron 4 VNTR and T786C gene polymorphisms did not differ between the patient and control groups (p > 0.05). Using logistic regression analysis; while gender did not differ between two groups; gestational age, birth weight, time on mechanical ventilation differ between two groups. After adjustment for variables other than eNOS gene polymorphisms, we found no significant difference in the genotype distribution of eNOS G894T, intron 4 VNTR and T786C polymorphisms (p > 0.05). We observed no association between ROP and eNOS gene polymorphisms but needs more investigation.


Acceptability and performance of the menstrual cup in South Africa: a randomized crossover trial comparing the menstrual cup to tampons or sanitary pads.
In low-income settings, many women and girls face activity restrictions during menses, owing to lack of affordable menstrual products. The menstrual cup (MC) is a nonabsorbent reusable cup that collects menstrual blood. We assessed the acceptability and performance of the MPower® MC compared to pads or tampons among women in a low-resource setting. We conducted a randomized two-period crossover trial at one site in Durban, South Africa, between January and November 2013. Participants aged 18-45 years with regular menstrual cycles were eligible for inclusion if they had no intention of becoming pregnant, were using an effective contraceptive method, had water from the municipal system as their primary water source, and had no sexually transmitted infections. We used a computer-generated randomization sequence to assign participants to one of two sequences of menstrual product use, with allocation concealed only from the study investigators. Participants used each method over three menstrual cycles (total 6 months) and were interviewed at baseline and monthly follow-up visits. The product acceptability outcome compared product satisfaction question scores using an ordinal logistic regression model with individual random effects. This study is registered on the South African Clinical Trials database: number DOH-27-01134273. Of 124 women assessed, 110 were eligible and randomly assigned to selected menstrual products. One hundred and five women completed all follow-up visits. By comparison to pads/tampons (usual product used), the MC was rated significantly better for comfort, quality, menstrual blood collection, appearance, and preference. Both of these comparative outcome measures, along with likelihood of continued use, recommending the product, and future purchase, increased for the MC over time. MC acceptance in a population of novice users, many with limited experience with tampons, indicates that there is a pool of potential users in low-resource settings.


[Insertion mutagenesis in Bacillus subtilis (Marmur)].
A method for obtaining mutations in Bacillus subtilis using integration into the chromosome of the plasmid pHV60 ligated to chromosomal DNA fragments was developed. Auxotrophic mutants acquire, in addition, chloramphenicol-resistance, due to insertion of appropriate plasmid determinants. Chromosomal localization was established and the properties of several mutants were studied.


A young man with a renal colic.
We report the case of a 35-year-old man with no cardiovascular morbidity, presenting with acute flank pain, microscopic haematuria and normal blood pressure. Initially diagnosed as a ureteral colic, the patient was recovered 6 weeks later with severe hypertensive crisis. Further investigations revealed a massive renal infarction secondary to medial fibromuscular dysplasia (FMD). Several aspects of this presentation are intriguing. Renal infarcts are usually seen in older patients having cardiac problems and/or major atheromatous plaques. In addition, FMD is mainly observed in young females and rarely progresses to renal artery occlusion. Furthermore, in this case, FMD remained silent until the acute renal infarction occurred, despite a significant kidney size reduction at the time of diagnosis. Finally, the observation of a delayed hypertensive response to a major renovascular insult provides incentives to discuss possible pathophysiological mechanisms involved in renovascular hypertension.


Synthesis of amphiphilic phenylazophenyl glycosides and a study of their liquid crystal properties.
Several 4-(4'-N,N-didodecylaminophenylazo)phenyl 1,2-trans glycosides 5a-e with various carbohydrate heads (beta-D-gluco, beta-D-galacto, beta-lacto, beta-D-xylo, and alpha-D-manno) have been synthesized. The key step was the formation of phenyldiazonium tetrafluoroborates 2a-e from the per-O-acetylated 4-aminophenyl glycosides 1a-e. These salts were condensed with N,N-didodecylaniline under phase transfer conditions and the per-O-acetylated 4-(4'-N,N-didodecylaminophenylazo)phenyl 1,2-trans glycosides 4a-e were fully de-O-acetylated by the Zemplén method. The self-organizing liquid crystal properties of the compounds were investigated by a variety of techniques, including polarized light microscopy, differential scanning calorimetry, and X-ray diffraction. All but one of the materials exhibited smectic A, lamellar phases. Remarkably, the glucose derivative exhibited a rectangular disordered columnar phase. This result has implications with respect to the induced curvature created by the recognition processes of the glucose headgroup relative to the other sugar moieties and to the prevalence of various glycolipids in cell membranes


Physical activity and stress management during COVID-19: a longitudinal survey study.
Physical activity (PA) during COVID-19 shelter-in-place (SIP) may offset stress. This study examined associations between PA, stress and stress management strategies during SIP. Participants (N = 990) from a cohort of Northern California adults completed surveys during early SIP (3/23/20-4/2/20) and mid-SIP (4/24/20-5/8/20). Participants self-reported past-month PA (meeting vs. not meeting guidelines), changes in stress (decreased/unchanged vs. increased) and use (yes/no) of 10 stress management strategies. We tested differences in mid-SIP stress and stress management strategies by PA, and differences in mid-SIP stress by stress management strategies. Compared to participants inactive at mid-SIP, active participants reported less stress (AOR = 0.60 [0.45, 0.81]). Active participants were more likely to manage stress using outdoor PA, indoor PA, yoga/meditation/prayer, gardening, and reading (AORs > 1.42), and less likely to sleep (AOR = 0.65 [0.48, 0.89]) or eat ([AOR = 0.48 [0.35, 0.66]) more. Managing stress using outdoor PA, indoor PA or reading was associated with lower stress; managing stress using TV/movies, sleeping or eating was associated with increased stress (ps < 0.05). Meeting PA guidelines during SIP was associated with less stress. Inactive participants reported greater sleeping and eating to cope; active participants used active stress management strategies. Engagement in physically active stress management was associated with lower stress.


