Plasmid maintenance functions of the large virulence plasmid of Shigella flexneri.
The large virulence plasmid pMYSH6000 of Shigella flexneri contains a replicon and a plasmid maintenance stability determinant (Stb) on adjacent SalI fragments. The presence of a RepFIIA replicon on the SalI C fragment was confirmed, and the complete sequence of the adjacent SalI O fragment was determined. It shows homology to part of the transfer (tra) operon of the F plasmid. Stb stabilizes a partition-defective P1 miniplasmid in Escherichia coli. A 1.1-kb region containing a homolog of the F trbH gene was sufficient to confer stability. However, the trbH open reading frame could be interrupted without impairing stability. Deletion analysis implicated the involvement of two small open reading frames, STBORF1 and STBORF2, that fully overlap trbH in the opposite direction. These open reading frames are closely related to the vagC and vagD genes of the Salmonella dublin virulence plasmid and to open reading frame pairs in the F trbH region and in the chromosomes of Dichelobacter nodosus and Haemophilus influenzae. Stb appears to promote better-than-random distribution of plasmid copies and is a plasmid incompatibility determinant. The F homolog does not itself confer stability but exerts incompatibility against the activity of the Stb system. Stb is likely to encode either an active partition system or a postsegregational killing system. It shows little similarity to previously studied plasmid stability loci, but the genetic organization of STBORF1 and STBORF2 resembles that of postsegregational killing mechanisms.


Oxidative mechanisms utilized by human neutrophils to destroy Escherichia coli.
Serum-opsonized bacteria are efficiently ingested and killed by neutrophils within the phagocytic vacuole, where they are exposed to an array of reactive oxygen metabolites and toxic lysosomal components. Although bacteria may be destroyed by oxygen-independent mechanisms alone, many types of bacteria are not killed effectively unless they are attacked by oxygen metabolites. However, the apparent inability of extracellular scavengers, or inhibitors, of oxygen metabolites to gain access to the phagocytic vacuole makes this system difficult to evaluate. Therefore, we investigated the ability of neutrophils triggered with phorbol myristate acetate to destroy unopsonized E. coli in a serum-free model system. Neutrophils incubated with phorbol myristate acetate at a cell-to-bacteria ratio of 1:4 caused a greater than 95% reduction in colony-forming units (CFU) of E. coli in 60 min at 37 degrees C. Destruction of E. coli by the stimulated neutrophils was dependent on neutrophil number, stimuli concentration, and the incubation period. The neutrophil-mediated bactericidal effect was stimulated by superoxide dismutase, but was inhibited by catalase, azide, or compounds known to scavenge hypochlorous acid. Although stimulated neutrophils can generate long-lived endogenous N- chloroamines , these compounds did not play a direct role in destruction of E. coli in our model system. However, in the presence of exogenous iodide, endogenous N- chloroamines exerted a powerful bactericidal effect. Finally, neutrophils triggered with opsonized zymosan could also mediate E. coli destruction by a qualitatively similar process. Thus, we have demonstrated that neutrophils have the potential to utilize the myeloperoxidase system to generate bactericidal quantities of a species with characteristics similar to, if not identical with, hypochlorous acid.


Collagen induces maturation of human monocyte-derived dendritic cells by signaling through osteoclast-associated receptor.
Osteoclast-associated receptor (OSCAR) is widely expressed on human myeloid cells. Collagen types (Col)I, II, and III have been described as OSCAR ligands, and ColII peptides can induce costimulatory signaling in receptor activator for NF-κB-dependent osteoclastogenesis. In this study, we isolated collagen as an OSCAR-interacting protein from the membranes of murine osteoblasts. We have investigated a functional outcome of the OSCAR-collagen interaction in human monocyte-derived dendritic cells (DCs). OSCAR engagement by ColI/II-induced activation/maturation of DCs is characterized by upregulation of cell surface markers and secretion of cytokines. These collagen-matured DCs (Col-DCs) were efficient drivers of allogeneic and autologous naive T cell proliferation. The T cells expanded by Col-DCs secreted cytokines with no clear T cell polarization pattern. Global RNA profiling revealed that multiple proinflammatory mediators, including cytokines and cytokine receptors, components of the stable immune synapse (namely CD40, CD86, CD80, and ICAM-1), as well as components of TNF and TLR signaling, are transcriptional targets of OSCAR in DCs. Our findings indicate the existence of a novel pathway by which extracellular matrix proteins locally drive maturation of DCs during inflammatory conditions, for example, within synovial tissue of rheumatoid arthritis patients, where collagens become exposed during tissue remodeling and are thus accessible for interaction with infiltrating precursors of DCs.


[Aqueous humor outflow capacity after argon laser trabeculoplasty. Preliminary report].
In a prospective study of 44 eyes with open angle-glaucoma and 27 with pseudocapsular glaucoma, the aqueous humor outflow facility was controlled for up to 12 months following argon laser trabeculoplasty (ALT). The average increase in the facility of outflow, which was 70% in open-angle glaucoma, was 25% higher in pseudocapsular glaucoma. In successful ALT, this increase in outflow facility was established within the first 20 hours after coagulation and did not decrease during the following year. There were no major complications such as transitory elevations of intraocular pressure, hyphema, or severe uveitis; this fact is interpreted as a result of the authors' technique, in which only the light-pigmented trabecular meshwork is coagulated.


Hydrophobic organic compound (HOC) partitioning behaviour to municipal wastewater colloidal organic carbon.
The sorption behaviour of hydrophobic organic compounds (HOCs) 1,2,4,5-tetrachlor-obenzene (TeCB), pentachlorobenzene (PeCB) and hexachlorobenzene (HCB) to Aldrich humic acid (AHA) and municipal wastewater treatment plant (MWTP) influent colloidal organic carbon (COC) was investigated using the gas-stripping technique. Gas stripping assumptions of gas/water equilibrium and a constant volatilization rate were validated prior to calculation of partitioning parameters. The logKCOC coefficients determined for MWTP influent COC were 3.86, 3.89 and 3.19 for TeCB, PeCB and HCB, respectively. Due to the presence of COC, the mass transfer of TeCB, PeCB and HCB with the primary effluent to the secondary biological stage was predicted to increase 8.7%, 9.6% and 1.2%, respectively, based on the measured COC concentration and logKCOC values. The calculated increases in apparent solubility for TeCB, PeCB and HCB in the primary effluent were 14.4%, 22.0% and 6.5%, respectively. This partitioning did not follow the expected trend (TeCB < PeCB < HCB) based on hydrophobicity predicted by octanol/water partitioning. The trend observed differed from the current AHA standard and correlation-based trends derived from natural COCs. More experiments with other HOCs are needed to better understand and predict the magnitude and significance of MWTP influent COCs on the fate and transport of HOCs during the MWTP process.


Comparison of the efficacy of latanoprost versus dorzolamide/timolol fixed combination therapy in patients with pseudoexfoliative glaucoma according to glaucoma stage.
Only a few trials have compared the intraocular pressure-lowering effects of prostaglandin analogs to carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy in patients with pseudoexfoliative glaucoma. Furthermore, the influence of the glaucoma stage on the intraocular pressure-lowering effects of these drug types has not been studied. The purpose of this study was to compare the IOP-lowering efficacy of latanoprost, a prostaglandin analog versus dorzolamide/timolol fixed combination, a carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy, in patients with pseudoexfoliative glaucoma based on glaucoma stage. The data of 32 eyes (32 patients) diagnosed with uniocular pseudoexfoliative glaucoma and treated with topical latanoprost (Group 1) or dorzolamide/timolol fixed combination (Group 2) were retrospectively assessed. The groups were subdivided into early and moderate-advanced stages. Patients' demographics, baseline intraocular pressure, final intraocular pressure, and intraocular pressure difference (the difference between the baseline and final intraocular pressure) were determined from medical records and compared between groups and according to glaucoma stage. The mean drug use duration was 17.7 ± 13.5 months. No significant differences in mean baseline intraocular pressure, mean final intraocular pressure and mean intraocular pressure difference between Groups 1 and 2. In Group 2, the mean intraocular pressure difference was significantly greater in patients with early versus moderate-advanced stage glaucoma (p=0.015). The difference, however, was not detected in Group 1. The mean intraocular pressure difference in early-stage glaucoma was significantly greater in Group 2 versus 1 (p=0.033). Latanoprost and dorzolamide/timolol fixed combination are effective treatments for newly diagnosed pseudoexfoliative glaucoma. In early-stage pseudoexfoliative glaucoma, greater intraocular pressure reduction was noted with dorzolamide/timolol fixed combination than with latanoprost; thus, dorzolamide/timolol fixed combination should be considered when a significant decrease in intraocular pressure is desired in early-stage glaucoma.


Decreased density of amygdaloid parvalbumin-positive interneurons and behavioral changes in dystonic hamsters (Mesocricetus auratus).
The dtsz hamster represents a model of primary paroxysmal nonkinesiogenic dyskinesia in which dystonic episodes can be induced by stress and anxious stimuli. This disease is regarded as a basal ganglia disorder. In fact, a deficit of striatal interneurons could play a key role in the pathophysiology in dystonic hamsters. Because the involvement of limbic structures cannot be excluded so far, the density of parvalbumin-immunoreactive (PV+) interneurons was determined in the basolateral amygdala in the present study. Compared with nondystonic hamsters, the density of PV+ interneurons was moderately decreased in the dtsz mutant. The functional consequence of this finding was examined by behavioral analyses. Examinations in the elevated plus maze and in a modified open field failed to disclose an enhanced anxiety-related behavior in dtsz hamsters (Mesocricetus auratus). A lower acoustic startle response and a stronger habituation in mutant hamsters than in controls correlated with a decreased body weight. Interestingly, prepulse inhibition was absent in mutant hamsters. The latter finding suggests a disturbed sensorimotor gating that can be related to alterations in both the basal ganglia nuclei and in limbic structures.


