Analysis of human serum and whole blood for mineral content by ICP-MS and ICP-OES: development of a mineralomics method.
Minerals are inorganic compounds that are essential to the support of a variety of biological functions. Understanding the range and variability of the content of these minerals in biological samples can provide insight into the relationships between mineral content and the health of individuals. In particular, abnormal mineral content may serve as an indicator of illness. The development of robust, reliable analytical methods for the determination of the mineral content of biological samples is essential to developing biological models for understanding the relationship between minerals and illnesses. This paper describes a method for the analysis of the mineral content of small volumes of serum and whole blood samples from healthy individuals. Interday and intraday precision for the mineral content of the blood (250 μL) and serum (250 μL) samples was measured for eight essential minerals--sodium (Na), calcium (Ca), magnesium (Mg), potassium (K), iron (Fe), zinc (Zn), copper (Cu), and selenium (Se)--by plasma spectrometric methods and ranged from 0.635 to 10.1% relative standard deviation (RSD) for serum and 0.348-5.98% for whole blood. A comparison of the determined ranges for ten serum samples and six whole blood samples provided good agreement with literature reference ranges. The results demonstrate that the digestion and analysis methods can be used to reliably measure the content of these minerals and potentially of other minerals.


How a purine salvage enzyme singles out the right base.
Two phosphoribosyltransferases in the purine salvage pathway exhibit exquisite substrate specificity despite the chemical similarity of their distinct substrates, but the basis for this discrimination was not fully understood. Ozeir et al. now employ a complementary biochemical, structural, and computational approach to deduce the chemical constraints governing binding and propose a distinct mechanism for catalysis in one of these enzymes, adenine phosphoribosyltransferase. These insights, built on data from an unexpected finding, finally provide direct answers to key questions regarding these enzymes and substrate recognition more generally.


Production of Feminized Seeds of High CBD Cannabis sativa L. by Manipulation of Sex Expression and Its Application to Breeding.
The use of the cannabis plant as a source of therapeutic compounds is gaining great importance since restrictions on its growth and use are gradually reduced throughout the world. Intensification of medical (drug type) cannabis production stimulated breeding activities aimed at developing new, improved cultivars with precisely defined, and stable cannabinoid profiles. The effects of several exogenous substances, known to be involved in sex expressions, such as silver thiosulfate (STS), gibberellic acid (GA), and colloidal silver, were analyzed in this study. Various concentrations were tested within 23 different treatments on two high cannabidiol (CBD) breeding populations. Our results showed that spraying whole plants with STS once is more efficient than the application of STS on shoot tips while spraying plants with 0.01% GA and intensive cutting is ineffective in stimulating the production of male flowers. Additionally, spraying whole plants with colloidal silver was also shown to be effective in the induction of male flowers on female plants, since it produced up to 379 male flowers per plant. The viability and fertility of the induced male flowers were confirmed by fluorescein diacetate (FDA) staining of pollen grains, in vitro and in vivo germination tests of pollen, counting the number of seeds developed after hybridization, and evaluating germination rates of developed seeds. Finally, one established protocol was implemented for crossing selected female plants. The cannabinoid profile of the progeny was compared with the profile of the parental population and an improvement in the biochemical profile of the breeding population was confirmed. The progeny had a higher and more uniform total CBD (tCBD) to total tetrahydrocannabinol (tTHC) ratio (up to 29.6; average 21.33 ± 0.39) compared with the original population (up to 18.8; average 7.83 ± 1.03). This is the first comprehensive report on the induction of fertile male flowers on female plants from dioecious medical cannabis (Cannabis sativa L.).


A high-finesse broadband optical cavity using calcium fluoride prism retroreflectors.
A high-finesse broadband optical cavity has been developed for use in the ultraviolet and visible region using Brewster-angle calcium fluoride (CaF₂) prism retroreflectors. Prior to prism construction, optical loss measurements of CaF₂ windows were performed using cavity ring-down spectroscopy at 250 nm. Total optical loss showed high spatial correlation with crystal birefringence, which was partially mitigated by orienting the <111> crystal axis with the laser beam. Prism reflectivity was measured using cavity ring-down spectroscopy and found to be 99.77% at 250 nm and 99.96% at 500 nm, allowing for relatively high-finesse operation over hundreds of nm bandwidth with a single cavity.


Clinical impact of prandial state, exercise, and site preparation on the equivalence of alternative-site blood glucose testing.
To determine whether clinically significant differences exist in fasting blood glucose (BG) at the forearm, palm, and thigh relative to the fingertip; to assess the impact of prandial status by comparing BG between alternative sites and the fingertip at several time intervals after carbohydrate intake; to assess the effects of moderate brief exercise on site-to-site differences in BG; to evaluate the impact of site preparation by local rubbing on alternative-site testing (AST) equivalence; and to determine levels of perceived pain and satisfaction associated with AST. Fasting BG was measured using the One Touch Ultra (LifeScan, Milpitas, CA) at the fingertip, palm, thigh, and each forearm (with local rubbing) in 86 patients with type 2 diabetes. A 40-g carbohydrate meal was consumed and BG was again measured from each site at 60, 90, and 120 min postmeal, with an additional forearm test at 90 min without local rubbing. Patients then exercised for 15 min with repeat BG at each site. Differences in BG between sites were assessed using repeated-measures ANOVA and regression analyses. Significant differences in BG at alternative sites were found 60 min postmeal (P = 0.0003) and postexercise (P = 0.037). Specifically, clinically significant differences (expressed as percent difference from the fingertip) at 60 min include -8.8 +/- 10.8% at the forearm and -13.7 +/- 10.7% at the thigh, and postexercise +19.1 +/- 19.1% at the forearm and +15.6 +/- 22.6% at the thigh. However, no significant differences were observed between sites in either the fasting state or at 90 and 120 min postmeal. The dynamic results suggest a time lag in equilibration of forearm and thigh BG during periods of rapid glucose change. Palm and fingertip BG test results were similar at all time points. AST results are consistent with fingertip BG results in both the fasting state and 2 h postmeal; no benefit from site preparation by local rubbing was noted. However, testing at sites other than the hand cannot be recommended 1 h postmeal or immediately after exercise. AST is equivalent and appropriate for use at testing times commonly used in clinical practice.


Frontal midline theta rhythm and eyeblinking activity during a VDT task and a video game: useful tools for psychophysiology in ergonomics.
The necessity of psychophysiological research in ergonomics has gradually been recognized in Japan. In this paper, frontal midline theta rhythm (Fm-theta) and eyeblinking are recommended as tools in this field, especially for assessing workers' attention concentration, mental workload, fatigue, and interest during VDT work at the workplace and playing video games at home. In experiment 1, Fm-theta and eyeblink rates were measured in 10 Japanese abacus experts (Group E) and 10 normal students (Group C) during a visual search task with VDT. Memory load affected all measures. The amount of Fm-theta appeared more in Group E than Group C, but blink rate was lower in Group E than in Group C. As abacus experts have such highly developed skills in concentration, the result indicates that the amount of Fm-theta would be a good index of attention concentration in VDT workers. The second experiment was done with 10 school-aged children as subjects during three visual tasks: video game, mental test and animation. Amounts of Fm-theta and the degree of blink inhibition were maximum while playing the video game, which all subjects reported they most preferred, and minimum while watching animation, which eight subjects reported to be most boring. An interesting task would seem to provoke Fm-theta and inhibit eyeblink activity. From these two experiments, Fm-theta and eyeblink rate would appear to be good indices of attention concentration and task pleasantness of a mental task using VDT.


Tracing the ontogeny of stomatal clusters in Arabidopsis with molecular markers.
The origin and process by which the mosaic of the different cell types is established during the development of the leaf epidermis in Arabidopsis are largely unknown, although the recent characterization of two mutants which develop stomatal clusters (four lips (flp) and too many mouths (tmm)) has opened up the possibility for genetic dissection of the stomata spacing. By using growth conditions which limit gas exchange with the open atmosphere, stomatal clusters that look like phenocopies of flp and tmm have been induced, suggesting that stomata spacing is under environmental as well as genetic control in Arabidopsis. The origin of these clusters has been addressed by following promoter activity for genes that are markers for competence for cell division (cdc2aAt), mitotic activity (cyc1aAt), and guard mother cell and developing guard cell identity (rha1). Their different expression patterns in the various cell types during epidermal differentiation and the asynchrony in the development of the various stomata that constitute each cluster suggest that these stomatal clusters derive from a single protodermal cell through a process that involves changes in cell fate in a subset of subsidiary cells. It was also found that guard cells express cdc2aAt and cyc1aAt, supporting the idea that they may remain competent for cell division.


Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product.
The amino-terminal amino acid sequences of gp85 and gp37, the envelope glycoproteins of Rous sarcoma virus (RSV), were determined. Alignment of these sequences with the amino acid sequence predicted from the complete nucleotide sequence of the Prague strain of RSV, subgroup C (PR-C), has allowed us to delineate the env gene-coding region of this virus. The coding sequences for gp85 and gp37 have been placed in an open reading frame that extends from nucleotide 5045 to nucleotide 6862 and predict sizes of 341 amino acids (36,962 molecular weight) for gp85 and 198 amino acids (21,566 molecular weight) for gp37. Carbohydrate makes a significant contribution to the observed molecular weights of these polypeptides--the amino acid sequence contains 14 potential glycosylation sites (Asn-X-Ser/Thr) in gp85 and two in gp37. Experiments aimed at estimating the number of carbohydrate side chains yielded results consistent with most or all of these sites being occupied. Although an initiation codon is located early (codon 4) in the open reading frame, it is likely that splicing yields an mRNA on which translation initiates at the same AUG as that of the gag gene to produce a nascent polypeptide in which gp85 is preceded by a 62-amino-acid-long leader peptide. This leader contains the hydrophobic sequence (signal sequence) necessary for translocation across the endoplasmic reticulum and is completely removed from the env gene product during translation. The polyprotein precursor, Pr95env, is cleaved to gp85 and gp37 at the carboxyl side of the basic sequence:-Arg-Arg-Lys-Arg-. gp85 is attached through a disulphide linkage to gp37, and although the positions of the cysteines involved in this linkage are not known, the presence of a 27-amino-acid-long hydrophobic region at the carboxy-terminus of gp37 is consistent with its role as a membrane anchor for the viral glycoprotein complex. The location of host range variable regions with respect to the possible tertiary structure of the complex is discussed.


The inhibition of Clostridium chauvoei (jakari strain) neuraminidase activity by methanolic extracts of the stem barks of Tamarindus indicus and Combretum fragrans.
The inhibition of neuraminidase from Clostridium chauvoei (jakari strain) with partially purified methanolic extracts of some plants used in Ethnopharmacological practice was evaluated. Extracts of two medicinal plants, Tamarindus indicus and Combretum fragrans at 100-1000 microg/ml, both significantly reduced the activity of the enzyme in a dose-dependent fashion (P < 0.001). The estimated IC50 values for Tamarindus indicus and Combretum fragrans were 100 and 150 microg/ml respectively. Initial velocity studies conducted, using fetuin as substrate revealed a non-competitive inhibition with the Vmax significantly altered from 500 micromole min(-1) mg(-1) to 240 micromole min(-1) mg(-1) and 340 micromole min(-1) mg(-1) in the presence of Tamarindus indicus and Combretum fragrans respectively. The KM remained unchanged at 0.42 mM. The computed Index of physiological efficiency was reduced from 1.19min(-1) to 0.57min(-1) and 0.75min(-1) with Tamarindus indicus and Combretum fragrans as inhibitors respectively.


Direct and reversible inhibition of estradiol-stimulated prolactin synthesis by antiestrogens in vitro.
The antiestrogens tamoxifen and monohydroxytamoxifen inhibited the estradiol-stimulated increase in prolactin synthesis by dispersed cells in culture derived from immature rat pituitary glands. Monohydroxytamoxifen had a relative binding affinity for the estrogen receptor similar to that of estradiol, whereas tamoxifen's relative binding affinity was approximately 3%. This was consistent with the observation that monohydroxytamoxifen was 30 times more potent than tamoxifen as an antiestrogen in vitro. To avoid the possibility that tamoxifen was fractionally metabolized to monohydroxytamoxifen by the pituitary cells, the p-methyl, p-chloro, and p-fluoro derivatives of tamoxifen that are unlikely to be converted to monohydroxytamoxifen were tested for activity. The substitution did not have a detrimental effect on their ability to inhibit the binding of [3H]estradiol to either rat uterine or pituitary gland estrogen receptors. Similarly, the derivatives of tamoxifen inhibited estradiol-stimulated prolactin synthesis at concentrations that were consistent with their relative binding affinities. Although it is clearly an advantage for tamoxifen to be metabolized to the more potent antiestrogen monohydroxytamoxifen, we have shown that this is not a prerequisite for the antiestrogenic actions of tamoxifen. With the direct actions of antiestrogens established, the pituitary cell system was validated for further structure-activity relationship studies. Overall, the inhibition of estradiol-stimulated prolactin synthesis by antiestrogens is competitive and reversible with estradiol, an effect that can be explained by interactions with the estrogen receptor system.


ELEVATED CARBON DIOXIDE DIFFERENTIALLY ALTERS THE PHOTOPHYSIOLOGY OF THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE) AND EMILIANIA HUXLEYI (HAPTOPHYTA)(1).
Increasing anthropogenic carbon dioxide is causing changes to ocean chemistry, which will continue in a predictable manner. Dissolution of additional atmospheric carbon dioxide leads to increased concentrations of dissolved carbon dioxide and bicarbonate and decreased pH in ocean water. The concomitant effects on phytoplankton ecophysiology, leading potentially to changes in community structure, are now a focus of concern. Therefore, we grew the coccolithophore Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler and the diatom strains Thalassiosira pseudonana (Hust.) Hasle et Heimdal CCMP 1014 and T. pseudonana CCMP 1335 under low light in turbidostat photobioreactors bubbled with air containing 390 ppmv or 750 ppmv CO2 . Increased pCO2 led to increased growth rates in all three strains. In addition, protein levels of RUBISCO increased in the coastal strains of both species, showing a larger capacity for CO2 assimilation at 750 ppmv CO2 . With increased pCO2 , both T. pseudonana strains displayed an increased susceptibility to PSII photoinactivation and, to compensate, an augmented capacity for PSII repair. Consequently, the cost of maintaining PSII function for the diatoms increased at increased pCO2 . In E. huxleyi, PSII photoinactivation and the counter-acting repair, while both intrinsically larger than in T. pseudonana, did not change between the current and high-pCO2 treatments. The content of the photosynthetic electron transport intermediary cytochrome b6/f complex increased significantly in the diatoms under elevated pCO2 , suggesting changes in electron transport function.


Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine.
We report the immunological characterization of three colon carcinoma cell lines, COLO 205, SW620 and SW403, which we selected to combine with cytokine-secreting fibroblasts for the development of an allogeneic tumour cell vaccine. The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens. They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins. The lines presented TAAs in a manner recognized by immune effector cells, which was demonstrated by the lysis of SW620 by HLA-A2-restricted anti-p53 cytotoxic T lymphocytes (CTL). COLO 205 and SW620 were genetically modified to express the co-stimulatory molecule CD80 (B7.1), which increased the ability of the cells to stimulate CTL in vitro. CTL clones derived from HLA-A2+ peripheral blood mononuclear cells stimulated with the CD80-expressing lines lysed the stimulator cell and an HLA-A2+ colon cancer cell line, but did not lyse an isogeneic fibroblast line or an HLA-A2- colon cancer cell line. CTL clones derived from colon carcinoma patients immunized with an allogeneic vaccine containing these lines demonstrated killing of autologous tumour cells, the vaccine cell lines and other HLA-A2+ colon cancer cell lines, but not fibroblasts isogeneic to certain of the target cell lines. Our studies demonstrate that these colon carcinoma cell lines express shared TAAs that can induce CTLs which recognize and lyse other colon carcinoma cells, and support the continued clinical evaluation of the CD80 gene modified allogeneic colon cell/cytokine-secreting fibroblast carcinoma vaccine.


A model integrating donor gene polymorphisms predicts fibrosis after liver transplantation.
Post-transplant liver fibrosis (PTLF) is a common and severe complication in liver recipients. In this study, we assessed the impact of donor liver genetics on the development of PTLF. A total of 232 patients undergoing liver transplantation were included. Twenty-two single nucleotide polymorphisms (SNPs) associated with liver fibrosis were analyzed. Univariate analysis revealed seven donor SNPs to be associated with PTLF. In a multivariate analysis, independent risk factors of PTLF were genetic variation of donor GRP78 rs430397 (OR = 8.99, p = 0.003), GSTP1 rs1695 (OR = 0.13, p = 0.021), miRNA-196a rs12304647 (OR = 16.01, p =0.001), and TNF-α rs1800630 (OR = 79.78, p = 0.001); blood tacrolimus levels at maintenance > 7 ng/ml (OR =7.48, p <0.001); and post-transplant diabetes mellitus (OR = 7.50, p = 0.001). A predictive model that included donor SNPs showed better prognostic ability for PTLF than a model with only clinical parameters (AUROC: 0.863 vs 0.707, P < 0.001). Given that donor gene SNPs are associated with an increased risk of PTLF, this model integrated with donor gene polymorphisms may help clinicians predict PTLF.