[Content and utilization of testosterone in the cardiac and skeletal muscles of male rats during physical exercise].
They influenced differently the content, transport and utilization of testosterone (T) in the body. The strength training resulted in a 2.5-3-fold increase of the T-content and binding capacity of blood proteins as compared with untrained animals, and a 1.5-2.0-fold increase of these characteristics as compared with untrained animals. As a result of PE 3H-T incorporation in 10 investigated tissues and organs including muscles increased 2-fold. A pharmacokinetic study showed that androgen half-life in the body increased from 1 h 35 min to 2 h 16 min under PE. The training did not change the T content in the active skeletal and heart muscles. The T and androgen receptor content in the muscle cytosol did not change after training.


Cannabis use disorder and increased risk of arrhythmia-related hospitalization in young adults.
Recent observations indicate that cannabis use can result in cardiovascular complications including arrhythmias. We studied the relationship between cannabis use disorder (CUD) and arrhythmia hospitalization. We conducted a retrospective analysis of the Nationwide Inpatient Sample (2010-2014). Patients (age 15-54) with a primary diagnosis for arrhythmia (N = 570,556) were compared with non-arrhythmia (N = 67,662,082) inpatients for odds ratio (OR) of CUD by the logistic regression model, adjusted for demographics and comorbid risk factors. The incidence of CUD in arrhythmia inpatients was 2.6%. Among cannabis users, the most prevalent arrhythmia was atrial fibrillation (42%), followed by other arrhythmias (24%) and atrial flutter (8%). Patients with CUD were younger (15-24 years, OR: 4.23), male (OR: 1.70), and African American (OR: 2.70). CUD was associated with higher odds of arrhythmia hospitalization in the young population, 1.28 times in 15-24 years (95% confidence interval [CI]: 1.229-1.346) and 1.52 times in 25-34 years (95% CI: 1.469-1.578). With the growing legalization in the United States, there is an increased use of medicinal/recreational cannabis. This is the first national study to our knowledge that found that CUD is associated with a 47%-52% increased likelihood of arrhythmia hospitalization in the younger population and the risk of association was controlled for potential confounders including other substances. The fact that atrial fibrillation is the most prevalent arrhythmia is of special concern since it can result in stroke and other embolic events. Physicians need to familiarize themselves with cannabis abuse or dependence as a risk factor for arrhythmia.


[Methods of heparin therapy in surgical patients with thrombohemorrhagic syndrome].
The results of comparative study of different heparin medications efficacy in patients with thrombohemorrhagic syndrome (THS) are presented. The study was conducted in 286 patients with THS as a result of peritonitis of various etiology (174 patients), massive hemorrhage, shock, microcirculation disorders (112 patients). Heparin therapy carried out in 249 patients (87.1%), 37 patients (12.9%) had no heparin therapy./ In "heparin" group 193 patients (77.5%) received low molecular weight heparin (LMWH), 56 patients (22.5%) took unfractionated heparin (UFH). LWMH demonstrated high efficiency with fewer hemorrhagic complications in comparison with UFH/.


Neostriatal Neuronal Activity Correlates Better with Movement Kinematics under Certain Rewards.
This study investigated how the activity of neostriatal neurons is related to the kinematics of movement when monkeys performed visually and vibratory cued wrist extensions and flexions. Single-unit recordings of 142/236 neostriatal neurons showed pre-movement activity (PMA) in a reaction time task with unpredictable reward. Monkeys were pseudo-randomly (75%) rewarded for correct performance. A regression model was used to determine whether the correlation between neostriatal neuronal activity and the kinematic variables (position, velocity, and acceleration) of wrist movement changes as a function of reward contingency, sensory cues, and movement direction. The coefficients of determination (CoD) representing the proportion of the variance in neuronal activity explained by the regression model on a trial by trial basis, together with their temporal occurrences (time of best regression/correlation, ToC) were compared across sensory modality, movement direction, and reward contingency. The best relationship (correlation) between neuronal activity and movement kinematic variables, given by the average coefficient of determination (CoD), was: (a) greater during trials in which rewards were certain, called "A" trials, as compared with those in which reward was uncertain called ("R") trials, (b) greater during flexion (Flex) trials as compared with extension (Ext) trials, and (c) greater during visual (VIS) cued trials than during vibratory (VIB) cued trials, for the same type of trial and the same movement direction. These results are consistent with the hypothesis that predictability of reward for correct performance is accompanied by faster linkage between neostriatal PMA and the vigor of wrist movement kinematics. Furthermore, the results provide valuable insights for building an upper-limb neuroprosthesis.