Men born in 1913 followed to age 100 years.
To examine causes of death for men above 80 years of age, and health status in centenarians in a cohort of men followed from age 50 years. Factors of importance for survival were studied. A representative sample of men born in 1913 was first examined in 1963 and re-examined at ages 54, 60, 67, 75, 80 and 100 years. Of 973 selected men, 855 (88%) were examined at age 50, and 10 were alive at age 100.Twenty-seven percent lived until 80 years. Cardiovascular disease was the most common cause of death after this age. Dementia was recorded in two of ten men at age 100. Long survival was related to the mothers' high age at death, to non-smoking, high social class at age 50 and high maximum working capacity at age 54 years. At age 100, the seven examined men had low/normal blood pressure. Serum values of troponin T, N-terminal pro-brain natriuretic peptides and C-reactive protein were elevated, but echocardiographic findings were normal. Ten men experienced their 100th birthday. Survival was related to non-smoking, mothers' high age at death, high social class and previous high physical working capacity. Age-adjusted reference levels for laboratory tests are needed for centenarians.


Combining atomistic simulation and X-ray diffraction for the characterization of nanostructures: a case study on fivefold twinned nanowires.
Recent progress in achieving high degrees of monodispersity in chemical synthesis of complex nanostructures creates the unique situation in which individual nanostructures become representative for the whole ensemble. Under these conditions, atomistic simulations can play a completely new role in interpreting structural data obtained from averaging techniques. We apply this approach to fivefold twinned Ag nanowires for which the existence of an ambient-stable tetragonal phase in the nanowire core has been recently proposed. Quantitative comparison of experimental X-ray diffraction data with atomistic calculations unequivocally shows that the diffractograms can be fully explained by the complex strain state and defect structure of fivefold twinned Ag nanowires with fcc crystal structure. In addition, our approach enables rapid and accurate determination of wire diameters by a modified Scherrer analysis which uses a database generated by atomistic simulations.


The Tilburg Frailty Indicator (TFI): New Evidence for Its Validity.
The Tilburg Frailty Indicator (TFI) is a self-report user-friendly questionnaire for assessing multidimensional frailty among community-dwelling older people. The main aim of this study is to re-evaluate the validity of the TFI, both cross-sectionally and longitudinally, focusing on the predictive value of the total TFI and its physical, psychological, and social domains for adverse outcomes disability, indicators of healthcare utilization, and falls. The validity of the TFI was determined in a sample of 180 Dutch community-dwelling older people aged 70 years and older. The participants completed questionnaires including the TFI, the Groningen Activity Restriction Scale (GARS) for assessing disability, and questions with regard to health care utilization and falls in 2016 and again one year later. The physical and psychological domains of the TFI were significantly correlated as expected with adverse outcomes disability, many indicators of healthcare utilization, and falls. Regression analyses showed that physical frailty was mostly responsible for the effect of frailty on the adverse outcomes. The cross-sectional and longitudinal predictive validity of total frailty with respect to disability and receiving personal care was excellent, evidenced by Areas Under the Curves (AUCs) >0.8. In most cases, using the cut-off point 5 for total frailty ensured the best values for sensitivity and specificity. The present study provided new, additional evidence for the validity of the TFI for assessing frailty in Dutch community-dwelling older people aiming to prevent or delay adverse outcomes, including disability.


Developmental properties of the Hertwig's epithelial root sheath in mice.
Hertwig's epithelial root sheath (HERS) plays an important role in tooth root formation. In this study, we examined root formation of the first molar in mice, focusing on cell proliferation, cell death, cell migration, and the expression patterns of the signaling molecules, including glycoproteins and proteoglycans between PN8 and PN26. The number of HERS cells decreased during root formation, although HERS retained total length until PN15. The migration of HERS cells did not occur during root formation. Moreover, the immunopositive reaction of laminin beta-3 and syndecan-1 in HERS indicates that both cell adhesion and cell proliferation are essential for HERS development. Bmp-2, Bmp-4, and Msx-2 were expressed in HERS cells during root formation. We also developed an in vitro culture system for investigating the periodontium and suggest that this system provides an excellent vehicle for full exploration, and hence improved understanding, of the development and regeneration of the periodontium. Together, our results provide a comprehensive model describing the morphogenesis of early root development in vertebrates.


Passive immunization with monoclonal antibodies: effects on Haemaphysalis longicornis tick infestation of BALB/c mice.
Tick vaccine development plays an important role in current tick control strategies. Previously, we have produced three different isotypes of monoclonal antibodies (mAbs) which recognized a midgut protein of adult Haemaphysalis longicornis. These mAbs, typed as IgG1, 2a, and 2b, reacted with a 76 kDa surface protein of midgut cells. We speculated that the 76 kDa protein may be an unknown antigen for a tick vaccine and the three mAbs may work as probes to clone the protein. In this study, to test whether these three isotypes have anti-tick effects and if so which works more effectively, we conducted passive immunization in BALB/c mice with each of the mAbs, and infested the mice with adult ticks. All isotypes significantly reduced the number of hatched larvae, compared to controls, however, no differences in the magnitude of the reduction were observed among the three.


Impact of Preexisting Left Bundle Branch Block in Transcatheter Aortic Valve Replacement Recipients.
The impact of preexisting left bundle branch block (LBBB) in transcatheter aortic valve replacement (TAVR) recipients is unknown. The aim of this study was to determine the impact of preexisting LBBB on clinical outcomes after TAVR. This multicenter study evaluated 3404 TAVR candidates according to the presence or absence of LBBB on baseline ECG. TAVR complications and causes of death were defined according to Valve Academic Research Consortium-2 definitions. Follow-up outpatient visits or telephone interviews were conducted at 30 days, 12 months, and yearly thereafter. Echocardiography examinations were performed at baseline, at hospital discharge, and at 1-year follow-up. Preexisting LBBB was present in 398 patients (11.7%) and was associated with an increased risk of permanent pacemaker implantation (PPI; 21.1% versus 14.8%; adjusted odds ratio, 1.51; 95% CI, 1.12-2.04) but not death (7.3% versus 5.5%; adjusted odds ratio, 1.33; 95% CI, 0.84-2.12) at 30 days. At a mean follow-up of 22±21 months, there were no differences between patients with and without preexisting LBBB in overall mortality (adjusted hazard ratio, 0.94; 95% CI, 0.75-1.18) and cardiovascular mortality (adjusted hazard ratio, 0.90; 95% CI, 0.68-1.21). In a subanalysis of 2421 patients without PPI at 30 days and with complete follow-up about the PPI, preexisting LBBB was not associated with an increased risk of PPI or sudden cardiac death. Patients with preexisting LBBB had a lower left ventricular ejection fraction (LVEF) at baseline and at 1-year follow-up ( P <0.001 for both), but those with low LVEF exhibited a similar increase in LVEF over time after TAVR compared with patients with no preexisting LBBB ( P=0.327). Preexisting LBBB significantly increased the risk of early (but not late) PPI after TAVR, without any significant effect on overall mortality or cardiovascular mortality. Preexisting LBBB was associated with lower LVEF pre-TAVR but did not prevent an increase in LVEF post-TAVR similar to patients without LBBB.


Species differences in ligand interaction and activation of estrogen receptors in fish and human.
Estrogen receptor (ER) sequences vary between species and this suggests that there are differences in the ligand-specificity, leading to species-specific effects. This would indicate that it is not possible to generalize effects across species. In this study, we investigated the differences in activation potencies and binding affinities of ER´s alpha (α) and beta (β) in human, zebrafish and sea bream to elucidate species differences in response to estradiol, estrone, estriol and methyltestosterone. In vitro analysis showed that estradiol had the highest activity for all the ER´s except for human ERβ and seabream ERβ2. Alignment of the ligand binding domain and ligand binding pocket (LBP) residues of the three species showed that different residues were involved in the LBPs which led to differences in pocket volume, affected binding affinity and orientation of the ligands. By combining in silico and in vitro results, it was possible to identify the ligand specificities of ER´s. The results demonstrated that the human ER´s show lower resolution in ligand-dependent activation, suggesting higher promiscuity, than the zebrafish and seabream ER´s. These results show species-specificity of ER´s and suggest that species-specific differences must be taken into consideration when studying different exposure scenarios.


Role of light in the synthesis of nitrate reductase and nitrite reductase in rice seedlings.
1. In rice seedlings synthesis of methyl viologen-nitrite reductase was stimulated by light, as was that of NADH-nitrate oxidoreductase (EC 188.8.131.52). A small residual effect of light on the synthesis of the enzymes persisted in the dark for a short time. 2. In etiolated seedlings exposed to light and nitrate, a lag period of 3h was necessary before enzyme synthesis commenced, whereas in green seedlings kept in the dark for 36h, synthesis of both the enzymes started as soon as light and nitrate were provided. 3. Experiments with cycloheximide suggested that fresh protein synthesis in light was necessary for formation of active enzymes. Mere activation by light of inactive enzymes or their precursors, was not involved. 4. In green seedlings synthesis of nitrite reductase was more sensitive to chloramphenicol than that of nitrate reductase. In chloramphenicol-treated etiolated seedlings, however, synthesis of both the enzymes was inhibited to the same extent on subsequent light-treatment. 5. A close correlation was observed between inhibition of the Hill reaction by 3-(3,4-dichlorophenyl)-1,1-dimethylurea and simazin [2-chloro-4,6-bis(ethylamino)-s-triazine] (at high concentration) and the inhibition of enzyme synthesis. At lower concentrations, however, simazin stimulated nitrate reductase. 6. In a single leaf synthesis of enzymes was observed only in portions exposed to light, whereas little activity was present in the dark covered part. 7. CO(2) deprivation severely inhibited the synthesis of enzymes in the light. Sucrose could not reverse this effect. 8. In excised embryos cultured in synthetic media containing sucrose, light was also essential for enzyme formation. 9. It is suggested that redox changes taking place in the green tissues as a result of the Hill reaction create conditions favourable for the induced synthesis of nitrate reductase and nitrite reductase.