Minor laparoscopic liver resection as day-case surgery (without overnight hospitalisation): a pilot study.
Day-case surgery (DCS) has become increasingly popular over recent years, as has laparoscopic liver resection (LLR) for the treatment of benign or malignant liver tumours. The purpose of this prospective study was to demonstrate the feasibility of minor LLR as DCS. Prospective, intention-to-treat, non-randomised study of patients undergoing minor LLR between July 2015 and December 2017. Exclusion criteria were resection by laparotomy, major LLR, difficult locations for minor LLR, history of major abdominal surgery, hepatobiliary procedures without liver parenchyma resection, cirrhosis with Child > A and/or portal hypertension, significant medical history and exclusion criteria for DCS. The primary endpoint was the unplanned overnight admission rate. Secondary endpoints were the reason for exclusion, complication data, criteria for DCS evaluation, satisfaction and compliance with the protocol. One hundred sixty-seven patients underwent liver resection during the study period. LLR was performed in 92 patients (55%), as DCS in 23 patients (25%). Reasons for minor LLR were liver metastasis (n = 9), hepatic adenoma (n = 5), hepatocellular carcinoma (n = 4), ciliated hepatic foregut cyst (n = 2) and other benign tumours (n = 3). All day-case minor LLR, except two patients, consisted of single wedge resection, while one patient underwent left lateral sectionectomy. There were four unplanned overnight admissions (17.4%), one unscheduled consultation (4.3%), two hospital readmissions (8.6%) and no major complications/mortality. Compliance with the protocol was 69.5%. Satisfaction rate was 91%. In selected patients, day-case minor LLR is feasible with acceptable complication and readmission rates. Day-case minor LLR can therefore be legitimately proposed in selected patients.


The Ethics of Dying: Deciphering Pandemic-Resultant Pressures That Influence Elderly Patients' Medical Assistance in Dying (MAiD) Decisions.
The objective of medicine is to provide humans with the best possible health outcomes from the beginning to the end of life. If the continuation of life becomes unbearable, some may evaluate procedures to end their lives prematurely. One such procedure is Medical Assistance in Dying (MAiD), and it is hotly contended in many spheres of society. From legal to personal perspectives, there are strong arguments for its implementation and prohibition. This article intends to add to this rich discourse by exploring MAiD in the context of our current pandemic-ridden society as new pressures from social isolation and guilt threaten the autonomy of vulnerable elderly patients. Although autonomy is of chief importance, variables within our current context undermine otherwise independent decisions. Many older individuals are isolated from their social network, resulting in a decline in their mental health. Individuals in such a state are more likely to request a MAiD outcome. Furthermore, overwhelmed healthcare systems may not adequately address this state, which would normally have prompted a mental health intervention. The future of MAiD is far from settled and careful consideration must be given as new contexts come to light, such as those outlined in this paper.


Modulated Structure Calculated for Superconducting Hydrogen Sulfide.
Compression of hydrogen sulfide using first principles metadynamics and molecular dynamics calculations revealed a modulated structure with high proton mobility which exhibits a diffraction pattern matching well with experiment. The structure consists of a sublattice of rectangular meandering SH- chains and molecular-like H3 S+ stacked alternately in tetragonal and cubic slabs forming a long-period modulation. The novel structure offers a new perspective on the possible origin of the superconductivity at very high temperatures in which the conducting electrons in the SH chains are perturbed by the fluxional motions of the H3 S resulting in strong electron-phonon coupling.


[The place of β-adrenoblockers in the treatment of cardiovascular disease in patients with chronic obstructive pulmonary disease].
Review is devoted to the place of β-adrenoblockers in the treatment of cardiovascular disease (CVD) in patients with chronic obstructive pulmonary disease (COPD). Currently, it is expedient to use cardioselective -adrenoblockers, such as bisoprolol, metoprolol succinate, carvedilol and nebivolol for the treatment of patients with CVD and COPD. Bisoprolol has the greatest (of all the cardioselective β-adrenoblockers) evidence base of data on the efficacy and safety of using in patients with COPD and CVD. While using a cardioselective β-adrenoblockers external respiration function (ERF) should be controlled. When clinical signs of worsening airway conductance appear, and adverse effects on ERF parameters are observed, β-adrenoblockers dosage should be reduced, while maintaining lower respiratory functions need to be canceled. In general, the use of cardioselective β-adrenoblockers in patients with CVD and COPD is safe, and the benefits of the drugs in this group exceed the risks of exacerbation of COPD. If possible the use of 2-agonists should be limited in patients with CVD in the treatment of COPD because of their negative impact on the cardiovascular system - the preferred use of anticholinergic drugs.


Predicting resolution and image quality in RESOLFT and other point scanning microscopes [Invited].
The performance of fluorescence microscopy and nanoscopy is often discussed by the effective point spread function and the optical transfer function. However, due to the complexity of the fluorophore properties such as photobleaching or other forms of photoswitching, which introduce a variance in photon emission, it is not trivial to choose optimal imaging parameters and to predict the spatial resolution. In this paper, we analytically derive a theoretical framework for estimating the achievable resolution of a microscope depending on parameters such as photoswitching, labeling densities, exposure time and sampling. We developed a numerical simulation software to analyze the impact of reversibly switchable probes in RESOLFT imaging.


Screening of human tumor antigens for CD4 T cell epitopes by combination of HLA-transgenic mice, recombinant adenovirus and antigen peptide libraries.
As tumor antigen-specific CD4+ T cells can mediate strong therapeutic anti-tumor responses in melanoma patients we set out to establish a comprehensive screening strategy for the identification of tumor-specific CD4+ T cell epitopes suitable for detection, isolation and expansion of tumor-reactive T cells from patients. To scan the human melanoma differentiation antigens TRP-1 and TRP-2 for HLA-DRB1*0301-restricted CD4+ T cell epitopes we applied the following methodology: Splenocytes of HLA-DRB1*0301-transgenic mice immunized with recombinant adenovirus encoding TRP-1 (Ad5.TRP-1) or TRP-2 (Ad5.TRP-2) were tested for their T cell reactivity against combinatorial TRP-1- and TRP-2-specific peptide libraries. CD4+ T cell epitopes thus identified were validated in the human system by stimulation of peripheral blood mononuclear cells (PBMC) from healthy donors and melanoma patients. Using this strategy we observed that recombinant Ad5 induced strong CD4+ T cell responses against the heterologous tumor antigens. In Ad5.TRP-2-immunized mice CD4+ T cell reactivity was detected against the known HLA-DRB1*0301-restricted TRP-2(60-74) epitope and against the new epitope TRP-2(149-163). Importantly, human T cells specifically recognizing target cells loaded with the TRP-2(149-163)-containing library peptide or infected with Ad5.TRP-2 were obtained from healthy individuals, and short term in vitro stimulation of PBMC revealed the presence of epitope-reactive CD4+ T cells in melanoma patients. Similarly, immunization of mice with Ad5.TRP-1 induced CD4+ T cell responses against TRP-1-derived peptides that turned out to be recognized also by human T cells, resulting in the identification of TRP-1(284-298) as a new HLA-DRB1*0301-restricted CD4+ T cell epitope. Our screening approach identified new HLA-DRB1*0301-restricted CD4+ T cell epitopes derived from melanoma antigens. This strategy is generally applicable to target antigens of other tumor entities and to different HLA class II molecules even without prior characterization of their peptide binding motives.


Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder.
Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.


Predictive Radiation Oncology - A New NCI-DOE Scientific Space and Community.
With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops-and a final concluding "World Café" on March 29, 2021-focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, and 27 universities. Here we summarize the workshops by first describing the background for the workshops. Participants identified twelve key questions-and collaborative parallel ideas-as the focus of work going forward to advance the field. These were then used to define short-term and longer-term "Blue Sky" goals. In addition, the group determined key success factors for predictive oncology in the context of radiation oncology, if not the future of all of medicine. These are: cross-discipline collaboration, targeted talent development, development of mechanistic mathematical and computational models and tools, and access to high-quality multiscale data that bridges mechanisms to phenotype. The workshop participants reported feeling energized and highly motivated to pursue next steps together to address the unmet needs in radiation oncology specifically and in cancer research generally and that NCI and DOE project goals align at the convergence of radiation therapy and advanced computing.


Management of a Brain Abscess Presumably Caused by Radiation Osteomyelitis of the Mandible.
In this clinical report, we present the management of a brain abscess that was presumed to be caused by radiation osteomyelitis of the mandible. The patient underwent chemoradiotherapy for oropharyngeal carcinoma on the left side at the Department of Otolaryngology of our hospital in 2000. Local recurrence or metastasis did not occur post-treatment. In January 2009, the patient was diagnosed with radiation osteomyelitis of the mandible on the left side, complicated by a pathologic fracture. In July 2011, numbness occurred in the left upper extremity and the patient was transferred to the emergency center of our hospital. A computed tomography scan showed a tumor lesion in the brain that was diagnosed as a brain abscess by magnetic resonance imaging. Neurosurgeons performed burr hole drainage of the abscess, followed by administration of antibiotics. Although impaired fine movements of the left hand remain, progress has been relatively favorable with no recurrence of osteomyelitis or brain abscess post-surgery.


Distracting effects in length matching.
In psychophysical experiments, subjects matched two spatial intervals of a three-spot stimulus into what appeared to them to be equal. The stimulus was flanked by stripes. The length matching errors increased in proportion to the referent interval of the stimulus and approached 6-12 percent of its length. Also, the error increased with an increase of the width of the gaps between the spots and the distracting stripes. Error reached a maximum at gaps equal to 10-15 percent of the length of the referent interval of the stimulus. When the luminance of the stripes increased or decreased, in comparison to the luminance of the background, length matching errors grew symmetrically and became approximately constant at higher contrasts. The experimental findings show the presence of local positional averaging which may be described quantitatively by means of spatial filtering procedures.