Effects of sexual harassment on advancement of women in academic medicine: A multi-institutional longitudinal study.
Sexual harassment of women in academic medicine may impede advancement and productivity. This study analyzes the longitudinal effects of sexual harassment on academic advancement and productivity among women. We undertook a longitudinal analysis to predict effects of sexual harassment reported in 1995 on career outcomes measured in 2012-13, among a sample of women in academic medicine (N = 1273) recruited from 24 U.S. medical schools. Measures included survey data from 1995 on sexual harassment (predictor), and 2012-2013 data on retention in academic medicine, rank, leadership positions, and refereed publications (outcomes), captured from surveys and public records. We used multivariable models to test effects of sexual harassment on study outcomes, adjusting for socio-demographics, employment-related variables, and gender discrimination. In 1995, 54% of women reported any workplace sexual harassment, and 32% of women reported severe harassment (e.g., threats or coercive sexual advances) in the workplace. Multivariable regression models showed no significant effects of sexual harassment. However, severe sexual harassment was associated with higher odds of attaining full professorship by 2012-2013 (AOR: 1·70; 95% CI 1·03, 2·80; p = 0·04). Contrary to our hypothesis, women reporting severe workplace harassment in 1995 were more rather than less likely to advance to full professor. Women seeking advancement may be more vulnerable to sexual harassment in academic medicine vis a vis greater exposure to those who abuse their position of authority. NIvH R01GM088470; Doris Duke Foundation 2016D007145; BMGF OPP1163682.


An accurate and sensitive effervescence-assisted liquid phase microextraction method for the determination of cobalt after a Schiff base complexation by slotted quartz tube-flame atomic absorption spectrophotometry in urine samples.
In this study, an accurate analytical method development for cobalt determination in urine samples was described. The method is based on the mass transfer of the target analytes to the organic phase from the aqueous phase by the dispersing extractant throughout the solution with the aid of CO2 bubbles prior to sample measurement by using a slotted quartz tube flame atomic absorption spectrophotometer. An extractor (1-decanol) dropped effervescent tablet (anhydrous sodium carbonate and sodium dihydrogen phosphate dihydrate mixture) was used in order to separate/preconcentrate cobalt after complexation of cobalt ions in aqueous solution with the Schiff base ligand. The parameters affecting the extraction output such as complexing conditions (pH, ligand concentration, and volume) and extraction conditions (extraction solvent type and volume, extraction temperature, and heating duration, NaOH volume and mixing period) were optimized to lower the detection limit. The limit of detection and quantification values under optimized experimental and instrumental conditions were determined as 3.7 μg L-1 and 12 μg L-1, respectively with high linearity with respect to the dynamic range between 15 and 300 μg L-1. The enhancement factor obtained with the developed method was calculated as 83 fold. The pretreatment process was applied to urine samples in order to test the convenience of the developed method in urine samples for the determination of cobalt at low levels. The high percentage recovery results of 96-97% for four different concentrations of spiked urine samples indicated the proposed method's sufficient sensitivity for analyte determination in such a complex matrix.


A recombinant plasmid of composite cysteine proteinase inhibitor/glyceraldehyde-3-phosphate dehydrogenase gene of periodic Brugia malayi functions on DNA immunity in the host.
Both cysteine proteinase inhibitors (CPIs) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) play important roles in the pathogenesis of parasites and their relationship with the hosts. We constructed a new eukaryotic recombinant expression plasmid pcDNA3.1(+)-BmCPI/BmGAPDH of periodic Brugia malayi for investigation of the DNA vaccine-elicited immune responses. We cloned a gene encoding the CPIs and GAPDH from periodic B. malayi into vector pcDNA3.1. The composited plasmid or the control was injected into the tibialis anterior muscle of the hind leg in BALB/c mice, respectively. The target genes were detected by reverse transcription-polymerase chain reaction in muscle tissues. The stimulation index (SI) of T-lymphocyte proliferation and the levels of interferon-gamma (INF-g) and interleukin-4 ( IL-4) in serum were detected by thiazolyl blue tetrazolium blue and enzyme-linked immunosorbent assays. The pcDNA3.1(+)-BmCPI/BmGAPDH was amplified from muscle tissues of the mice after immunisation. The SI of the immunised group was significantly higher than that of the two control groups (P < 0.05). The levels of INF-g and IL-4 of pcDNA3.1(+)-BmCPI/BmGAPDH group were both higher than those of the two control groups (P < 0.05). The level of INF-g of pcDNA3.1(+)-BmCPI/BmGAPDH group was significantly higher than that of pcDNA3.1(+)-BmCPI/CpG group (P < 0.05). We conclude that the recombinant plasmid pcDNA3.1(+)-BmCPI/BmGAPDH could elicit specific humoural and cellular immune responses in mice.


Immunotherapeutic and oncolytic viral therapeutic strategies in pancreatic cancer.
Pancreatic adenocarcinoma is an aggressive disease with dismal outcomes despite recent advances using combination chemotherapeutic regimens. The lack of an adequate immune response to malignant cells has been identified as a factor associated with tumor aggressiveness and refractoriness to systemic treatment. Preclinical and early clinical studies have identified numerous immunotherapeutic and oncolytic viral therapeutic strategies aimed towards amplifying the immune reaction to pancreatic cancer and have established encouraging results. Promising antitumor efficacy has been observed both in vitro and in vivo with many of these approaches. These novel applications have also led to improved understanding of the process of pancreatic tumor growth and invasion, knowledge of the tumor microenvironment and have pioneered further investigations of similar therapies. Here we review both immunotherapeutic and oncolytic viral therapeutic strategies in pancreatic cancer.