[The dynamics of individual preference in the probability and value of reinforcement in the development of experimental neurosis].
After single and repeated negative emotiogenic (neuroticizing) influences in phlegmatics and cholerics in a situation with different probability and value of reinforcement a change of behaviour strategy takes place--from the preference of a reinforcement of higher probability but worse quality to that of low probability but valuable. Strategy of behaviour of sanguinics and melancholics remains unchanged with the preference of a reinforcement of low probability but better quality. The greatest sensibility to negative emotiogenic influence (a conflict situation) was established in phlegmatics and the lowest sensibility--in sanguinics. The obtained data are discussed from the positions of P. V. Simonov's concept on the four brain macrostructures (the hippocampus, amygdala, hypothalamus, and the frontal cortex) in the aspect of significance of the level of their functioning and interaction for the pathogenesis of neuroses.


Dual Photo-Responsive Diphenylacetylene Enables PET In-Situ Upcycling with Reverse Enhanced UV-Resistance and Strength.
A novel in situ chemical upcycling strategy for plastic waste is proposed by the customized diphenylacetylene monomer with dual photo-response. That is, diphenylacetylene reactive monomers are in situ inserted into the macromolecular chain of polyethylene terephthalate (PET) plastics/fibers through one-pot transesterification of slight-depolymerization and re-polymerization. On the one hand, the diphenylacetylene group absorbs short-wave high-energy UV rays and then releases long-wave low-energy harmless fluorescence. On the other hand, the UV-induced photo-crosslinking reaction among diphenylacetylene groups produces extended π-conjugated structure, resulting in a red-shift (due to decreased HOMO-LUMO separation) in the UV absorption band and locked crosslink points between PET chains. Therefore, with increasing UV exposure time, the upcycled PET plastics exhibit reverse enhanced UV resistance and mechanical strength (superior to original performance), instead of serious UV-photodegradation and damaged performance. This upcycling strategy at oligomer-scale not only provides a new idea for traditional plastic recycling, but also solves the common problem of gradual degradation of polymer performance during use.


Eccrine-Centric Melanocytic Nevus.
Benign melanocytic neoplasms present with a diverse array of well-known histopathologic patterns. It is imperative to recognize the benign patterns to render accurate diagnoses. We describe here an interesting and hitherto not described low-power architectural pattern of a benign melanocytic lesion: eccrine-centric melanocytic nevus. The patient was a 50-year-old African American woman who noticed a new mole on her foot that began as a dark speck but quickly grew larger. The lesion was excised to exclude the possibility of melanoma. Upon review of the specimen, the lesion was noted to demonstrate a distinctive pattern consistent with a melanocytic nevus of possible congenital onset. Remarkably, the ducts of eccrine glands were increased in density and the nests of melanocytes were found solely in a peri-eccrine distribution without melanocytes in any other locations (ie, interstitial, perifollicular). Additionally, all melanocytes in the nevus were rather heavily pigmented. Although this pattern demonstrated no atypical features that would cause one to consider it malignant to the trained eye, this presentation could implicate a metastatic disease (well-delineated nests in the dermis without concomitant interstitial component) and it is important to recognize.


[Risk assessment indexes for shellfish poisoning outbreak caused by red tide].
To establish the indexes and weights of risk assessment of shellfish poisoning outbreak caused by red tide. The risk assessment indexes were developed with the methods of literature review, brainstorm and expert consultation, and the weights of indexes were calculated by the method of analytic hierarchy process. The established indexes contained the risk possibility, impacts of public health, population vulnerability and resilience. The relative risk indexes(integrated risk indexes) of different shellfish poisoning were computed by combining hierarchy process and TOPSIS methods. Moreover, the weights of indexes were further used to generate absolute risk values by multiplying indexes. Four primary indexes and 17 secondary indexes were identified for risk assessment of shellfish poisoning outbreak. Of 17 secondary indexes, the knowing rate of shellfish poisoning, medical accessibility, the number of people being affected, laboratory testing capacity and the habits of eating seafood of local residents had relatively large weights (0.0876, 0.0840, 0.0716, 0.0703 and 0.0644, respectively), which accounted for nearly 38% of the total weight. All consistency ratio (CR) were less than 0.1. The index system was applied in Cangnan county of Zhejiang province. The results showed the relative risk indexes of paralytic shellfish poisoning (PSP), diarrhetic shellfish poisoning (DSP), neurotoxic shellfish poisoning (NSP) and amnesic shellfish poisoning (ASP) were 0.4526, 0.7116, 0.1657 and 0.2884, and the absolute risk values were 0.2542, 0.2668, 0.1907 and 0.2184, respectively. The risk orders of the 4 kinds of shellfish poisoning sorted by relative risk indexes and absolute risk values were consistent. The indexes and weights of risk assessment of shellfish poisoning outbreak caused by red tide are established, which can provide scientific advice for prevention and control of shellfish poisoning outbreak.


[Dimeric and monomeric forms of dinitrosyl iron complexes with thiol-containing ligands: physico-chemical properties and vasodilator activity].
When studying the vasodilator activity of dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO donors, it should be taken into consideration that these complexes depending on the content of thiols in the environment can occur in either form that differ by their EPR, gamma-resonance and optical characteristics and also by their vasodilator effect on isolated blood vessels. The more stable diamagnetic form appears at the ratio Fe2+:RS(-)-1:2. It reversibly dissociates to the monomeric paramagnetic form [(RS-)2Fe+(NO+)2] on increasing the thiol content to the level 20 times and more exceeding the quantity of iron. It is suggested that stabilization of the dimeric form is provided by formation of RS(-)-NO+ bonds between monomeric components of the dimer. This process is favored by a corresponding orientation of the monomers relative to each other. A high stability of the DNIC dimeric form correlates with more prolonged vasodilator effect of this complex as an NO source. Replacement of cysteine by reduced glutathione in dimeric and monomeric forms of DNIC increases both stability of the complexes and the duration of their vasodilator effect.


Infectious disease transmission and infection-dependent matching.
This paper uses commonly available prevalence estimates to bound future incidence. The bounds rely on restricting the fraction of contacts between individuals of different infection statuses. It is argued that these bounds can be further tightened by restrictions of economic models of infectious disease that imply that uninfected individuals have larger incentives to avoid matching with infected individuals than do the infected individuals themselves. This implies that incidence predictions from canonical models of infectious disease are worst-case upper bounds, with the degree to which they overestimate new cases being monotonically related to this type of infection-dependent matching. Evidence in support of the economic type of infection-dependent matching is presented, by using data on the joint distribution of partners' HIV statuses in a random sample of couples from San Francisco in 1988-1989.


July Phenomenon Impacts Efficiency of Emergency Care.
The "July effect" describes the period in which new interns begin learning patient care while senior residents take on additional responsibility in an academic hospital setting. The annual change in staffing creates inefficiencies in patient care, which may negatively impact quality of care. Our objective was to evaluate the impact of the annual resident turnover on emergency department (ED) efficiency in a teaching hospital. This was an institutional review board-approved retrospective chart review spanning two academic years analyzing 79,921 records. We grouped July and August into the period of least experience (PLE) and May and June into the period of most experience (PME). Outcomes included faculty and resident productivity, ED door-to-doctor time, and time to disposition. Patients were evaluated by 117 emergency residents and 73 emergency faculty. We excluded patient records for 35 off-service residents. Residents saw 15.8% more patients in the PME compared to the PLE (p<0.0001). The residents' average door-to-doctor time during the PLE was 45.63 minutes (standard deviation [SD] 33.01, median 36) compared to 34.69 minutes (SD 25.22, median 28) during the PME, with a decrease in time by 21.3% (p=0.0203). The residents' average time to disposition during the PLE was 304.6 minutes (SD 308, median 217) compared to 269.0 minutes (SD 282, median 194) during the PME, decreasing by 12.4% (p=0.0001). Residents had an average ED length of stay for discharged patients of 358.5 minutes (SD 374.6, median 238) during the PLE compared to 309.9 minutes (SD 346.4, median 209) during the PME, decreasing 13.7% for discharged patients (p=0.0017). Annual turnover of resident staffing has a significant impact on common ED efficiency metrics. EDs should consider interventions to mitigate the impact of these expected inefficiencies.


The Effect of Load Placement on the Power Production Characteristics of Three Lower Extremity Jumping Exercises.
The purpose of this study was to compare the power production characteristics of the jump squat (JS), hexagonal barbell jump (HEXJ), and jump shrug (JShrug) across a spectrum of relative loads. Fifteen resistance-trained men completed three testing sessions where they performed repetitions of either the JS, HEXJ, or JShrug at body mass (BM) or with 20, 40, 60, 80, or 100% of their BM. Relative peak power (PPRel), relative force at PP (FPP), and velocity at PP (VPP) were compared between exercises and loads. In addition, power-time curves at each load were compared between exercises. Load-averaged HEXJ and JShrug PPRel were statistically greater than the JS (both p < 0.01), while no difference existed between the HEXJ and the JShrug (p = 1.000). Load-averaged JShrug FPP was statistically greater than both the JS and the HEXJ (both p < 0.001), while no statistical difference existed between the JS and the HEXJ (p = 0.111). Load-averaged JS and HEXJ VPP were statistically greater than the JShrug (both p < 0.01). In addition, HEXJ VPP was statistically greater than the JS (p = 0.009). PPRel was maximized at 40, 40, and 20% BM for the JS, HEXJ, and JShrug, respectively. The JShrug possessed statistically different power-time characteristics compared to both the JS and the HEXJ during the countermovement and propulsion phases. The HEXJ and the JShrug appear to be superior exercises for PPRel compared to the JS. The HEXJ may be considered a more velocity-dominant exercise, while the JShrug may be a more force-dominant one.