[A survey on sex knowledge and medical demand of the cases in Kaohsiung city adolescent health clinic].
The purpose of this survey is to study the sex knowledge of adolescents, and to analyze their need in sex consultation and related health problem in Kaohsiung city. A total of 1,000 study subjects were recruited from May 1991 to May 1994. A self-administered questionnaire and medical records were used to obtain related information. The results were as follows: 1. The male to female ratio of study subjects was 1:2. Half of them were students, 44.1% had sexual experience, and the mean +/- standard deviation of age at first sex experience was 19.1 +/- 2.8 years. 2. The average percentage of correct knowledge was as low as 67.6%. It indicated an inadequacy of sex knowledge in adolescents. Females had better knowledge than males. Subjects who had graduated from senior high schools had better knowledge than those graduated from middle schools. No association was found between the score of sex knowledge and occupation. 3. 12.5% of study subjects believed that "masturbation" might cause neurasthenia, kidney malfunction and loss of memory, while 11.9% recognized that "nocturnal emission" might result in abnormal ejaculation, mental aberration and guilty feelings. Furthermore, 3.8% considered that kissing, hugging or sleeping together might cause pregnancy. 4. Most adolescents felt that "guidance on sex knowledge" was the major reason for them to visit the adolescent clinic and "obstetric and gynecological problems" was the second most important. 5. Males and females have the same prevalence of sex experience, and 50.6% of them did not practice contraception. 88.9% subjects had a high risk of getting pregnancy. 6. Males had a higher percentage of more than one heterosexual partner than females did. There was a higher percentage of people with a high education level having a fixed heterosexual partner than that of those with a low education level.


The use of enriched 6Li and 7Li Lif:Mg,Cu,P glass-rod thermoluminescent dosemeters for linear accelerator out-of-field radiation dose measurements.
(6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescent dosemeters (TLDs) were used for measurements of out-of-field photon and neutron doses produced by Varian iX linear accelerator. Both TLDs were calibrated using 18-MV X-ray beam to investigate their dose-response sensitivity and linearity. CR-39 etch-track detectors (Luxel+, Landauer) were employed to provide neutron dose data to calibrate (6)LiF:Mg,Cu,P TLDs at various distances from the isocentre. With cadmium filters employed, slow neutrons (<0.5 eV) were distinguished from fast neutrons. The average in-air photon dose equivalents per monitor unit (MU) ranged from 1.5±0.4 to 215.5±94.6 μSv at 100 and 15 cm from the isocentre, respectively. Based on the cross-calibration factors obtained with CR-39 etch-track detectors, the average in-air fast neutron dose equivalents per MU range from 10.6±3.8 to 59.1±49.9 μSv at 100 and 15 cm from the isocentre, respectively. Contribution of thermal neutrons to total neutron dose equivalent was small: 3.1±7.2 μSv per MU at 15 cm from the isocentre.


Current attitudes toward, and incidence of, sterilization of cats and dogs by caregivers (owners) in Auckland, New Zealand.
This study distributed a questionnaire to cat or dog caregivers (owners) throughout Auckland, New Zealand, to investigate the attitudes of human companions toward the sterilization of their cats and dogs and the degree to which this occurs relative to demographic information gathered. A total of 276 recipients returned questionnaires with data pertinent to 477 cats and dogs. Female owners were more likely than were males to sterilize cats or dogs: 90.2% sterilization rate compared with 80%. Statistical trends also suggested that owners with a postschool education had a higher percentage of sterilized nonhuman animals than owners with no postschool or only school-age education. Cats were more likely than dogs to be neutered: 91.7% versus 78.5%. Companion animals not annually vaccinated were more likely to be sterilized than animals who were vaccinated annually: 93.6% and 85.4%. The study also showed gender bias and age differences in owner attitudes toward a number of the statements regarding sterilization, with male owners more likely to be concerned about the effect of neutering or spaying on the sexuality or masculinity of the animal.


Phase behavior of ABC cyclic terpolymer melts: a simulation study.
The phase behavior of ABC cyclic terpolymer melts is investigated using a simulated annealing technique. A ternary phase diagram is constructed by tuning the volume fractions of the three blocks (fA, fB, and fC) in the case of symmetric interactions. 11 phases are predicted, including lamellae with spheres at the interfaces, lamellae with spheres inside a domain, lamellae with spheres inside domains, cylinders in perforated lamellae, [6.6.6] tiling patterns, lamella + cylinder, hierarchical double-gyroid, columnar piled disk, patched spheres, cylinders with spheres at the interfaces and double gyroid with spheres at the interfaces. In these structures, the end segments of the three blocks tend to distribute uniformly on the A/B, B/C, or A/C interfaces, which may result in superior mechanical properties of the structures in cyclic terpolymer systems than those of the same structures formed in star or linear terpolymer systems. The physical reason for the similarities and differences between the phases formed in ABC cyclic and star terpolymer systems is investigated. Our simulation results are compared with related experimental observations and theoretical calculations.


Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients.
Awareness with explicit recall of intra-operative events is a rare and distressing complication that may lead to severe psychological symptoms. Candidate depth of anesthesia monitors have been developed, partly with the aim of preventing this complication. Despite conflicting results from clinical trials and the lack of incisive validation, such monitors have enjoyed widespread clinical adoption, in particular the bispectral index. The American Society of Anesthesiologists has called for adequately powered and rigorously designed clinical trials to determine whether the use of such monitors decreases the incidence of awareness in various settings. The aim of this study is to determine with increased precision whether incorporating the bispectral index into a structured general anesthesia protocol decreases the incidence of awareness with explicit recall among a subset of surgical patients at increased risk for awareness and scheduled to receive an inhalation gas-based general anesthetic. BAG-RECALL is a multi-center, randomized, controlled clinical trial, in which 6,000 patients are being assigned to bispectral index-guided anesthesia (target range, 40 to 60) or end-tidal anesthetic gas-guided anesthesia (target range, 0.7 to 1.3 age-adjusted minimum alveolar concentration). Postoperatively, patients are being assessed for explicit recall at two intervals (0 to 72 hours, and 30 days after extubation). The primary outcome of the trial is awareness with explicit recall. Secondary outcomes include postoperative mortality, psychological symptoms, intensive care and hospital length of stay, average anesthetic gas administration, postoperative pain and nausea and vomiting, duration of stay in the recovery area, intra-operative dreaming, and postoperative delirium. This trial has been designed to complement two other clinical trials: B-Unaware and MACS (ClinicalTrials.gov numbers, NCT00281489 and NCT00689091). With the large patient numbers and complementary rigorous designs, it is envisaged that pre-specified meta-analyses will address some of the outstanding controversies and questions relating to processed electroencephalography monitoring. ClinicalTrials.gov Identifier: NCT00682825.


Sustained inhibitory actions of a potent antagonist of gonadotropin-releasing hormone in postmenopausal women.
The inhibitory time course and dose-related characteristics of a new potent GnRH antagonist peptide, [N-acetyl-D-pCl-Phe1,2-D-Trp3-D-Lys6-D-Ala10]GnRH, on gonadotropin secretion were studied in nine postmenopausal women. Effective suppression of gonadotropin secretion was correlated with increased circulating concentrations of immunoassayable GnRH antagonist. Inhibition of gonadotropin secretion was achieved by a parenteral dose of 300 micrograms/kg GnRH antagonist. This dose reduced plasma bioactive LH concentrations by 49-59%, immunoactive LH by 41-46%, and immunoactive FSH by 25-40%. Blockade of gonadotropin secretion was sustained for 10-28 h after a single injection of the synthetic decapeptide. This prolonged action was associated with significant plasma protein binding of the GnRH antagonist and mean plasma half-times of disappearance of 1.5 and 21 h for the fast and slow components, respectively. In summary, we have described the biological actions of a potent GnRH antagonist that binds avidly to serum proteins, has a prolonged plasma residence time, and exerts sustained inhibitory effects on bio- and immunoactive LH release in man. The extended duration of action of this compound may reflect in part its significant binding to circulating plasma proteins.