Estrogen enhances vasoconstrictive remodeling after injury in male rabbits.
The complete spectrum of estrogen vascular effects remains unclear. In particular, estrogen effects in the vascular response to profound injury in males have not been explored in detail. Therefore, we submitted 44 male New Zealand rabbits weighing 3.4 +/- 0.6 kg to overdistention balloon injury of the right iliac artery. Rabbits were given 17beta-estradiol (5.45 micromol/day, sc) or vehicle for 7 days before and 14 days after injury, when the arteries were examined by post-mortem histomorphometry. Arteriographic caliber was assessed in vivo at baseline and before sacrifice. On day 14 after injury, in vivo arteriographic caliber (baseline = 2.44 +/- 0.43 mm) was decreased by 23.1 +/- 0.1% in controls and by 44.5 +/- 0.1% in estrogen-treated rabbits (P < 0.001). Neither the neointimal area nor the neointima/media area ratio changed after estrogen treatment. Collagen fraction was increased in the media and neointima of estrogen-treated rabbits vs control (1.38 +/- 1.30 vs 0.35 +/- 0.67, respectively, P = 0.01). Taken together, these findings suggest that estrogen increased negative vascular remodeling. Transcription of endothelial and inducible nitric oxide synthases (eNOS and iNOS) was analyzed by RT-PCR. eNOS mRNA expression was marginally increased after estrogen (P = 0.07) and injury. iNOS mRNA was increased 2- to 3-fold on day 14 after injury. With estrogen treatment, iNOS mRNA increased in uninjured arteries and exhibited a further 5.5-fold increase after injury. We concluded that estrogen increased lumen loss after balloon injury in male rabbits, likely by increased negative remodeling, which may be related to increased iNOS transcriptional rates.


Measuring and Modelling the Effect of Inorganic Phosphate on Cross-bridge Mechanics in Human Cardiac Muscle.
Many common chronic diseases operate at the intersection of metabolic and cardiovascular dysfunction. In order to model the effects of these diseases and investigate underlying causes we are developing a cardiomyocyte model which incorporates both the mechanics and metabolic factors that underlie work done by the heart. In this paper we present the first experimental results from our study measuring mechanical properties in human cardiac trabeculae, including the effect of inorganic phosphate (Pi) on the complex modulus at 37 °C. Extending our previous mathematical model, we have developed a computationally efficient model of cardiac cross-bridge mechanics which is sensitive to changes in cellular Pi. This extended model was parameterised with human cardiac complex modulus data. It captured the changes to cardiac mechanics following an increase in Pi concentration that we measured experimentally, including a reduced elastic modulus and a right-shift in frequency. The human cardiac trabecula we studied had a low sensitivity to Pi compared to what has been previously reported in mammalian cardiac tissue, which suggests that the muscle may have cellular compensatory mechanisms to cope with elevated Pi levels. This study demonstrates the feasibility of our experimental-modelling pipeline for future investigation of mechanical and metabolic effects in the diseased human heart.Clinical Relevance- This study presents the first measurement of the effect of Pi on the stiffness frequency response of human cardiac tissue and extends an experimental-modelling framework appropriate for investigating effects of disease on the human heart.


Ultrahigh molecular weight polyethylene particles have direct effects on proliferation, differentiation, and local factor production of MG63 osteoblast-like cells.
Small particles of ultrahigh molecular weight polyethylene stimulate formation of foreign-body granulomas and bone resorption. Bone formation may also be affected by wear debris. To determine if wear debris directly affects osteoblasts, we characterized a commercial preparation of ultrahigh molecular weight polyethylene (GUR4150) particles and examined their effect on MG63 osteoblast-like cells. In aliquots of the culture medium containing ultrahigh molecular weight polyethylene, 79% of the particles were less than 1 microm in diameter, indicating that the cells were exposed to particles of less than 1 microm. MG63 cell response to the particles was measured by assaying cell number, [3H]thymidine incorporation, alkaline phosphatase specific activity, osteocalcin production, [35S]sulfate incorporation, and production of prostaglandin E2 and transforming growth factor-beta. Cell number and [3H]thymidine incorporation were increased in a dose-dependent manner. Alkaline phosphatase specific activity, a marker of cell differentiation for the cultures, was significantly decreased, but osteocalcin production was not affected. [35S]sulfate incorporation, a measure of extracellular matrix production, was reduced. Prostaglandin E2 release was increased, but transforming growth factor-beta production was decreased in a dose-dependent manner. This shows that ultrahigh molecular weight polyethylene particles affect MG63 proliferation, differentiation, extracellular matrix synthesis, and local factor production. These effects were direct and dose dependent. The findings suggest that ultrahigh molecular weight polyethylene wear debris particles with an average size of approximately 1 microm may inhibit bone formation by inhibiting cell differentiation and reducing transforming growth factor-beta production and matrix synthesis. In addition, increases in prostaglandin E2 production may not only affect osteoblasts by an autocrine pathway but may also stimulate the proliferation and activation of cells in the monocytic lineage. These changes favor decreased bone formation and increased bone resorption as occur in osteolysis.