Short stature, mental retardation, and hypoparathyroidism: a new syndrome.
Eight children (four boys and four girls) with extreme failure to thrive, dysmorphic features, developmental delay, hypoparathyroidism, and abnormal skeletal survey were studied. They were the products of seven consanguinous marriages, two of the patients being brothers. In the remaining six families, a further four children had affected siblings who had died in infancy. When assessed the children were aged 0.47-12.8 years; SD scores were less than -2 for height, weight, and head circumference in all patients. The children had identical facies with deep set eyes, depressed nasal bridge with beaked nose, long philtrum, thin upper lip, micrognathia, and large floppy earlobes. They were all developmentally retarded. The following abnormalities were found on investigation: hypocalcaemia in all (of whom six of seven had hypoparathyroidism), medullary stenosis and other skeletal survey defects in seven of the eight children, and reduced numbers of T cell subsets in four of four tested. We believe that these children represent a new, as yet undescribed genetically determined syndrome.


Perioperative management of obstructive sleep apnea: a systematic review.
Obstructive sleep apnea (OSA) is the leading sleep disordered breathing condition, with a prevalence rate of moderate to severe OSA of approximately 10-17% in the general population. We performed an Ovid-Medline search of all articles published up to August 2016. We included all articles providing updated evidence on epidemiology, pathophysiologic mechanisms and perioperative interventions. OSA is associated with a number of comorbidities and increased perioperative risks. Although in-laboratory polysomnography represents the gold-standard for diagnosis of OSA, it is costly and time-consuming. Anesthesiologists may screen patients for OSA through one of the available questionnaires, of which the snoring, tiredness, observed apnea, high blood pressure (STOP)-Body Mass Index, age, neck circumference and gender (Bang), STOP-bang questionnaire is the most externally validated. Although its sensitivity for the identification of mild OSA patients is 83.6%, its specificity is only 56.4%. OSA patients are associated with a higher risk of both difficult ventilation and intubation. However, practice guidelines refer to available guidelines for difficult airway management. Perioperative continuous positive airway pressure use may be of benefit since it has been reported to be associated with a reduction of both respiratory and cardiovascular complications and symptom relief. When feasible, regional anesthesia techniques and a multimodal analgesia approach should be adopted to reduce intraoperative and postoperative exposure to opioids. Preoperative screening of OSA patients is of relevance given the increased perioperative morbidity of these patients. Further studies are needed to provide conclusive data on which perioperative interventions are most effective at reducing this risk.


Change Blindness Is Influenced by Both Contrast Energy and Subjective Importance within Local Regions of the Image.
Our visual system receives an enormous amount of information, but not all information is retained. This is exemplified by the fact that subjects fail to detect large changes in a visual scene, i.e., change-blindness. Current theories propose that our ability to detect these changes is influenced by the gist or interpretation of an image. On the other hand, stimulus-driven image features such as contrast energy dominate the representation in early visual cortex (De Valois and De Valois, 1988; Boynton et al., 1999; Olman et al., 2004; Mante and Carandini, 2005; Dumoulin et al., 2008). Here we investigated whether contrast energy contributes to our ability to detect changes within a visual scene. We compared the ability to detect changes in contrast energy together with changes to a measure of the interpretation of an image. We used subjective important aspects of the image as a measure of the interpretation of an image. We measured reaction times while manipulating the contrast energy and subjective important properties using the change blindness paradigm. Our results suggest that our ability to detect changes in a visual scene is not only influenced by the subjective importance, but also by contrast energy. Also, we find that contrast energy and subjective importance interact. We speculate that contrast energy and subjective important properties are not independently represented in the visual system. Thus, our results suggest that the information that is retained of a visual scene is both influenced by stimulus-driven information as well as the interpretation of a scene.


Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations.
Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.


Effect of incidence angle on laser scanner intensity and surface data.
We present a comprehensive experimental set of data on the dependence of the laser intensity on the angle of incidence to the target surface. The measurements have been performed in the laboratory for samples with a Nd:YAG laser and terrestrial laser scanner. The brightness scale data were also compared with data acquired by airborne laser scanning (ALS). The incidence angle effect is evident for all the targets. The effect is significant for incidence angles >20 degrees, and stronger for bright targets. However, effects due to some of the other surface properties, such as roughness, were also detected. We also found a set of gravel samples for which the incidence angle effect was minor even up to 40 degrees . The data provide an important reference for the interpretation and applications, e.g., full-waveform data processing of a laser scanner and ALS intensity calibration.


Norfloxacin binds to human fecal material.
Earlier studies have reported very high (120 to 2,700 mg/kg) concentrations of norfloxacin in feces after therapeutic doses. MICs for fecal microorganisms are with few exceptions far below these levels. Nevertheless, clinical investigations show that the main part of the aerobic gram-positive and the anaerobic microflora remains unaffected after norfloxacin administration. In this study, the binding of [14C]norfloxacin to fecal material was analyzed. The binding of a group of nonlabeled quinolones to feces and the interactions between Enterococcus faecium, Bacteroides fragilis, and norfloxacin were also investigated. The results showed that norfloxacin has the ability to bind to feces. The specific binding was reversible, saturated after 90 min of incubation at 37 degrees C, and increased linearly with fecal concentration. Scatchard plots and nonlinear regression computer analyses revealed two different binding classes. The primary specific binding had a dissociation constant (KD) of 1.0 microM and a maximal binding capacity (Bmax) of 0.12 mumol/g of feces. The KD and Bmax of the secondary, more unspecific binding were 450 microM and 11.8 mumol/g of feces, respectively. The binding of unlabeled ciprofloxacin, enoxacin, ofloxacin, pefloxacin, and norfloxacin to feces was comparable to that of [14C]norfloxacin. The results of norfloxacin binding to suspensions of B. fragilis suggested that the main part of the binding is to the bacterial fraction of feces. In the presence of 8.0 g (dry weight) of B. fragilis per liter, the MBC of norfloxacin for E. faecium increased from 8 to 256 micrograms/ml. The finding of the present study indicated that binding of norfloxacin to feces may explain the paradox of high fecal concentrations of norfloxacin versus the actual effect on the normal gastrointestinal microflora.


The pluripotency rheostat Nanog functions as a dimer.
The defining activity of the homeodomain protein Nanog is the ability to confer cytokine-independent self-renewal upon ES (embryonic stem) cells in which it is overexpressed. However, the biochemical basis by which Nanog achieves this function remains unknown. In the present study, we show that Nanog dimerizes through a functionally critical domain. Co-immunoprecipitation of Nanog molecules tagged with distinct epitopes demonstrates that Nanog self-associates through a region in which every fifth residue is tryptophan. In vitro binding experiments establish that this region participates directly in self-association. Moreover, analytical ultracentrifugation indicates that, in solution, Nanog is in equilibrium between monomeric and dimeric forms with a K(d) of 3 muM. The functional importance of Nanog dimerization is established by ES cell colony-forming assays in which deletion of the tryptophan-repeat region eliminates the capacity of Nanog to direct LIF (leukaemia inhibitory factor)-independent self-renewal.


Molecular Insights into the MLCK Activation by CaM.
Calmodulin (CaM) is a universal regulatory protein that modulates numerous cellular processes by using calcium (Ca2+) as the signal. In smooth muscle cells (SMC), one major target of CaM is myosin light chain kinase (MLCK), a kinase that phosphorylates the myosin regulatory light chain and thereby regulates cell contraction. In the absence of CaM, MLCK remains inhibited by its autoinhibitory domain (AID). While it is well established that CaM activates MLCK, the molecular interactions between these two proteins remain elusive due to the lack of structural data. In this work, we constructed a molecular model of mammalian CaM (mCaM) in complex with MLCK leveraging AlphaFold, published biochemical data, and protein-protein docking. The model, along with a strategic set of CaM mutants including a inhibitory variant soybean CaM isoform 4 (sCaM-4), was subject to molecular dynamics (MD) simulations. Using principal component analysis (PCA), we mapped out the transition path for the removal of the AID from the MLCK kinase domain to provide molecular basis of MLCK activation. Additionally, we established MLCK conformations that correspond to the active and inactive states of the kinase. We showed that mCaM and sCaM-4 cause MLCK to undergo the transition to the active and inactive states, respectively. Using two structural metrics, we computed the probabilities of MLCK activation by different CaM variants, which were in good agreement with the experimental data. Distributions along these metrics revealed that different inhibitory CaM variants impair MLCK activation through unique mechanisms. We finally identified molecular contacts that contribute to the MLCK activation by CaM. Overall, we report a de novo molecular model of CaM-MLCK that provides insights into the molecular mechanism of MLCK activation by CaM. The mechanism requires effective removal of the AID while preserving an active configuration of the kinase domain. This mechanism may be shared by other MLCK isoforms and potentially other structurally similar kinases with CaM-mediated regulatory domains.