Citicoline induces angiogenesis improving survival of vascular/human brain microvessel endothelial cells through pathways involving ERK1/2 and insulin receptor substrate-1.
Citicoline is one of the neuroprotective agents that have been used as a therapy in stroke patients. There is limited published data describing the mechanisms through which it acts. We used in vitro angiogenesis assays: migration, proliferation, differentiation into tube-like structures in Matrigel™ and spheroid development assays in human brain microvessel endothelial cells (hCMEC/D3). Western blotting was performed on protein extraction from hCMEC/D3 stimulated with citicoline. An analysis of citicoline signalling pathways was previously studied using a Kinexus phospho-protein screening array. A staurosporin/calcium ionophore-induced apoptosis assay was performed by seeding hCMEC/D3 on to glass coverslips in serum poor medium. In a pilot in vivo study, transient MCAO in rats was carried out with and without citicoline treatment (1000 mg/Kg) applied at the time of occlusion and subsequently every 3 days until euthanasia (21 days). Vascularity of the stroke-affected regions was examined by immunohistochemistry. Citicoline presented no mitogenic and chemotactic effects on hCMEC/D3; however, it significantly increased wound recovery, the formation of tube-like structures in Matrigel™ and enhanced spheroid development and sprouting. Citicoline induced the expression of phospho-extracellular-signal regulated kinase (ERK)-1/2. Kinexus assays showed an over-expression of insulin receptor substrate-1 (IRS-1). Knock-down of IRS-1 with targeted siRNA in our hCMEC/D3 inhibited the pro-angiogenic effects of citicoline. The percentage of surviving cells was higher in the presence of citicoline. Citicoline treatment significantly increased the numbers of new, active CD105-positive microvessels following MCAO. The findings demonstrate both a pro-angiogenic and protective effect of citicoline on hCMEC/D3 in vitro and following middle cerebral artery occlusion (MCAO) in vivo.


Basic Surveillance Network, a European database for surveillance data on infectious diseases.
The Basic Surveillance Network was started in 2000 and is one of the networks on infectious diseases funded by the European Commission. The network collects and makes readily available basic surveillance data on infectious diseases from all the 'old' (pre-2004) European Union member states. The aim is to provide easy access to descriptive data that already exist in national databases, so that it is possible to monitor and compare incidence trends for infectious diseases in the EU member states. The list of diseases covered by the network has recently been expanded from 10 initial 'pilot' diseases to over 40 diseases listed by the EU to be under surveillance. In the near future, the new member states will be invited to participate in the network. Data are case-based and comprise date of onset of disease, age and sex. Only a very short list of disease specific additional variables, such as country of infection or immunisation status, is collected. Classification of cases (possible, probable, confirmed) is specified according to EU case definitions. The participants of the network have access to an internal web site were all the data is presented in tables and graphs. An open website is available for the public at https://www.eubsn.org./BSN/


Whole genome comparison of six Crocosphaera watsonii strains with differing phenotypes.
Crocosphaera watsonii, a unicellular nitrogen-fixing cyanobacterium found in oligotrophic oceans, is important in marine carbon and nitrogen cycles. Isolates of C. watsonii can be separated into at least two phenotypes with environmentally important differences, indicating possibly distinct ecological roles and niches. To better understand the evolutionary history and variation in metabolic capabilities among strains and phenotypes, this study compared the genomes of six C. watsonii strains, three from each phenotypic group, which had been isolated over several decades from multiple ocean basins. While a substantial portion of each genome was nearly identical to sequences in the other strains, a few regions were identified as specific to each strain and phenotype, some of which help explain observed phenotypic features. Overall, the small-cell type strains had smaller genomes and a relative loss of genetic capabilities, while the large-cell type strains were characterized by larger genomes, some genetic redundancy, and potentially increased adaptations to iron and phosphorus limitation. As such, strains with shared phenotypes were evolutionarily more closely related than those with the opposite phenotype, regardless of isolation location or date. Unexpectedly, the genome of the type-strain for the species, C. watsonii WH8501, was quite unusual even among strains with a shared phenotype, indicating it may not be an ideal representative of the species. The genome sequences and analyses reported in this study will be important for future investigations of the proposed differences in adaptation of the two phenotypes to nutrient limitation, and to identify phenotype-specific distributions in natural Crocosphaera populations.


Objective evaluation of the sweet spot size in spatial sound reproduction using elevated loudspeakers.
In a previous study, three crosstalk cancellation techniques were evaluated and compared under different conditions. Least-squares approximations in the frequency and time domain were evaluated along with a method based on minimum-phase decomposition and a frequency independent delay. In general, the least-squares methods outperformed the method based on the minimum-phase decomposition. However, the evaluation was only done for the best-case scenario, where the transfer functions used to design the filters correspond to the listener's transfer functions and his/her location and orientation relative to the loudspeakers. This paper presents a follow-up evaluation of the performance of the three inversion techniques when the above mentioned conditions are relaxed. A setup to measure the sweet spot of different loudspeaker arrangements is described. The sweet spot was measured for 21 different loudspeaker configurations, including two- and four-channel setups. Lateral and frontal displacement were measured along with head rotations. The setups were evaluated at different elevation angles. The results suggest that when the loudspeakers are placed at elevated positions, a wider effective area is obtained. Additionally, the two-channel configurations showed to be more robust to head misalignments than the four-channel configurations.


Jejunostomy feeding for the conservative management of spontaneous rupture of the oesophagus.
Three patients with spontaneous rupture of the oesophagus (Boerhaave's syndrome) were successfully treated by a conservative regimen consisting of nil orally and broad-spectrum antibiotics, while their nutrition was satisfactorily maintained by jejunostomy feeding. Such a regimen is simpler and cheaper than one utilising parenteral nutrition: it avoids its complications and limitations, and will enable healing to take place within three weeks after the rupture has occurred. It is therefore suggested that the conservative management of Boerhaave's syndrome is the treatment of choice.


The distribution of lipid attached spin probes in bilayers: application to membrane protein topology.
The distribution of the lipid-attached doxyl electron paramagnetic resonance (EPR) spin label in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes has been studied by (1)H and (13)C magic angle spinning nuclear magnetic resonance relaxation measurements. The doxyl spin label was covalently attached to the 5th, 10th, and 16th carbons of the sn-2 stearic acid chain of a 1-palmitoyl-2-stearoyl-(5/10/16-doxyl)-sn-glycero-3-phosphocholine analog. Due to the unpaired electron of the spin label, (1)H and (13)C lipid relaxation rates are enhanced by paramagnetic relaxation. For all lipid segments the influence of paramagnetic relaxation is observed even at low probe concentrations. Paramagnetic relaxation rates provide a measure for the interaction strength between lipid segments and the doxyl group. Plotted along the membrane director a transverse distribution profile of the EPR probe is obtained. The chain-attached spin labels are broadly distributed in the membrane with a maximum at the approximate chain position of the probe. Both (1)H and (13)C relaxation measurements show these broad distributions of the doxyl group in the membrane indicating that (1)H spin diffusion does not influence the relaxation measurements. The broad distributions of the EPR label result from the high degree of mobility and structural heterogeneity in liquid-crystalline membranes. Knowing the distribution profiles of the EPR probes, their influence on relaxation behavior of membrane inserted peptide and protein segments can be studied by (13)C magic angle spinning nuclear magnetic resonance. As an example, the location of Ala residues positioned at three sites of the transmembrane WALP-16 peptide was investigated. All three doxyl-labeled phospholipid analogs induce paramagnetic relaxation of the respective Ala site. However, for well ordered secondary structures the strongest relaxation enhancement is observed for that doxyl group in the closest proximity to the respective Ala. Thus, this approach allows study of membrane insertion of protein segments with respect to the high molecular mobility in liquid-crystalline membranes.


Hepatitis C virus impairs natural killer cell activity via viral serine protease NS3.
Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection. To investigate the role of HCV nonstructural proteins especially NS3 in the impairment of NK functions, NK cells were isolated from the PBMCs by negative selection. To assess the direct cytotoxicity and IFN-γ production capability of NK cells, co-cultured with uninfected, HCV-infected, HCV-NS3 DNA-transfected Huh-7.5, or HCV-NS replicon cells. To determine the effect of an NS3 serine protease inhibitor, HCV-infected Huh-7.5 cells were treated with BILN-2061. Then, NK cells were harvested and further co-cultured with K-562 target cells. NK cell functions were analyzed by flow cytometry and enzyme-linked immunosorbent assay. When co-cultured with HCV-infected Huh-7.5 cells, the natural cytotoxicity and IFN-γ production capability of NK cells were significantly reduced. NK cell functions were inhibited to similar levels upon co-culture with HCV-NS replicon cells, NS3-transfected cells, and HCV-infected Huh-7.5 cells. These reductions were restored by BILN-2061-treatment. Furthermore, BILN-2061-treatment significantly increased degranulation against K-562 target cells and IFN-γ productivity in NK cells. Consistent with these findings, the expression levels of activating NK cell receptors, such as NKp46 and NKp30, were also increased. In HCV-infected cells, the serine protease NS3 may play a role in the abrogation of NK cell functions in the early phase of infection through downregulation of NKp46 and NKp30 receptors on NK cells. Together, these results suggest that NS3 represents a novel drug target for the treatment of HCV infections.