Competition-induced downregulation of symbiotic nitrogen fixation.
Controlled experiments at the level of individual plants show that legume species use different strategies for the regulation of symbiotic dinitrogen fixation in response to nitrogen availability. These strategies were suggested to improve legume fitness in the context of the plant community, although rarely studied at this level. We evaluated how nitrogen availability and conspecific vs heterospecific interactions influenced the strategy of regulation of nitrogen fixation. We grew two species of herbaceous legumes representing two different strategies of regulation without interaction, under treatments of deficient and sufficient nitrogen availability, with conspecific or heterospecific interaction. We found that Hymenocarpus circinnatus maintained a facultative strategy of downregulating nitrogen fixation when nitrogen was available under both con- and heterospecific interactions, as was also found for this species when grown alone. Vicia palaestina also downregulated nitrogen fixation under both con- and heterospecific interactions but did not regulate fixation when grown alone. Our results showed that under nitrogen limitation, interaction with a neighboring plant reduced fitness, reflecting a competitive effect. Our findings suggest that when interacting with other plants, downregulation of nitrogen fixation is more likely, therefore reducing the energetic cost of fixation, and improving plant performance in competitive ecological communities, especially when nitrogen is available.


Morbidity and health care resource utilization in HIV-infected children after antiretroviral therapy initiation in Côte d'Ivoire, 2004-2009.
We describe severe morbidity and health care resource utilization (HCRU) among HIV-infected children on antiretroviral therapy (ART) in Abidjan, Côte d'Ivoire. All HIV-infected children enrolled in an HIV-care program (2004-2009) were eligible for ART initiation until database closeout, death, ART interruption, or loss to follow-up. We calculated incidence rates (IRs) of density per 100 child-years (CYs) for severe morbidity, HCRU (outpatient care and inpatient care), and associated factors using frailty models with a Weibull distribution. Of 332 children with a median age of 5.7 years and median follow-up of 2.5 years, 65.4% were severely immunodeficient by World Health Organization (WHO) criteria, and all received cotrimoxazole prophylaxis. We recorded 464 clinical events in 228 children; the overall IR was 57.6/100 CYs [95% confidence interval (CI): 52.1 to 62.5]. Severe morbidity was more frequent in children on protease inhibitor (PI)-based ART compared to those on other regimens [adjusted hazards ratio (aHR): 1.83; 95% CI: 1.35 to 2.47] and to those moderately/severely immunodeficient compared to those not (aHR: 1.57; 95% CI: 1.13 to 2.18 and aHR: 2.53; 95% CI: 1.81 to 3.55, respectively). Of the 464 events, 371 (80%) led to outpatient care (IR: 45.6/100 CYs) and 164 (35%) to inpatient care (IR: 20.2/100 CYs). In adjusted analyses, outpatient care was significantly less frequent in children older than 10 years compared with children younger than 2 years (aHR: 0.49; 95% CI: 0.31 to 0.78) and in those living furthest from clinics compared with those living closest (aHR: 0.65; 95% CI: 0.47 to 0.90). Both inpatient and outpatient HCRU were negatively associated with cotrimoxazole prophylaxis. Despite ART, HIV-infected children still require substantial utilization of health care services.


A melodic contour repeatedly experienced by human near-term fetuses elicits a profound cardiac reaction one month after birth.
Human hearing develops progressively during the last trimester of gestation. Near-term fetuses can discriminate acoustic features, such as frequencies and spectra, and process complex auditory streams. Fetal and neonatal studies show that they can remember frequently recurring sounds. However, existing data can only show retention intervals up to several days after birth. Here we show that auditory memories can last at least six weeks. Experimental fetuses were given precisely controlled exposure to a descending piano melody twice daily during the 35(th), 36(th), and 37(th) weeks of gestation. Six weeks later we assessed the cardiac responses of 25 exposed infants and 25 naive control infants, while in quiet sleep, to the descending melody and to an ascending control piano melody. The melodies had precisely inverse contours, but similar spectra, identical duration, tempo and rhythm, thus, almost identical amplitude envelopes. All infants displayed a significant heart rate change. In exposed infants, the descending melody evoked a cardiac deceleration that was twice larger than the decelerations elicited by the ascending melody and by both melodies in control infants. Thus, 3-weeks of prenatal exposure to a specific melodic contour affects infants 'auditory processing' or perception, i.e., impacts the autonomic nervous system at least six weeks later, when infants are 1-month old. Our results extend the retention interval over which a prenatally acquired memory of a specific sound stream can be observed from 3-4 days to six weeks. The long-term memory for the descending melody is interpreted in terms of enduring neurophysiological tuning and its significance for the developmental psychobiology of attention and perception, including early speech perception, is discussed.


Ecological filtering by a dominant herb selects for shade tolerance in the tree seedling community of coastal dune forest.
The regeneration niche is commonly partitioned along a gradient from shade-tolerant to shade-intolerant species to explain plant community assembly in forests. We examined the shade tolerance of tree seedlings in a subtropical coastal forest to determine whether the ecological filtering effect of a dominant, synchronously monocarpic herb (Isoglossa woodii) selects for species at either end of the light response continuum during the herb's vegetative and reproductive phases. Photosynthetic characteristics of seedlings of 20 common tree species and the herb were measured. Seedlings were grown in the greenhouse at 12-14% irradiance, and their light compensation points measured using an open-flow gas exchange system. The light compensation points for the tree species were low, falling within a narrow range from 2.1 ± 0.8 μmol m(-2) s(-1) in Celtis africana to 6.4 ± 0.7 μmol m(-2) s(-1) in Allophylus natalensis, indicating general shade tolerance, consistent with a high and narrow range of apparent quantum yield among species (0.078 ± 0.002 mol CO(2) mol(-1) photon). Rates of dark respiration were significantly lower in a generalist pioneer species (Acacia karroo) than in a forest pioneer (C. africana), or in late successional phase forest species. We argue that the general shade tolerance, and phenotypic clustering of shade tolerance, in many tree species from several families in this system, is a result of ecological filtering by the prevailing low light levels beneath the I. woodii understorey, which excludes most light-demanding species from the seedling community.