Evaluation of the use of an autologous platelet-rich fibrin membrane to enhance tendon healing in dogs.
To examine effects of an autologous platelet-rich fibrin (PRF) membrane for enhancing healing of a defect of the patellar tendon (PT) in dogs. 8 adult dogs. Defects were created in the central third of the PT in both hind limbs of each dog. An autologous PRF membrane was implanted in 1 defect/dog, and the contralateral defect was left empty. Dogs (n = 4/time period) were euthanized at 4 and 8 weeks after surgery, and tendon healing was assessed grossly and histologically via a semiquantitative scoring system. Cross-sectional area of the PTs was also compared. Both treated and control defects were filled with repair tissue by 4 weeks. There was no significant difference in the histologic quality of the repair tissue between control and PRF membrane-treated defects at either time point. At both time points, the cross-sectional area of PRF membrane-treated tendons was significantly greater (at least 2.5-fold as great), compared with that of sham-treated tendons. At 4 weeks, the repair tissue consisted of disorganized proliferative fibrovascular tissue originating predominantly from the fat pad. By 8 weeks, the tissue was less cellular and slightly more organized in both groups. A PRF membrane did not enhance the rate or quality of tendon healing in PT defects. However, it did increase the amount of repair tissue within and surrounding the defect. These results suggested that a PRF membrane may not be indicated for augmenting the repair of acutely injured tendons that are otherwise healthy.


Communicating Recommendations in Public Health Emergencies: The Role of Public Health Authorities.
Adherence to public health recommendations is critical for public safety and well-being. Effective and appropriate communication plays an important role in whether populations trust government and public health authorities, and the extent to which people follow public health recommendations. Poor trust in communication from public health authorities can pose significant challenges for mitigating public health emergencies and maintaining health security. This study aimed to explore the importance of trust in and understanding of communication from public health authorities in improving adherence to public health recommendations, and how that communication can be improved to develop and maintain public trust, particularly in the context of public health emergencies. To understand which factors are important for public trust in communication from public health authorities, we conducted in-depth interviews (n = 25) with a racially and demographically diverse group of individuals living in Baltimore. We found that communication source and communication transparency, such as timeliness, completeness, and clarity of information, were critical constructs of trust in communication from public health authorities. We also found that many participants misunderstood the flow of information from public health authorities to news media, and many were unaware that public health authorities provide the most reliable source of health information and recommendations during a public health emergency. To ensure adherence to public health recommendations, the public needs to trust that public health authorities are providing accurate, practical, and prudent recommendations. Drawing on these results, we provide several recommendations for developing and optimizing communication from various public health authorities.


Kinetic resolution of N-aryl β-amino alcohols via asymmetric aminations of anilines.
An efficient kinetic resolution of N-aryl β-amino alcohols has been developed via asymmetric para-aminations of anilines with azodicarboxylates enabled by chiral phosphoric acid catalysis. Broad substrate scope and high kinetic resolution performances were afforded with this method. Control experiments supported the critical roles of the NH and OH group in these reactions.


Irreversible gene repression model for control of development.
As the pluripotent cells of early embryos differentiate, each progressively loses the potency to develop into several phenotypes. Ultimately, each cell becomes irreversibly restricted to the expression of a single phenotype. Although in many instances details regarding those restriction events are well known, there is little information concerning the nature of the gene transcription changes involved. A model that accounts for the diminution of developmental potential as resulting from progressive, irreversible repression of previously active genes is presented. A scheme of progressive gene repression, rather than selective gene activation, is most consistent with observations from experimental embryology as well as from more recent biochemical experimentation.


Inhibitors of 17alpha-hydroxylase/17,20-lyase (CYP17): potential agents for the treatment of prostate cancer.
Prostate cancer (PCa) is now the most prevalent cancer in men in the U.S.A. and Europe. At present the major treatment options include surgical or medical castration. These strategies depend on the abolition of the production of testosterone by the testes. However, as these procedures do not affect adrenal androgen production, they are frequently combined with androgen receptor antagonist to block their action. Inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17alpha-hydroxylase/17,20-lyase (hereafter referred to as CYP17 ) could prevent androgen biosynthesis from both sources. Thus total blockade of androgen production by CYP17 inhibitors may provide effective treatment of prostate cancer patients. Indeed, this strategy is now an area of intense interest within research institutions and the pharmaceutical industry. This review highlights development in the design and evaluation of both steroidal and non-steroidal CYP17 inhibitors since 1965. Major emphasis is given to the potent CYP17 inhibitors and those which may show clinical promise. The review could function as a comprehensive working reference of research accomplishment in the field and what problems remain to be tackled in the future.


A loss-of-function RNA interference screen for molecular targets in cancer.
The pursuit of novel therapeutic agents in cancer relies on the identification and validation of molecular targets. Hallmarks of cancer include self-sufficiency in growth signals and evasion from apoptosis; genes that regulate these processes may be optimal for therapeutic attack. Here we describe a loss-of-function screen for genes required for the proliferation and survival of cancer cells using an RNA interference library. We used a doxycycline-inducible retroviral vector for the expression of small hairpin RNAs (shRNAs) to construct a library targeting 2,500 human genes. We used retroviral pools from this library to infect cell lines representing two distinct molecular subgroups of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like DLBCL and germinal centre B-cell-like DLBCL. Each vector was engineered to contain a unique 60-base-pair 'bar code', allowing the abundance of an individual shRNA vector within a population of transduced cells to be measured using microarrays of the bar-code sequences. We observed that a subset of shRNA vectors was depleted from the transduced cells after three weeks in culture only if shRNA expression was induced. In activated B-cell-like DLBCL cells, but not germinal centre B-cell-like DLBCL cells, shRNAs targeting the NF-kappaB pathway were depleted, in keeping with the essential role of this pathway in the survival of activated B-cell-like DLBCL. This screen uncovered CARD11 as a key upstream signalling component responsible for the constitutive IkappaB kinase activity in activated B-cell-like DLBCL. The methodology that we describe can be used to establish a functional taxonomy of cancer and help reveal new classes of therapeutic targets distinct from known oncogenes.


Barriers and facilitators to care-seeking among survivors of gender-based violence in the Dadaab refugee complex.
In humanitarian settings, timely access to care is essential for survivors of gender-based violence (GBV). Despite the existence of GBV support services, challenges still exist in maximising benefits for survivors. This study aimed to understand the characteristics of violence against women and explore barriers and facilitators to care-seeking for GBV by women in two camps within the Dadaab refugee complex in Kenya. A mixed-methods design was used to study women accessing comprehensive GBV services between February 2016 and February 2017. Women were recruited into a cohort study (n = 209) and some purposively selected for qualitative in-depth interviews (n = 34). Survivor characteristics were descriptively analysed from baseline measures, and interview data thematically assessed. A majority of women were Muslim, of Somali origin, had been residents in the camp for more than five years, with little or no formal education, and meagre or no monthly income. From the survey, 60.3% and 66.7% of women had experienced non-partner violence or intimate partner violence in their lifetime respectively. Facilitators to accessing GBV services by survivors included awareness of GBV services and self-perceived high severity of acts of violence. Barriers included stigma by family and the community, fear of further violence from perpetrators, feelings of helplessness and insecurity, and being denied entry to service provision premises by guards. Women in the Dadaab refugee camps face violence from intimate partners, family, and other refugees. There is an urgent need to address drivers of GBV and the barriers to disclosure and access to services for all survivors of GBV.


Bacterial grazing by planktonic lake algae.
Six common species of lake algae were found to ingest bacteria. The ingestion rates measured were of the same magnitude as those recorded for marine microflagellates totally dependent on external sources of carbon. A large biomass of Dinobryon species removed more bacteria from the water column of a lake than crustaceans, rotifers, and ciliates combined.


Characterization of the enzymatic defect in late-onset muscle phosphofructokinase deficiency. New subtype of glycogen storage disease type VII.
Human phosphofructokinase (PFK) exists in tetrameric isozymic forms, at least in vitro. Muscle and liver contain homotetramers M4 and L4, respectively, whereas red cells contain five isozymes composed of M (muscle) and L (liver) type subunits, i.e., M4, M3L, M2L2, and ML3, and L4. Homozygous deficiency of muscle PFK results in the classic glycogen storage disease type VII characterized by exertional myopathy and hemolytic syndrome beginning in early childhood. The genetic lesion results in a total and partial loss of muscle and red cell PFK, respectively. Characteristically, the residual red cell PFK from the patients consists of isolated L4 isozyme; the M-containing hybrid isozymes are completely absent. In this study, we investigated an 80-yr-old man who presented with a 10-yr history of progressive weakness of the lower limbs as the only symptom. The residual red cell PFK showed the presence of a few M-containing isozymes in addition to the predominant L4 species, indicating that the genetic lesion is a "leaky" mutation of the gene coding for the M subunit. The presence of a small amount of enzyme activity in the muscle may account for the atypical myopathy in this patient.


Codon-level co-occurrences of germline variants and somatic mutations in cancer are rare but often lead to incorrect variant annotation and underestimated impact prediction.
Cancer cells explore a broad mutational landscape, bringing the possibility that tumor-specific somatic mutations could fall in the same codons as germline SNVs and leverage their presence to produce substitutions with a larger impact on protein function. While multiple, temporally consecutive mutations to the same codon have in the past been detected in the germline, this phenomenon has not yet been explored in the context of germline-somatic variant co-occurrences during cancer development. We examined germline context at somatic mutation sites for 1395 patients across four cancer cohorts (breast, skin, colon, and head and neck) and found 392 codon-level co-occurrences between germline and somatic variants, including over a dozen in well-known cancer genes. We found that for the majority of these co-occurrence events, traditional somatic calling led to an inaccurate representation of the protein site and a significantly lower predicted impact on protein fitness. We conclude that these events often lead to imprecise annotation of somatic variants but do not appear to be a frequent source of driver events during cancer development.