Remote sensing of the magnetic moment of uranus: predictions for voyager.
Power is supplied to a planet's magnetosphere from the kinetic energy of planetary spin and the energy flux of the impinging solar wind. A fraction of this power is available to drive numerous observable phenomena, such as polar auroras and planetary radio emissions. In this report our present understanding of these power transfer mechanisms is applied to Uranus to make specific predictions of the detectability of radio and auroral emissions by the planetary radio astronomy (PRA) and ultraviolet spectrometer (UVS) instruments aboard the Voyager spacecraft before its encounter with Uranus at the end of January 1986. The power available for these two phenomena is (among other factors) a function of the magnetic moment of Uranus. The date of earliest detectability also depends on whether the predominant power source for the magnetosphere is planetary spin or solar wind. The magnetic moment of Uranus is derived for each power source as a function of the date of first detection of radio emissions by the PRA instrument or auroral emissions by the UVS instrument. If we accept the interpretation of ultraviolet observations now available from the Earth-orbiting International Ultraviolet Explorer satellite, Uranus has a surface magnetic field of at least 0.6 gauss, and more probably several gauss, making it the largest or second-largest planetary magnetic field in the solar system.


Fatal cyclobenzaprine overdose with postmortem values.
There are only two published cases of overdose with postmortem blood cyclobenzaprine concentrations, both with confounding factors. We report two additional cases of fatal cyclobenzaprine overdose with postmortem values. Case 1: a 56-year-old female was found in full cardiopulmonary arrest after a verbal suicide threat to a friend. Postmortem blood concentrations were cyclobenzaprine 0.96 mg/L and diazepam 0.3 mg/L. Case 2: a 37-year-old male was found in full arrest by a family member after an intentional ingestion of cyclobenzaprine. Postmortem blood concentrations were cyclobenzaprine 0.8 mg/L and ethanol 0.174 gm/dL. The concentrations of diazepam and ethanol reported in these two patients were not found in quantities usually associated with a fatal outcome, suggesting that the cyclobenzaprine was the primary cause of the fatality. Additionally, the blood was drawn from a femoral site, so that postmortem redistribution is not a likely factor. Blood concentration of > or = 0.8 mg/L cyclobenzaprine may be associated with a fatal outcome.


Preoperative evaluation and a risk assessment in patients undergoing abdominal surgery.
Patients who undergo abdominal surgery present along a variable spectrum of health. This ranges from the healthy young patient undergoing elective hemorrhoid surgery to the octogenarian in unstable health with multiple comorbidities. Regardless of a patient's current state of health, a preoperative assessment is crucial in planning the operative approach and in recognizing the possible postoperative complications for the implementation of a proper intervention if necessary. A broad evaluation of the patient includes identifying conditions that may predispose the patient to risks and the complications not directly related to the surgical procedure. The purpose of this article is to review the preoperative assessment in patients undergoing simple to complex procedures. The article provides general guidelines for the preoperative workup, which should be individualized for each patient, and the planned procedure, with the goal of reducing the postoperative complications. Risk stratification depends on a patient's condition and the extension of the planned surgical approach. It may also help to improve the postoperative outcome. A further preoperative workup should be individualized and tailored to the complexity of each case.


Low- and high-testosterone individuals exhibit decreased aversion to economic risk.
Testosterone is positively associated with risk-taking behavior in social domains (e.g., crime, physical aggression). However, the scant research linking testosterone to economic risk preferences presents inconsistent findings. We examined the relationship between endogenous testosterone and individuals' economic preferences (i.e., risk preference, ambiguity preference, and loss aversion) in a large sample (N = 298) of men and women. We found that endogenous testosterone levels have a significant U-shaped association with individuals' risk and ambiguity preferences, but not loss aversion. Specifically, individuals with low or high levels of testosterone (more than 1.5 SD from the mean for their gender) were risk and ambiguity neutral, whereas individuals with intermediate levels of testosterone were risk and ambiguity averse. This relationship was highly similar in men and women. In contrast to received wisdom regarding testosterone and risk, the present data provide the first robust evidence for a nonlinear association between economic preferences and levels of endogenous testosterone.


Behavioral economic insights to improve medication adherence in adults with chronic conditions: a scoping review protocol.
The objective of this review is to map the evidence on the use of behavioral economic insights to improve medication adherence in adults with chronic conditions. Medication non-adherence is a barrier to effectively managing chronic conditions, leading to poorer patient outcomes and placing an additional financial burden on healthcare systems. As the population ages and the prevalence of chronic disease increases, new ways to influence patient behavior are needed. Approaches that use insights from behavioral economics may help improve medication adherence, thus reducing morbidity, mortality and financial costs of unmanaged chronic diseases. Eligible studies will include adults taking medication for a chronic condition. All interventions relevant to high-income settings using insights from behavioral economics to improve medication adherence in adults will be considered. Contexts may include, but are not limited to, primary health care, corporate wellness programs and health insurance schemes. Any study design published in English will be considered. Studies in facilities where medication is administered to patients will be excluded. PubMed, Embase, Scopus, PsycINFO, EconLit and CINAHL will be searched from database inception to present. Gray literature will be searched using Google Scholar, OpenGrey and the Grey Literature Report. One reviewer will review titles, and then two reviewers will independently review abstracts to identify eligible studies. One reviewer will extract data on study characteristics, study design and study outcomes. A second reviewer will validate 25% of the extracted information. The results of the data extraction will be presented in a table, and a narrative summary will be presented.


The high prevalence of pre-existing mental health complaints in clients attending Saint Mary's Sexual Assault Referral Centre: Implications for initial management and engagement with the Independent Sexual Violence Advisor service at the centre.
The Saint Mary's Sexual Assault Referral Centre has a unique service delivery model whereby it provides an integrated physical and psychological support services to clients, women men and children, living in Greater Manchester. The service is available to those who have reported rape or sexual assault, whether this is recent or historic. Clients living in surrounding areas of Cheshire are provided with forensic and medical services at Saint Mary's Centre, with follow-up care provided locally, as appropriate. The primary objective was to identify the prevalence of self-reported pre-existing mental health complaints amongst adult clients who attended Saint Mary's Centre for a forensic medical examination. The secondary objective was to consider levels of engagement with the Centre's Independent Sexual Violence Advisor service by comparing clients who reported a mental health complaint to clients who did not. One-hundred and eighty sets of client's notes from 2016 were retrospectively analysed. Client inclusion criteria were that they were (a) over the age of 18 years when attending the Centre, (b) had attended for a forensic medical examination. 69% of clients analysed reported a pre-existing mental health complaint. The time taken for clients to present to Saint Mary's Centre following a reported assault tended to be later for the clients with self-reported mental health problems than those without. However, there was no difference in the long-term engagement with the Centre's Independent Sexual Violence Advisor service at the Centre between the two groups. Prevalence of self-reported pre-existing mental health complaints is extremely high in clients presenting at Saint Mary's Centre as compared to national and regional prevalence rates for mental health complaints in the general population. The vulnerability of this client group should be considered when they attend a SARC and support provided should be appropriate and accessible to their needs. Staff should have adequate training and supervision to be able to respond in this way.


[From Adam to ecstacy; legal use of MDMA in the 1970s and 1980s].
MDMA is currently a controversial psychedelic in the Netherlands: it is banned under the Opium Act, but widely used as a recreational drug. According to the government, the normalization of MDMA must be combated, others argue in favour of legalization. Meanwhile, in recent years psychiatry has become interested in renewed therapeutic use of MDMA.
 AIM: To place the current discussion of MDMA in the context of recent history. What can we learn from the way MDMA was used in America and Western Europe in the period between the (re)discovery of the drug in the 1970s and its legal prohibition in the 1980s?
 METHOD: Survey of the literature on the history of MDMA, and additional source research.
 CONCLUSION: In the period before MDMA became illegal, its use was closely linked to the pursuit of self-actualisation in therapeutic, spiritual and recreational contexts. History shows that the meaning that people attach to a psychoactive substance like MDMA is highly dependent on the context of use. Like all drugs, MDMA also has multiple functionalities and 'framings'. The psychoactive substance cannot be reduced to one valuation or essence.


CPHmodels-3.0--remote homology modeling using structure-guided sequence profiles.
CPHmodels-3.0 is a web server predicting protein 3D structure by use of single template homology modeling. The server employs a hybrid of the scoring functions of CPHmodels-2.0 and a novel remote homology-modeling algorithm. A query sequence is first attempted modeled using the fast CPHmodels-2.0 profile-profile scoring function suitable for close homology modeling. The new computational costly remote homology-modeling algorithm is only engaged provided that no suitable PDB template is identified in the initial search. CPHmodels-3.0 was benchmarked in the CASP8 competition and produced models for 94% of the targets (117 out of 128), 74% were predicted as high reliability models (87 out of 117). These achieved an average RMSD of 4.6 A when superimposed to the 3D structure. The remaining 26% low reliably models (30 out of 117) could superimpose to the true 3D structure with an average RMSD of 9.3 A. These performance values place the CPHmodels-3.0 method in the group of high performing 3D prediction tools. Beside its accuracy, one of the important features of the method is its speed. For most queries, the response time of the server is <20 min. The web server is available at http://www.cbs.dtu.dk/services/CPHmodels/.