Blood pressure variation in response to changing arm cuff height cannot be explained solely by the hydrostatic effect.
To challenge the widely accepted explanation of hydrostatic effect for blood pressure (BP) variation in response to arm elevation by testing the hypothesis that SBP and DBP measurements in the same individual vary differently with cuff height, and to evaluate the potential deviation of these measurements from the value predicted by the hydrostatic theory. Arm BP was measured in 37 individuals from the general population in the sitting position using a digital BP monitor. Measurements included nine consecutive BP readings at four cuff heights. The height dependence of BP was derived using reduced major axis regression. The variation in systolic and diastolic pressure had a highly linear correlation with cuff height (r = -0.90 and -0.93, respectively), with the systolic rate lower than the diastolic one by -0.13 ± 0.20 mmHg/cm (P = 0.0003) for all individuals. Systolic and diastolic rates were more negative in hypertensive individuals (P < 0.001 and P < 0.05, respectively). Significant deviation from the hydrostatic prediction of -0.77 mmHg/cm was observed in 30% of the individuals. This study assesses for the first time the inappropriateness of the hydrostatic theory as the sole explanation for the effect of gravity on BP. The phenomenon may be associated with mechanical properties of arteries in individuals known to have prognostic significance. The potential of the change in systolic and diastolic pressure with cuff height to be used as a novel type of clinical variable and vascular marker that can be determined by a simple test remains to be explored.


The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog.
The het-s locus of Podospora anserina is a heterokaryon incompatibility locus. The coexpression of the antagonistic het-s and het-S alleles triggers a lethal reaction that prevents the formation of viable heterokaryons. Strains that contain the het-s allele can display two different phenotypes, [Het-s] or [Het-s*], according to their reactivity in incompatibility. The detection in these phenotypically distinct strains of a protein expressed from the het-s gene indicates that the difference in reactivity depends on a posttranslational difference between two forms of the polypeptide encoded by the het-s gene. This posttranslational modification does not affect the electrophoretic mobility of the protein in SDS/PAGE. Several results suggest a similarity of behavior between the protein encoded by the het-s gene and prions. The [Het-s] character can propagate in [Het-s*] strains as an infectious agent, producing a [Het-s*] --> [Het-s] transition, independently of protein synthesis. Expression of the [Het-s] character requires a functional het-s gene. The protein present in [Het-s] strains is more resistant to proteinase K than that present in [Het-s*] mycelium. Furthermore, overexpression of the het-s gene increases the frequency of the transition from [Het-s*] to [Het-s]. We propose that this transition is the consequence of a self-propagating conformational modification of the protein mediated by the formation of complexes between the two different forms of the polypeptide.


Efficiency of extension of mismatched primer termini across from cisplatin and oxaliplatin adducts by human DNA polymerases beta and eta in vitro.
DNA polymerases beta and eta are among the few eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro. Our laboratory has previously established that both polymerases misincorporated dTTP with high frequency across from cisplatin- and oxaliplatin-GG adducts. This decrease in polymerase fidelity on platinum-damaged DNA could lead to in vivo mutations, if this base substitution were efficiently elongated. In this study, we performed a steady-state kinetic analysis of the steps required for fixation of dTTP misinsertion during translesion synthesis past cisplatin- and oxaliplatin-GG adducts by pol beta and pol eta. The efficiency of translesion synthesis by pol eta past Pt-GG adducts was very similar to that observed for this polymerase when the template contains thymine-thymine dimers. This finding suggested that pol eta could play a role in translesion synthesis past platinum-GG adducts in vivo. On the other hand, translesion synthesis past platinum-GG adducts by pol beta was much less efficient. Translesion synthesis by pol eta is likely to be predominantly error-free, since the probability of correct insertion and extension by pol eta was 1000-2000-fold greater than the probability of incorrect insertion and extension. Our results also indicated that for pol eta the frequency of misincorporation is the same across from the 3'G and the 5'G of the platinum-GG adducts for both cisplatin and oxaliplatin adducts. On the other hand, pol beta is more likely to misinsert at the 3'G of the adducts and misinsertion occurs at higher frequency for oxaliplatin-GG than for cisplatin-GG adducts.


Post-tetanic potentiation of response in monosynaptic reflex pathways of the spinal cord.
Following tetanic afferent stimulation of a monosynaptic reflex pathway, the transmission through that pathway of isolated reflex volleys is enhanced for some minutes. Post-tetanic potentiation is comparable in the monosynaptic reflex arcs of flexor and extensor muscles. The facilitator and inhibitor actions of monosynaptic reflex afferent fibers, as well as the transmitter action, are potentiated following tetanization. Little post-tetanic change attends reflex transmission through plurisynaptic reflex arcs. Various tests for excitability change made independently of the tetanized afferent fibers reveal none or a slight depression. Hence the potentiating influence of a tetanus is limited to subsequent action on the part of the recently tetanized fibers themselves. Increase in the size of the individual impulses comprising an afferent volley such as might occur during positive after-potential, would accommodate the requirement for a limited process and provide for increased synaptic action. The proposed association between post-tetanic potentiation and positive after-potential (i.e. hyperpolarization) is supported by the following lines of evidence:- 1. Changes in intensity and duration of potentiation with change in frequency and duration of tetanic stimulation are characteristic of, and parallel to, the changes of positive after-potential in similar circumstances. 2. Afferent impulses are increased following a tetanus, and in a fashion that parallels the course of monosynaptic reflex potentiation. Post-tetanic potentiation, as here described, and after-discharge, whatever may be its mechanism, are unrelated phenomena.