Serious adverse events associated with vasopressin and norepinephrine infusion in septic shock.
The frequency, risk factors, and mortality rates of serious adverse events associated with the use of vasopressin and norepinephrine are not clear. The objectives of this study were to determine frequency, risk factors (including candidate gene polymorphisms), and outcomes of serious adverse events in septic shock patients. Retrospective cohort study using multicenter discovery and single-center validation cohorts. ICUs at academic teaching centers. Five hundred ninety-seven patients with septic shock in discovery (Vasopressin and Septic Shock trial) and 533 patients in validation (St. Paul's Hospital) cohorts. Vasopressin and norepinephrine for septic shock. The primary outcome variable was 90-day mortality rates of patients with and without serious adverse events. Secondary outcome variables were the association between vasopressor genotype pathway polymorphisms, plasma vasopressin levels, and serious adverse events. Plasma vasopressin concentrations were measured at baseline, 6 hours, 24 hours, 72 hours, and 7 days after vasopressor infusion. Patients with septic shock were genotyped for 268 vasopressor pathway tag single-nucleotide polymorphisms. Serious adverse events occurred in 10.5% and 9.7% of patients in Vasopressin and Septic Shock trial and St. Paul's Hospital cohorts, respectively. Patients who had serious adverse events had higher mortality (p < 0.01) than patients without serious adverse events (adjusted for age, serum lactate, Acute Physiology and Chronic Health Evaluation II, and maximum dose of norepinephrine day 1) (hazard ratio, 2.97; 95% CI, 2.20-4.00; p < 0.001 and hazard ratio, 1.89; 95% CI, 1.26-2.85; p = 0.002 in Vasopressin and Septic Shock trial and St. Paul's Hospital, respectively). There was no difference in the area under the plasma vasopressin concentration curve between patients with and without serious adverse events (p = 0.1). The AA genotype of rs28418396 single-nucleotide polymorphism (near the arginine vasopressin receptor 1b gene) was significantly associated with serious adverse events in discovery and validation cohorts (p = 0.001 and p = 0.04, respectively). Serious adverse events associated with vasopressin and norepinephrine in patients who have septic shock are associated with increased mortality and morbidity. AA genotype of rs28418396 single-nucleotide polymorphism near the arginine vasopressin receptor 1b gene is associated with serious adverse events. The mechanism of this association requires investigation.


Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson's disease
To determine the effect of melatonin (MEL) administration on ciclooxigenase 2 (COX-2) activity and serum concentration of nitric oxide metabolites, lipoperoxides and glutathione peroxidase (GPx) activity in patients with Parkinson's disease. Prospective double-blind randomized clinical pilot trial. 13 patients were included and two groups were formed: MEL at doses of 25 mg orally every 12 hours for 12 months and placebo with corn starch. Patients were assessed using the Unified Parkinson's Disease Scale. A blood sample was taken at baseline and every 3 months until 12 months. COX-2 activity decreased as did nitrates/nitrites (3, 6 and 9 months) and lipoperoxides (9 and 12 months); GPx exhibited no significant differences.


The effect of sugar, amino acid, metal ion, and NaCl on model Maillard reaction under pH control.
The color intensities was determined of Maillard reaction products (MRPs) prepared by heating each of five sugars (maltose, fructose, glucose, arabinose, and xylose) with each of 12 amino acids (aspartic acid, glutamic acid, alanine, leucine, isoleucine, valine, proline, serine, cysteine, phenylalanine, arginine, and lysine). The remaining percentages of glucose and rate of change of color intensity due to the addition of a metal ion and NaCl were monitored for nine MRPs that had been formed between glucose and each of nine amino acids (aspartic acid, glutamic acid, alanine, valine, serine, cysteine, phenylalanine, arginine, and lysine). Model MRPs were prepared in a block heater at 100 degrees C for 1-12 h with the pH value controlled at 6.5. The resulting color intensity of each MRPs formed from the basic amino acids was greater due to the higher reactivity than those from the acidic amino acids. The remaining percentage of glucose in each MRPs from the basic amino acids was lower than those from the acidic amino acids. The MRPs from the nonpolar amino acids showed an intermediate color intensity and remaining percentages of glucose between those formed from the basic and acidic amino acids. Browning tended to be accelerated in the presence of metal ions, especially Fe2+ and Cu2+, although it was affected by the property of the amino acid and heating time as well as by the type of metal ion. On the other hand, browning was greatly inhibited by a high concentration of NaCl.


Can the common-sense model predict adherence in chronically ill patients? A meta-analysis.
The aim of this meta-analysis was to explore whether mental representations, derived from the common-sense model of illness representations (CSM), were able to predict adherence in chronically ill patients. Electronic databases were searched for studies that used the CSM and measured adherence behaviour in chronically ill patients. Correlations from the included articles were meta-analysed using a random-size effect model. A moderation analysis was conducted for the type of adherence behaviour. The effect sizes for the different mental representations and adherence constructs ranged from -0.02 to 0.12. Further analyses showed that the relationship between the mental representations and adherence did not differ by the type of adherence behaviour. The low-effect sizes indicate that the relationships between the different mental representations of the CSM and adherence are very weak. Therefore, the CSM may not be the most appropriate model to use in predictive studies of adherence.


VEGF reverts the cognitive impairment induced by a focal traumatic brain injury during the development of rats raised under environmental enrichment.
The role of VEGF in the nervous system is extensive; apart from its angiogenic effect, VEGF has been described as a neuroprotective, neurotrophic and neurogenic molecule. Similar effects have been described for enriched environment (EE). Moreover, both VEGF and EE have been related to improved spatial memory. Our aim was to investigate the neurovascular and cognitive effects of intracerebrally-administered VEGF and enriched environment during the critical period of the rat visual cortex development. Results showed that VEGF infusion as well as enriched environment induced neurovascular and cognitive effects in developing rats. VEGF administration produced an enhancement during the learning process of enriched animals and acted as an angiogenic factor both in primary visual cortex (V1) and dentate gyrus (DG) in order to counteract minipump implantation-induced damage. This fact revealed that DG vascularization is critical for normal learning. In contrast to this enriched environment acted on the neuronal density of the DG and V1 cortex, and results showed learning enhancement only in non-operated rats. In conclusion, VEGF administration only has effects if damage is observed due to injury. Once control values were reached, no further effects appeared, showing a ceiling effect. Our results strongly support that in addition to neurogenesis, vascularization plays a pivotal role for learning and memory.


Dissociation between rewarding and psychomotor effects of opiates: differential roles for glutamate receptors within anterior and posterior portions of the ventral tegmental area.
The rewarding effects of drugs of abuse are thought to be dependent on the mesocorticolimbic dopamine system, which originates in the ventral tegmental area (VTA) and projects into the nucleus accumbens (NAC) and other forebrain regions. Heroin, by inhibiting GABAergic interneurons in the VTA, induces local dopaminergic activation and release in the NAC terminals. The role of other basic neurotransmitter systems, such as glutamate in the VTA, in mediating the rewarding effect of addictive drugs, is less established. We explored whether blockade of glutamate receptors in subregions of the VTA modulate the rewarding properties and/or the development of psychomotor changes induced by opiates. Administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an AMPA/kainate receptor antagonist) into the anterior VTA blocked the rewarding effects of opiates in both the conditioned place preference and the self-administration paradigms without affecting the gradual increase of the psychomotor response to opiates. In contrast, administration of CNQX into the posterior VTA did not affect the rewarding properties of opiates, but blocked the initial sedative effect of opiates and the gradual increase of the psychomotor response to the drug. These findings suggest a critical role for glutamate receptors in the VTA in opiate reward, as well as behavioral and anatomical dissociation between the rewarding and psychomotor effects of opiates.


High dose magnesium sulfate exposure induces apoptotic cell death in the developing neonatal mouse brain.
Magnesium sulfate (MgSO4) is often used as a treatment for pre-eclampsia/eclampsia and preterm labor, resulting in the exposure of a significant number of neonates to this drug despite a lack of evidence suggesting that it is safe, or effective as a tocolytic. While there is evidence that MgSO4 may be neuroprotective in perinatal brain injury, recent reviews have suggested that the effects are dependent upon dose, and that higher doses may actually increase neonatal morbidity and mortality. There is a lack of evidence investigating the neurotoxic effects of neonatal magnesium (Mg) exposure on the developing brain, specifically in terms of neurodevelopmental apoptosis, a cell-killing phenomenon known to be potentiated by other drugs with mechanisms of action at Mg-binding sites (i.e. NMDA receptor antagonists such as MK-801, ketamine, and PCP). To investigate the effects of Mg exposure on the neonatal mouse brain at different postnatal ages to determine whether MgSO4 treatment causes significant cell death in the developing mouse brain. C57Bl/6 mice were treated with four doses of MgSO4 (250 mg/kg) on postnatal days 3 (P3), 7 (P7) or 14 (P14). Caspase-3 immunohistochemistry, cupric silver staining, and electron microscopy techniques were used to examine Mg-treated brains for neurotoxic effects. Qualitative evaluation using cupric silver staining revealed widespread damage throughout the brain in P7 animals. Results of electron microscopy confirmed that the cell death process was apoptotic in nature. Quantitative evaluation of damage to the cortex, caudate-putamen, hippocampus, thalamus, and cerebellum showed that Mg treatment caused significant brain damage in animals treated on P3 and P7, but not P14. Administration of high doses of Mg may be detrimental to the fetal brain, particularly if exposure occurs during critical periods of neurodevelopment.