Vascular effects of FGF-2 and VEGF-B in rabbits with bilateral hind limb ischemia.
To assess fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-B (VEGF-B) effects on flow reserve and morphological adaptation in the rabbit ischemic hind limb. Following bilateral femoral artery ligation, calf blood pressure (C(BP)), flow reserve, collateral artery numbers and capillary numbers were assessed. Treatment consisted of rabbit serum albumin (RSA), FGF-2, VEGF-B or FGF-2 + VEGF-B. Ligation decreased C(BP); on day 14, a 48% deficit remained in the RSA group compared with a deficit of only 22% in FGF-2 and VEGF-B groups. On day 3, flow reserve was attenuated 60%, but recovered by day 14 (with no treatment effects). Collateral artery numbers increased with RSA (+28%), FGF-2 (+53%), VEGF-B (+47%) and FGF-2 + VEGF-B (+59%). Rectus femoris muscle total capillary profiles and fibers per cross-section were alike across groups. Tibialis anterior muscle cross-sectional area was lower with ligation and total capillary number was less in RSA and FGF-2 groups, providing evidence for angiogenesis with VEGF-B. Capillary/muscle fiber ratio was similar in each group. FGF-2 and VEGF-B enhanced lower limb perfusion as indicated by improved C(BP) and combined treatment increased collateral artery number. Flow reserve recovery was not enhanced by cytokine treatment. VEGF-B, but not FGF-2, caused angiogenesis in the tibialis anterior muscle. Overall, VEGF-B may have advantages over FGF-2 in this setting; however, their combination may further improve arteriogenesis.


Veterans' experience in using the online Surgeon General's family health history tool.
AIM: To assess veterans' experience and satisfaction in using the Surgeon General's (SG) online family health history (FHH) tool, and determine the perceived facilitators and barriers to using the online SG-FHH tool. MATERIALS #ENTITYSTARTX00026; METHODS: A mixed-method using both qualitative and quantitative approaches was employed in this study. A total of 35 veterans at the VA Medical Center in San Antonio, Texas, USA were invited to enter their FHH information using the online SG-FHH tool, complete the study's satisfaction survey and participate in a short semi-structured interview. The goal of the semi-structured interviews was to assess participants perceived facilitators and barriers to using the online SG-FHH tool. All participants were also provided with a printed copy of their pedigree, which was generated by the SG-FHH tool and were encouraged to share it with their relatives and providers. RESULTS: The majority of participants (91%) said that they had access to a computer with internet capability and 77% reported that they knew how to use a computer. More than two-thirds of the participants felt that items on the SG-FHH tool were easy to read and felt that FHH categories were relevant to their family's health. Approximately 94% of participants viewed the SG-FHH tool as useful, and the majority of participants (97%) indicated that they were likely to recommend the tool to others. Content analysis of the semi-structured interviews highlighted several barriers to veterans' use of the SG-FHH tool and their FHH information. These included: lack of patients' knowledge regarding their relatives' FHH, and privacy and confidentiality concerns. CONCLUSION: This study provides information on the performance and functionality of an inexpensive and widely accessible method for FHH collection. Furthermore, our findings highlight several opportunities and challenges facing the utilization of FHH information as a clinical and genomic tool at the Veterans Health Administration (VHA). The results suggest that strategies that improve veterans' knowledge regarding the importance of their FHH information and that address their concerns about privacy and confidentiality may enhance the successful implementation of FHH information into VHA clinical practice. IMPLICATIONS: identifying a locally accepted method for FHH collection and documentation which can be conducted outside of the patient visit will reduce time burdens for providers and patients and allow for a focus on other important topics during clinic visits. Improvement in familial risk screening and assessment will enable the VHA to be prepared for personalized medicine and focus their resources on promoting critically important health behaviors for populations with the highest risk of developing chronic diseases and their complications.


Assessment of injury to the thoracolumbar posterior ligamentous complex in the setting of normal-appearing plain radiography.
The posterior ligamentous complex (PLC) is thought to contribute significantly to the stability of thoracolumbar spine. Obvious translation or dislocation of an interspace clearly denotes injury to the PLC. A recent survey of the Spine Trauma Study Group indicated that plain radiographic findings, if present, are most helpful in determining PLC injury. However, confusion exists when plain radiography shows injury to the anterior spinal column without significant kyphosis or widening of the posterior interspinous space. The objective of this study is to identify imaging parameters that may suggest a disruption of the posterior ligamentous complex of the thoracolumbar spine in the setting of normal-appearing plain radiographs. This study was performed, in part, as a pilot study to determine critical imaging parameters to be included in a future prospective, randomized, multicenter study. Survey analysis of the Spine Trauma Study Group. None. Compilation and statistical analysis of survey results. Based on a systematic review of the English literature from 1949 to present, we identified a series of traits not found on plain X-rays that were consistent with PLC injury. This included five imaging findings on either computed tomography (CT) scans or magnetic resonance imaging (MRI) and several physical examination features. These items were placed on a survey and sent to the members of the Spine Trauma Study Group. They were asked to rank the items from most important to least important in representing an injury to the PLC in the setting of normal-appearing plain radiographs. Thirty-three of 47 surveys were returned for final analysis. Thirty-nine percent (13/33) of the members ranked "disrupted PLC components (i.e., interspinous ligament, supraspinous ligament, ligamentum flavum) on T1 sagittal MRI" as the most important factor in determining disruption of PLC. When analyzed with a point-weighted system, "diastasis of the facet joints on CT" received the most points, indicating that this category was ranked high by the majority of the members of the group. The members were also given freedom to add other criteria that they believed were important in determining PLC integrity in the setting of normal-appearing plain radiograph. Of the other criteria suggested, one included a physical finding and the other a variant of MR sequencing. In a setting of normal-appearing plain radiographs, PLC injury as displayed on T1-weighted MRI and diastasis of the facet joints on CT scan seem to be the most popular determinants of probable PLC injury among members of the Spine Trauma Study Group. Between MRI and CT scan, most members feel that various characteristics on MRI studies were more helpful.


Gender-specific differences in hypothalamus-pituitary-adrenal axis activity during childhood: a systematic review and meta-analysis.
Gender-specific differences in hypothalamus-pituitary-adrenal (HPA) axis activity have been postulated to emerge during puberty. We conducted a systematic review and meta-analysis to test the hypothesis that gender-specific differences in HPA axis activity are already present in childhood. From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed non-stimulated cortisol in serum or saliva or cortisol in 24-h urine in healthy males and females aged ≤18 years. Studies that conform with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement were reported. Standardized mean differences (95% CIs) were calculated and analyzed using fixed-effect meta-analysis stratified for age: <8 years (prepubertal) and 8-18 years (peri-/postpubertal). For comparison, we ran the same analyses using random-effects models. Two independent assessors selected 413 out of 6158 records (7%) for full-text screening, of which 79 articles were included. Of these, 58 (with data on 16,551 subjects) were included in the meta-analysis. Gender differences in cortisol metabolism differed per age group. Boys aged <8 years had 0.18 (0.06; 0.30) nmol/L higher serum and 0.21 (0.05; 0.37) nmol/L higher salivary cortisol levels, while between 8 and 18 years, boys had 0.34 (0.28; 0.40) nmol/L lower serum and 0.42 (0.38; 0.47) nmol/L lower salivary cortisol levels. In 24-h urine, cortisol was consistently higher in boys, being 0.34 (0.05; 0.64) and 0.32 (0.17; 0.47) μg/24 h higher in the <8- and 8-18-year groups, respectively. However, gender-differences in serum cortisol <8 years and between 8 and 18 years were absent when using random-effects models. Gender differences in cortisol metabolism are already present in childhood, with higher salivary cortisol in boys aged <8 years compared to girls. This pattern was reversed after the age of 8 years. In contrast, the gender-specific difference in cortisol production as assessed through 24-h urine did not change with age. Although differences were small, and analyses of gender differences in serum cortisol were inconclusive, they might contribute to gender-specific origins of health and disease.


Quantitative high throughput screening using a primary human three-dimensional organotypic culture predicts in vivo efficacy.
The tumour microenvironment contributes to cancer metastasis and drug resistance. However, most high throughput screening (HTS) assays for drug discovery use cancer cells grown in monolayers. Here we show that a multilayered culture containing primary human fibroblasts, mesothelial cells and extracellular matrix can be adapted into a reliable 384- and 1,536-multi-well HTS assay that reproduces the human ovarian cancer (OvCa) metastatic microenvironment. We validate the identified inhibitors in secondary in vitro and in vivo biological assays using three OvCa cell lines: HeyA8, SKOV3ip1 and Tyk-nu. The active compounds directly inhibit at least two of the three OvCa functions: adhesion, invasion and growth. In vivo, these compounds prevent OvCa adhesion, invasion and metastasis, and improve survival in mouse models. Collectively, these data indicate that a complex three-dimensional culture of the tumour microenvironment can be adapted for quantitative HTS and may improve the disease relevance of assays used for drug screening.