Quantifying training intensity distribution in a group of Norwegian professional soccer players.
This study was designed to quantify the daily distribution of training intensity in a group of professional soccer players in Norway based on three different methods of training intensity quantification. Fifteen male athletes (age, 24 ± 5 y) performed treadmill test to exhaustion to determine heart rate and VO2 corresponding to ventilatory thresholds (VT1, VT2), maximal oxygen consumption (VO2max) and maximal heart rate. VT1 and VT2 were used to delineate three intensity zones based on heart rate. During a 4 wk period in the preseason (N = 15), and two separate weeks late in the season (N = 11), all endurance and on-ball training sessions (preseason: N = 378, season: N= 78) were quantified using continuous heart rate registration and session rating of perceived exertion (sRPE). Three different methods were used to quantify the intensity distribution: time in zone, session goal and sRPE. Intensity distributions across all sessions were similar when based on session goal or by sRPE. However, intensity distribution based on heart rate cut-offs from standardized testing was significantly different (time in zone). Our findings suggest that quantifying training intensity by using heart rate based total time in zone is not valid for describing the effective training intensity in soccer. The results also suggest that the daily training intensity distribution in this representative group of high level Norwegian soccer players is organized after a pattern where about the same numbers of training sessions are performed in low lactate, lactate threshold, and high intensity training zones.


Estimating shipping emissions in the region of the Sea of Marmara, Turkey.
Ship emissions are significantly increasing globally and have remarkable impact on air quality on sea and land. These emissions contribute serious adverse health and environmental effects. Territorial waters, inland seas and ports are the regions most affected by ship emissions. As an inland sea the Sea of Marmara is an area that has too much ship traffic. Since the region of the Marmara is highly urbanized, emissions from ships affect human health and the overall environment. In this paper exhaust gas emissions from ships in the Sea of Marmara and the Turkish Straits are calculated by utilizing the data acquired in 2003. Main engine types, fuel types, operations types, navigation times and speeds of vessels are taken into consideration in the study. Total emissions from ships in the study area were estimated as 5,451,224 t y(-1) for CO(2), 111,039 t y(-1) for NO(x), 87,168 t y(-1) for SO(2), 20,281 t y(-1) for CO, 5801 t y(-1) for VOC, 4762 t y(-1) for PM. The shipping emissions in the region are equivalent to 11% of NO(x) 0.1% of CO and 0.12% of PM of the corresponding total emissions in Turkey. The shipping emissions in the area are 46% of NO(x), 25% of PM and 1.5% of CO of road traffic emissions in Turkey data between which and correspond to a higher level than aircraft emissions and rail emissions in Turkey.


Examination of AsmA and its effect on the assembly of Escherichia coli outer membrane proteins.
asmA mutations were isolated as extragenic suppressors of an OmpF assembly mutant, OmpF315. This suppressor locus produced a protein that was present in extremely low levels and could only be visualized by Western blotting in cells where AsmA expression was induced from a plasmid. Detailed fractionation analyses showed that AsmA localized with the inner membrane. Curiously, however, the mutant OmpF assembly step influenced by AsmA occurred in the outer membrane, perhaps indicating an indirect involvement of AsmA in the assembly of outer membrane proteins. Biochemical examination of the outer membrane showed that asmA null mutations reduce lipopolysaccharide (LPS) levels, thereby lowering the ratios of glycerolphospholipids to LPS and envelope proteins to LPS in the outer membrane. Despite these quantitative alterations, no apparent structural changes in LPS or major phospholipids were noted. Reduced LPS levels in asmA mutants indicate a possible role of AsmA in LPS biogenesis. Data presented in this study suggest that asmA-mediated OmpF assembly suppression may have been achieved by altering the outer membrane fluidity, thus making it more amenable for the assembly of mutant proteins.


The impact of rainfall and school break time policies on physical activity in 9-10 year old British children: a repeated measures study.
The weather may be a driver of seasonal patterns in children's physical activity (PA). A better understanding of the relationships between weather and PA may help increase children's PA. This study aims to examine the association between PA and rainfall in 9-10 year old children, and how it may be modified by school policies. 1794 participants in the SPEEDY study in Norfolk, UK recorded PA using ActiGraph accelerometers over up to six days in the summer term of 2007. Multilevel regression models were used to determine the day-by-day association between rainfall and minutes spent sedentary, in moderate-to-vigorous PA (MVPA), and average counts per minute (cpm) over the whole day (07:00-21:00) and the lunchtime period (12:00-14:00). School policies for break times in bad weather were fitted as interaction terms with rainfall. Relative to days with no rain, children spent 9.4 minutes (95%CI 7.0 to 11.9) fewer in MVPA, were sedentary for 13.6 minutes (8.8 to 18.4) more, and accumulated 85.9 cpm (66.2 to 105.5) fewer over the whole day on the wettest days. Children allowed to play outside in wet weather showed the lowest lunchtime PA levels on the wettest days, undertaking 9.8 minutes (6.2 to 13.5) fewer MVPA, 16.1 minutes (10.3 to 21.9) more sedentary, and accumulating 408.0 cpm (250.9 to 565.1) fewer than those allowed to be active indoors. Rainfall is negatively associated with PA in primary school children, but providing indoor physical activities in wet weather may help children maintain physical activity levels irrespective of rainfall.