Telmisartan and Rosuvastatin Synergistically Ameliorate Dementia and Cognitive Impairment in Older Hypertensive Patients With Apolipoprotein E Genotype.
Objective: To investigate the effect of telmisartan, rosuvastatin, or their combination on dementia and to understand the impact of apolipoprotein E (APOE) genotype on the effect of the medications in older patients with hypertension. Methods: This is a double-blind, randomized, and placebo-controlled trial using a 2 × 2 factorial design. Between April 2008 and November 2010, 1,244 hypertensive patients aged ≥60 years without cognitive impairment were recruited from communities in six cities in Shandong area, China. Patients were randomized into telmisartan and rosuvastatin administration after a 2-week washout period. APOE genotype was identified at the baseline. Possible dementia was determined using the combination of the global cognitive function and Assessment of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Results: Over an average follow-up of 7 [interquartile range (IQR): 6.7-7.2] years, telmisartan and rosuvastatin significantly reduced the cognitive impairment progression and the incidence of dementia. There was a synergistic interaction between telmisartan and rosuvastatin to reduce the cognitive impairment and the incidence of dementia (P adjusted < 0.001). The cognitive impairment progression and the risk of dementia were higher in the hypertensive patients with APOE ε4 allele than in those without APOE ε4 allele. Rosuvastatin medication significantly alleviated the cognitive impairment progression and the risks of dementia in patients with APOE ε4 allele. Conclusion: The combination of telmisartan and rosuvastatin might be an effective prevention and/or treatment strategy for cognitive impairment and dementia, especially in hypertensive patients with the APOE ε4 allele. Clinical Trial Registration: www.ClinicalTrials.gov, ChiCTR.org.cn, identifier ChiCTR-IOR-17013557. Registered on April 12, 2017 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=23121.


[Delirium tremens in Israel].
We discuss pathogenetic aspects (biochemical, pharmacological) of delirium tremens (DT) in accordance with the acute clinical processes, the development of psychosis, and preventive treatment used in the various stages. A typical patient, a 33-year-old man, and the difficulties in diagnosis and treatment are presented and conclusions from the dangerous behavior of the patient are drawn.


Identification of 3,4-Dihydroisoquinoline-2(1H)-sulfonamides as potent carbonic anhydrase inhibitors: synthesis, biological evaluation, and enzyme--ligand X-ray studies.
Following previous studies we herein report the exploration of the carbonic anhydrase (CA, EC 126.96.36.199) inhibitory effects and enzyme selectivity of a small class of 1-(cyclo)alkylisoquinolines containing a sulfonamide function considered a key feature for inhibiting CA. The results of enzymatic assays against human (h) CA isoforms, hCA I and hCA II (cytosolic, ubiquitous enzymes), hCA IX (transmembrane, tumor-associated), and hCA XIV (transmembrane), suggested that the presence of C-1 small substituents on isoquinoline scaffold controls both inhibitory potency and selectivity. Some derivatives showed potent hCA IX and hCA XIV inhibitory effects at nanomolar concentrations as well as low affinity for the ubiquitous hCA II. Moreover, we report the X-ray crystal structure of one of these derivatives in complex with dominant human isoform II, thus confirming the sulfonamide--zinc interactions. Finally, the results of docking experiments suggested the hypothetic interactions in the catalytic binding site for the most active and selective hCA IX and hCA XIV inhibitor.


Occurrence of Whitlockite in Chondritic Meteorites.
The first reported occurrence of the tricalcium phosphate mineral, whitlockite, in several chondrites is described. The identification of this mineral and previously reported chlorapatite were made by x-ray diffraction; the results do not confirm the postulated existence of meteoritic merrillite. Some other remarks pertaining to the existence of merrillite are presented.


Tobacco-alcohol optic neuropathy--clinical challenges in diagnosis.
Part of the large group of nutritional and toxic optic neuropathies, tobacco-alcohol optic neuropathy is a disease often underdiagnosed or detected at a stage when the full recovery of vision is not possible. This article summarizes its signs and symptoms, describes the pathophysiological processes involved and provides the necessary information for diagnosis and treatment of the entity previously known as tobacco-alcohol amblyopia, reporting in the end, a challenging case along with its findings.


Matter Dependence of the Four-Loop Cusp Anomalous Dimension.
We compute analytically the matter-dependent contributions to the quartic Casimir term of the four-loop lightlike cusp anomalous dimension in QCD, with n_{f} fermion and n_{s} scalar flavors. The result is extracted from the double pole of a scalar form factor. We adopt a new strategy for the choice of master integrals with simple analytic and infrared properties, which significantly simplifies our calculation. To this end, we first identify a set of integrals for which the integrands have a d log form, and are hence expected to have uniform transcendental weight. We then perform a systematic analysis of the soft and collinear regions of loop integration and build linear combinations of integrals with a simpler infrared pole structure. In this way, only integrals with ten or fewer propagators are needed for obtaining the cusp anomalous dimension. These integrals are then computed via the method of differential equations through the addition of an auxiliary scale. Combining our result with that of a parallel paper, we obtain the complete n_{f} dependence of the four-loop cusp anomalous dimension in QCD. Finally, using known numerical results for the gluonic contributions, we obtain an improved numerical prediction for the cusp anomalous dimension in N=4 super Yang-Mills theory.


Implementation and reimbursement of remote monitoring for cardiac implantable electronic devices in Europe: a survey from the health economics committee of the European Heart Rhythm Association.
Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) permits early detection of arrhythmias, device, and lead failure and may also be useful in risk-predicting patient-related outcomes. Financial benefits for patients and healthcare organizations have also been shown. We sought to assess the implementation and funding of RM of CIEDs, including conventional pacemakers (PMs), implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices in Europe. Electronic survey from 43 centres in 15 European countries. In the study sample, RM was available in 22% of PM patients, 74% of ICD patients, and 69% of CRT patients. The most significant perceived benefits were the early detection of atrial arrhythmias in pacemaker patients, lead failure in ICD patients, and worsening heart failure in CRT patients. Remote monitoring was reported to lead a reduction of in-office follow-ups for all devices. The most important reported barrier to the implementation of RM for all CIEDs was lack of reimbursement (80% of centres). Physicians regard RM of CIEDs as a clinically useful technology that affords significant benefits for patients and healthcare organizations. Remote monitoring, however, is perceived as increasing workload. Reimbursement for RM is generally perceived as a major barrier to implementation.


Challenging Assumptions: What Do We Need to Address in Our Disaster Risk Reduction Efforts?
Introduction Specific knowledge and skills are required, especially in the first 72 hours post-disaster, to bridge the time gap until essential services are restored and Emergency Medical Services (EMS) can focus on individuals' needs. This study explores disaster knowledge and preparedness in the first 72 hours as a function of the individual's engagement in discussions about disasters, and several other factors (both at personal and community/country level), as well as the entities/organizations perceived by the individual as being responsible for disaster risk reduction (DRR) education. A prospective, cross-sectional survey of 3,829 final-year high-school students was conducted in nine countries with different levels of disaster risk and economic development. Regression analyses examined the relationship between a 72-hour disaster preparedness composite outcome (ability to make water safe for drinking, knowledge of water potability, home evacuation skill, and improvising a safe room) and a series of independent predictors. Respondents from countries with lower economic development were significantly better prepared for the first 72 hours post-disaster than those from developed countries (OR=767.45; CI=13.75-48,822.94; P=.001). While several independent predictors showed a significant main effect, combined disaster risk education (DRE) efforts, as a partnership between school and local government, had the best predictive value (OR=3.52; CI=1.48-8.41; P=.005). Disaster preparedness in final-year high-school students is significantly better in developing countries. Further improvement requires a convergent effort in aligning the most effective educational policies and actions to best address the individual's and the community needs. Codreanu TA , Ngo H , Robertson A , Celenza A . Challenging assumptions: what do we need to address in our disaster risk reduction efforts? Prehosp Disaster Med. 2017;32(2):134-147.


Emotional memory for central and peripheral details in children with callous-unemotional traits.
A limited number of studies have shown that adults and adolescents with psychopathic traits suffer from emotional memory impairment. The present study examined whether this finding could be replicated in a sample of children between 8 and 12 years of age with callous-unemotional (CU) traits. Children with high CU traits (n=24) were compared with children with low CU traits (n=18) with regard to performance on a peripheral memory recognition test that examined memory for central and peripheral components of neutral and negative pictures. Results showed that overall recognition rates did not differ between the high- and low-CU groups. For negative pictures, both groups demonstrated better recognition of the central component at the expense of the peripheral component, while for neutral pictures, the peripheral component was better recognized than the central component. This study is the first to demonstrate that children with high CU traits do not suffer from an impaired emotional memory.


Atomistic simulation of lipid and DiI dynamics in membrane bilayers under tension.
Membrane tension modulates cellular processes by initiating changes in the dynamics of its molecular constituents. To quantify the precise relationship between tension, structural properties of the membrane, and the dynamics of lipids and a lipophilic reporter dye, we performed atomistic molecular dynamics (MD) simulations of DiI-labeled dipalmitoylphosphatidylcholine (DPPC) lipid bilayers under physiological lateral tensions ranging from -2.6 mN m(-1) to 15.9 mN m(-1). Simulations showed that the bilayer thickness decreased linearly with tension consistent with volume-incompressibility, and this thinning was facilitated by a significant increase in acyl chain interdigitation at the bilayer midplane and spreading of the acyl chains. Tension caused a significant drop in the bilayer's peak electrostatic potential, which correlated with the strong reordering of water and lipid dipoles. For the low tension regime, the DPPC lateral diffusion coefficient increased with increasing tension in accordance with free-area theory. For larger tensions, free area theory broke down due to tension-induced changes in molecular shape and friction. Simulated DiI rotational and lateral diffusion coefficients were lower than those of DPPC but increased with tension in a manner similar to DPPC. Direct correlation of membrane order and viscosity near the DiI chromophore, which was just under the DPPC headgroup, indicated that measured DiI fluorescence lifetime, which is reported to decrease with decreasing lipid order, is likely to be a good reporter of tension-induced decreases in lipid headgroup viscosity. Together, these results offer new molecular-level insights into membrane tension-related mechanotransduction and into the utility of DiI in characterizing tension-induced changes in lipid packing.