Implementation of a pharmacist-led pharmacogenomics service for the Program of All-Inclusive Care for the Elderly (PHARM-GENOME-PACE).
To determine the feasibility of implementing a pharmacist-led pharmacogenomics (PGx) service for the Program of All-Inclusive Care for the Elderly (PACE). A national centralized pharmacy providing PGx services to community-based PACE centers. Individuals 55 years of age and older enrolled in PACE who underwent PGx testing as part of their medical care (n = 296). Pharmacist-led PGx testing, interpreting, and consulting. Implementation processes and roles were ascertained by reviewing policies and procedures for the PGx service and documented observations made by pharmacists providing the service. Genetic variants and drug-gene interactions (DGIs) were determined by interpretations of PGx test results. Types of recommendations provided by pharmacists were ascertained from PGx consultations. Prescribers' acceptance of recommendations were ascertained by documented responses or drug changes made after PGx consultations. Challenges to implementation included lack of systems interoperability, limited access to medical electronic health records, determining prescribers' responses, and knowledge and competency gaps in PGx. Pharmacist roles most essential to overcoming challenges were interpreting and applying PGx data, determining how to disseminate those data to prescribers, advocating for appropriate PGx testing, and educating about the application of test results to clinical practice. Participants frequently used drugs posing DGI risks, with the majority (73.6%) reporting more than 1 interaction. The overwhelming majority (89.0%) of pharmacists' recommendations to mitigate risks were accepted by referring prescribers. Implementing a pharmacist-led PGx service for PACE is feasible. Implementation of this service highlights the leadership role of pharmacists in moving PGx from research to practice.


A new method for constructing membership functions and fuzzy rules from training examples.
To extract knowledge from a set of numerical data and build up a rule-based system is an important research topic in knowledge acquisition and expert systems. In recent years, many fuzzy systems that automatically generate fuzzy rules from numerical data have been proposed. In this paper, we propose a new fuzzy learning algorithm based on the alpha-cuts of equivalence relations and the alpha-cuts of fuzzy sets to construct the membership functions of the input variables and the output variables of fuzzy rules and to induce the fuzzy rules from the numerical training data set. Based on the proposed fuzzy learning algorithm, we also implemented a program on a Pentium PC using the MATLAB development tool to deal with the Iris data classification problem. The experimental results show that the proposed fuzzy learning algorithm has a higher average classification ratio and can generate fewer rules than the existing algorithm.


[Comparative study of formation of the frontal cortex of the brain of monkeys and man in ontogenesis].
The development of the fields of the frontal zone (8, 3, 10, 11, 12) were compared in the pre- and postnatal periods oflife in the nacaque-rhesus and man. The cyto-mielcarchitectonical and guantitative methods wereused. The square surfaces of the above fields were measured, their per cent ratios to thesquare surface of all the cortex, new cortex and frontal zone were calculated. The work hasrevealed the following: 1. General regularities in the development of frontal zones in monkeysand man: a) shorter terms for the formation of philogenetically old fields-11, 12, 8 andlonger terms for the new ones-9 and 10:b) predominant development of the frontal zone at theexpense of progressive young fields 9 and 10: c) predominat formation of the frontal zone bothkinds of primates in the postnatal period. 2. The specific features for each field (the termsfor isolation of the fields, the rate and direction of their development). 3. Substantial difference: more rapid maturation of the frontal zone in macaques (by the 6th -12th months of life)and more prolonged one in humans-by 12 years. A considerable growth of philogenetically newstructures (fields 9 and 10) in the system of all the cortex and the frontal zone wasshown in man as compared with monkey. The experimental ontogentical material is interpreted.


Nicotinic receptor Alpha7 expression during tooth morphogenesis reveals functional pleiotropy.
The expression of nicotinic acetylcholine receptor (nAChR) subtype, alpha7, was investigated in the developing teeth of mice that were modified through homologous recombination to express a bi-cistronic IRES-driven tau-enhanced green fluorescent protein (GFP); alpha7GFP) or IRES-Cre (alpha7Cre). The expression of alpha7GFP was detected first in cells of the condensing mesenchyme at embryonic (E) day E13.5 where it intensifies through E14.5. This expression ends abruptly at E15.5, but was again observed in ameloblasts of incisors at E16.5 or molar ameloblasts by E17.5-E18.5. This expression remains detectable until molar enamel deposition is completed or throughout life as in the constantly erupting mouse incisors. The expression of alpha7GFP also identifies all stages of innervation of the tooth organ. Ablation of the alpha7-cell lineage using a conditional alpha7Cre×ROSA26-LoxP(diphtheria toxin A) strategy substantially reduced the mesenchyme and this corresponded with excessive epithelium overgrowth consistent with an instructive role by these cells during ectoderm patterning. However, alpha7knock-out (KO) mice exhibited normal tooth size and shape indicating that under normal conditions alpha7 expression is dispensable to this process. The function of ameloblasts in alpha7KO mice is altered relative to controls. High resolution micro-computed tomography analysis of adult mandibular incisors revealed enamel volume of the alpha7KO was significantly reduced and the organization of enamel rods was altered relative to controls. These results demonstrate distinct and varied spatiotemporal expression of alpha7 during tooth development, and they suggest that dysfunction of this receptor would have diverse impacts upon the adult organ.