Global gene expression in Escherichia coli biofilms.
It is now apparent that microorganisms undergo significant changes during the transition from planktonic to biofilm growth. These changes result in phenotypic adaptations that allow the formation of highly organized and structured sessile communities, which possess enhanced resistance to antimicrobial treatments and host immune defence responses. Escherichia coli has been used as a model organism to study the mechanisms of growth within adhered communities. In this study, we use DNA microarray technology to examine the global gene expression profile of E. coli during sessile growth compared with planktonic growth. Genes encoding proteins involved in adhesion (type 1 fimbriae) and, in particular, autoaggregation (Antigen 43) were highly expressed in the adhered population in a manner that is consistent with current models of sessile community development. Several novel gene clusters were induced upon the transition to biofilm growth, and these included genes expressed under oxygen-limiting conditions, genes encoding (putative) transport proteins, putative oxidoreductases and genes associated with enhanced heavy metal resistance. Of particular interest was the observation that many of the genes altered in expression have no current defined function. These genes, as well as those induced by stresses relevant to biofilm growth such as oxygen and nutrient limitation, may be important factors that trigger enhanced resistance mechanisms of sessile communities to antibiotics and hydrodynamic shear forces.


Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes: A randomized controlled trial.
Proteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants. To compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants. FF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively. Compared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups. Contrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.


Needs for nurses to provide spiritual care and their associated influencing factors among elderly inpatients with stroke in China: A cross-sectional quantitative study.
To investigate the spiritual care needs and associated influencing factors among elderly inpatients with stroke, and to examine the correlations among spiritual care needs, spiritual well-being, self-perceived burden, self-transcendence, and social support. A cross-sectional quantitative design was implemented, and the STROBE Checklist was used as the foundation of the study. A convenience sample of 458 elderly inpatients with stroke was selected from three hospitals in China. The sociodemographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Self-Perceived Burden Scale, the Chinese Self-Transcendence Scale, and the Perceived Social Support Scale were used. Descriptive statistics, correlation, Student's t-test, ANOVA, non-parametric, and multiple linear regression analyses were used to analyze the data. The total score of spiritual care needs was 29.82 ± 7.65. Spiritual care needs were positively correlated with spiritual well-being (r = 0.709, p < 0.01), self-transcendence (r = 0.710, p < 0.01), and social support (r = 0.691, p < 0.01), whereas being negatively correlated with self-perceived burden (r = -0.587, p < 0.01). Religious beliefs, educational level, residence place, disease course, spiritual well-being, self-perceived burden, self-transcendence, and social support were found to be the main influencing factors. The spiritual care needs were prevalent and moderate. It is suggested that nurses should enhance spiritual care knowledge and competence, take targeted spiritual care measures according to inpatients' individual personality traits or characteristics and differences of patients, reduce their self-perceived burden and improve their spiritual well-being, self-transcendence and social support in multiple ways and levels, so as to meet their spiritual care needs to the greatest extent and enhance their spiritual comfort.


[The characteristics of the reproduction of time intervals and the individual structure of the EEG in man].
The perception of time by humans was studied by the method of time reproduction. The EEG was recorded in Os, Od, Cs, Cd, Fs and Fd derivations. The relative EEG spectral power was determined in the delta-1, delta-2, theta, alpha, beta-1, and beta-2 ranges. All the subjects were divided in two groups: I--those who reproduced time-intervals with a delay, and II--those who were ahead in their reproduction. The spectral power of the delta-rhythm was significantly lower and that of the beta-rhythm higher in the subjects of the I than of the II group. In subjects of the II group total power of the beta range (beta-1 + beta-2) was significantly less than that in the delta-range (delta-1 + delta-2). This ratio was inverse in subjects of the I group. The described relationships were expressed both in the background EEG and during functional loads in all the studied derivations.


Multicenter Clinical Evaluation of the Luminex Aries Flu A/B & RSV Assay for Pediatric and Adult Respiratory Tract Specimens.
Influenza A and B viruses and respiratory syncytial virus (RSV) are three common viruses implicated in seasonal respiratory tract infections and are a major cause of morbidity and mortality in adults and children worldwide. In recent years, an increasing number of commercial molecular tests have become available to diagnose respiratory viral infections. The Luminex Aries Flu A/B & RSV assay is a fully automated sample-to-answer molecular diagnostic assay for the detection of influenza A, influenza B, and RSV. The clinical performance of the Aries Flu A/B & RSV assay was prospectively evaluated in comparison to that of the Luminex xTAG respiratory viral panel (RVP) at four North American clinical institutions over a 2-year period. Of the 2,479 eligible nasopharyngeal swab specimens included in the prospective study, 2,371 gave concordant results between the assays. One hundred eight specimens generated results that were discordant with those from the xTAG RVP and were further analyzed by bidirectional sequencing. Final clinical sensitivity values of the Aries Flu A/B & RSV assay were 98.1% for influenza A virus, 98.0% for influenza B virus, and 97.7% for RSV. Final clinical specificities for all three pathogens ranged from 98.6% to 99.8%. Due to the low prevalence of influenza B, an additional 40 banked influenza B-positive specimens were tested at the participating clinical laboratories and were all accurately detected by the Aries Flu A/B & RSV assay. This study demonstrates that the Aries Flu A/B & RSV assay is a suitable method for rapid and accurate identification of these causative pathogens in respiratory infections.


Comparison of rest-break interventions during a mentally demanding task.
Research is scarce on ways to enhance the effect of rest breaks during mentally demanding tasks. The present study investigated the effectiveness of two rest-break interventions on well-being during an academic lecture. Sixty-six students (53 females, mean age 22.5 years) enrolled in two different university classes of 4-hr duration participated in the study. Two measures of well-being (fatigue and vigor) were assessed immediately before, after, and 20 minutes after the break. A control condition without a break as well as an unstructured break was compared with breaks either encompassing physical activity or a relaxation exercise. Compared with the nonbreak condition, the unstructured rest break led to an increase in vigor, the exercise break as well as the relaxation break both to an increase in vigor and a decrease in fatigue at 20-min post break. Compared with the unstructured break, exercise led to an (additional) increase in vigor and relaxation to an (additional) decrease in fatigue at 20-min post break. Thus, the effects of rest breaks during mentally demanding tasks can be enhanced by engaging in physical activity or relaxation exercises, with effects lasting at least as long as 20 min into the continuation of the task.


Validation of measures of food insecurity and hunger.
The most recent survey effort to determine the extent of food insecurity and hunger in the United States, the Food Security Supplement, included a series of questions to assess this complex phenomenon. The primary measure developed from this Food Security Supplement was based on measurement concepts, methods and items from two previously developed measures. This paper presents the evidence available that questionnaire-based measures, in particular the national food security measure, provide valid measurement of food insecurity and hunger for population and individual uses. The paper discusses basic ideas about measurement and criteria for establishing validity of measures and then uses these criteria to structure an examination of the research results available to establish the validity of food security measures. The results show that the construction of the national food security measure is well grounded in our understanding of food insecurity and hunger, its performance is consistent with that understanding, it is precise within usual performance standards, dependable, accurate at both group and individual levels within reasonable performance standards, and its accuracy is attributable to the well-grounded understanding. These results provide strong evidence that the Food Security Supplement provides valid measurement of food insecurity and hunger for population and individual uses. Further validation research is required for subgroups of the population, not yet studied for validation purposes, to establish validity for monitoring population changes in prevalence and to develop and validate robust and contextually sensitive measures in a variety of countries that reflect how people experience and think about food insecurity and hunger.


Use of Chitosan from Southern King Crab to Develop Films Functionalized with RGD Peptides for Potential Tissue Engineering Applications.
Southern King Crab (SKC) represents an important fishery resource that has the potential to be a natural source of chitosan (CS) production. In tissue engineering, CS is very useful to generate biomaterials. However, CS has a lack of signaling molecules that facilitate cell-substrate interaction. Therefore, RGD (arginine-glycine-aspartic acid) peptides corresponding to the main integrin recognition site in extracellular matrix proteins have been used to improve the CS surface. The aim of this study was to evaluate in vitro cell adhesion and proliferation of CS films synthesized from SKC shell wastes functionalized with RGD peptides. The FTIR spectrum of CS isolated from SKC shells (SKC-CS) was comparable to commercial CS. Thermal properties of films showed similar endothermic peaks at 53.4 and 53.0 °C in commercial CS and SKC-CS, respectively. The purification and molecular masses of the synthesized RGD peptides were confirmed using HPLC and ESI-MS mass spectrometry, respectively. Mouse embryonic fibroblast cells showed higher adhesion on SKC-CS (1% w/v) film when it was functionalized with linear RGD peptides. In contrast, a cyclic RGD peptide showed similar adhesion to control peptide (RDG), but the highest cell proliferation was after 48 h of culture. This study shows that functionalization of SKC-CS films with linear or cyclic RGD peptides are useful to improve effects on cell adhesion or cell proliferation. Furthermore, our work contributes to knowledge of a new source of CS to synthesize constructs for tissue engineering applications.


How do young and senior cytopathologists interact with digital cytology?
Today thanks to the technological advances in information technology the scenario of utilization of digital cytology has radically changed. New competitive systems, such as client-server architectures are now available in digital cytology. Their application in telemedicine should be investigated. A new interactive tool designed for the final destination user (the cytopathologist) has been proposed. Taking into account the different expertise of the subjects of the study, the investigation was focused both on the senior cytopathologist and on the younger student pathologist. The methodology was tested on 10 students of a Master in cytopathology and on 3 senior cytopathologists. The study showed that the use of digital cytology applications is effective and feasible for telediagnosis. In particular, the study on younger and senior expert investigators showed that, although they interacted with the novel technology of the virtual slide in a different manner, all of them reached the objective of a "correct diagnosis". This investigation, in consideration of the effectiveness of the digital cytology, also showed other indirect and tangible cost-beneft and quantitative advantages. In particular for the learning methodologies for the students of the Master itself and for the biomedical personnel involved in diagnosis.