[Abortive infection in Erwinia carotovora, as a source of nanoparticles of phage nature].
A possibility to obtain nanoparticles of phage nature using abortive phage infection was shown for the first time. It was found out that the nonspecific host Erwinia carotovora subsp. carotovora J2 being infected by phage ZF 40-RT80, the cells form a 100-fold surplus of capsid structures. Using the electron microscope the authors have found two types of phage capsids which differ from each other and have different modal diameters--47.5 and 71.5 nm. The found capsids pack the phage DNA which releases them under treatment of the preparations by DNAse I. A simple method of purification of capsid structures from mature virions which are formed in inconsiderable quantity in the process of abortive phage infection is proposed. The obtained results create preconditions for obtaining capsid nanoparticles as well as for studying the stages of morphogenesis and morphopoiesis of phage ZF40 without attracting special phage mutants.


Primary prevention of sudden cardiac death: indications for cardioverter-defibrillator implantation.
Sudden cardiac death accounts for 400,000 to 450,000 deaths annually in Europe and in the United States. In patients with previous life-threatening arrhythmia, several perspective, randomized, controlled studies have demonstrated that implantable cardioverter-defibrillator (ICD) therapy is superior to the best antiarrhythmic therapy in prolonging survival. Furthermore, in a stratified-risk population with coronary artery disease, left ventricular ejection fraction < or = 35%, non-sustained ventricular arrhythmias, and inducible ventricular tachycardia, the ICD supports the class I level of recommendation by the guidelines published in 1998. The American College of Cardiology, American Heart Association, and North American Society of Pacing and Electrophysiology have updated the 1998 guidelines on the implantation of arrhythmia devices including in a class IIa level of recommendation also patients with a previous Q wave myocardial infarction and left ventricular ejection fraction < or = 30%, independently of their arrhythmic risk profile. In the recent years several randomized studies assessed the role of ICD treatment for primary prevention of sudden cardiac death and total mortality reduction in high-risk groups of patients with ischemic and non-ischemic dilated cardiomyopathy, with special reference to those with heart failure and ventricular dysfunction. This article reviews those trials that have resulted in defining indications for ICD, and that will expand its use in the future.


Little or no residual prostate cancer at radical prostatectomy: vanishing cancer or switched specimen?: a microsatellite analysis of specimen identity.
With more vigilant screening for prostate cancer, there has been an associated increase in patients with little or no residual cancer at radical prostatectomy after an initial diagnosis of minute cancer on needle biopsy. This raises a critical question as to whether the biopsy and subsequent radical prostatectomy in these patients are from the same patient. We used PCR-based microsatellite marker analysis to perform identity test in 46 men (35 with minute cancer and 11 with no residual cancer). Of them, 41 were interpretable, including 31 with minute cancer and 10 with no residual cancer. All 31 interpretable cases with minute cancer showed match between the initial biopsy and radical prostatectomy specimens. Nine of the 10 interpretable cases with no residual cancer showed match and 1 showed mismatch. The remaining 5 cases (4 with minute cancer and 1 with no residual cancer) were considered uninterpretable due to technical problems. The initial biopsy of the mismatched case had high-grade cancer (Gleason score 4 + 4 = 8) measuring 9.6 mm in length with perineural invasion. Our results confirm that, in most cases of "vanishing cancer" in radical prostatectomy specimens, it reflects a chance sampling of a minute cancer and not a switch in specimens. However, specimen switch can rarely occur, and if there is high grade or a lot of cancer on the biopsy with no or very minimal cancer in the radical prostatectomy specimen, one should evaluate for patient identity.


Assessment of hematological indicators, histological alterations, and DNA damage in Danube sturgeon (Acipenser gueldenstaedtii) exposed to the organophosphate malathion.
This study focused on organophosphate malathion toxicity in Danube sturgeon (Acipenser gueldenstaedtii) and its negative effects in sub-lethal concentration. In this context, the LC50 value of fish exposed to five different concentrations and two different sub-lethal concentrations depending on the LC50 value were considered. Accordingly, LC50 of malathion for 96 h was 3.24 mg L-1. In leukocyte (WBC) and hemoglobin (HGB) such as hematological indicators, significant differences were observed in sub-lethal concentration (One-eighth of the LC50 =0.4 mg L-1). In addition, serious histological alterations were observed in the gill and liver tissues after both acute (96 h) and chronic periods (28 days). While epithelial lifting and hyperplasia were the most prominent lesions in the gill, intense vacuolization were observed in the liver. In addition, circulatory disturbances, regressive changes, and progressive changes in the gill and circulatory disturbances and inflammation in the liver were significantly higher for the chronic period. Finally, significantly higher DNA damage was detected in fish exposed malathion in the chronic period compared to the control group. In conclusion, the present study has proven that malathion has a hematological, histological and genotoxic effect on the endangered species A. gueldenstaedtii. Thus, the current study will motivate for residue studies on A. gueldenstaedtii and trigger conservation strategies for local governments.


Rural residents in China are at increased risk of exposure to tick-borne pathogens Anaplasma phagocytophilum and Ehrlichia chaffeensis.
As emerging tick born rickettsial diseases caused by A. phagocytophilum and E. chaffeensis, anaplasmosis and ehrlichiosis have become a serious threat to human and animal health throughout the world. In particular, in China, an unusual transmission of nosocomial cases of human granulocytic anaplasmosis occurred in Anhui Province in 2006 and more recent coinfection case of A. phagocytophilum and E. chaffeensis was documented in Shandong Province. Although the seroprevalence of human granulocytic anaplasmosis (former human granulocytic ehrlichiosis, HGE) has been documented in several studies, these data existed on local investigations, and also little data was reported on the seroprevalence of human monocytic ehrlichiosis (HME) in China. In this cross-sectional epidemiological study, indirect immunofluorescence antibody assay (IFA) proposed by WHO was used to detect A. phagocytophilum and E. chaffeensis IgG antibodies for 7,322 serum samples from agrarian residents from 9 provinces/cities and 819 urban residents from 2 provinces. Our data showed that farmers were at substantially increased risk of exposure. However, even among urban residents, risk was considerable. Seroprevalence of HGA and HME occurred in diverse regions of the country and tended to be the highest in young adults. Many species of ticks were confirmed carrying A. phagocytophilum organisms in China while several kinds of domestic animals including dog, goats, sheep, cattle, horse, wild rabbit, and some small wild rodents were proposed to be the reservoir hosts of A. phagocytophilum. The broad distribution of vector and hosts of the A. phagocytophilum and E. chaffeensis, especially the relationship between the generalized susceptibility of vectors and reservoirs and the severity of the disease's clinical manifestations and the genetic variation of Chinese HGA isolates in China, is urgently needed to be further investigated.


Central processing of pulsed pheromone signals by antennal lobe neurons in the male moth Agrotis segetum.
Male moths use female-produced pheromones as orientation cues during the mate-finding process. In addition to the needs of evaluating the quality and quantity of the pheromone signal, the male moth also needs to resolve the filamentous structure of the pheromone plume to proceed toward the releasing point successfully. To understand how a discontinuous olfactory signal is processed at the central level, we used intracellular recording methods to characterize the response patterns of antennal lobe (AL) neurons to pulsatile stimulation with the full female-produced pheromone blend and its single components in male turnip moths, Agrotis segetum. Air puffs delivered at frequencies of 1, 3, 5, 7, or 10 Hz were used to carry the stimulus. Two types of AL neurons were characterized according to their capabilities to resolve stimulus pulses. The most common type could resolve at least 1-Hz pulses, thus termed fast neurons; another type could not resolve any pulses, thus termed slow neurons. When fast neurons were excited by stimuli, they always displayed biphasic response patterns, a depolarization phase followed by a hyperpolarization phase. This pattern could be evoked by stimulation with both the single pheromone components and the blend. The pulse-resolving capability of the fast neurons correlated significantly with the size of the hyperpolarization phase. When the amplitude was higher and the fall time of the hyperpolarization faster, the neuron could follow more pulses per second. Moreover, interactions between different pheromone components eliciting different response patterns did not improve the pulse-resolving capability of fast neurons.


Promoting mental health among young males in sporting contexts: A systematic review.
Young males experience markedly poorer mental health outcomes. Organised sport settings provide novel prospects to improve the mental health of this subpopulation. This systematic review aimed to evaluate interventions targeted at the promotion of mental health and wellbeing among young males in organised sporting contexts. Six databases (SportDiscus, PsycInfo, Medline, Web of Science, Scopus, CINAHL) were searched from inception to June 2022 (and updated in September 2023). Eligible studies examined interventions targeting the mental health and wellbeing (e.g., depression, anxiety, resilience) or mental health literacy (e.g., stigmatising attitudes, help-seeking) of young males aged 10-24 years (or associated stakeholder samples; e.g., parents or coaches of male youth). A total of 15 studies were included in this review. Overall, the findings indicate promising effects of sport-based interventions on the mental health and mental health literacy outcomes of young males. This review suggests that there is scope to improve the capacity of sports-based interventions to affect positive change in the mental health of male youth. The findings from this review also have important implications for the development and evaluation of sports-based interventions targeted at young males in future.


Relationships between radionuclides, metals, and sediment properties in sediment of a bay exposed to anthropogenic pressure and mixed sediment sources (Kaštela Bay, Adriatic Sea, Croatia).
Natural and anthropogenic radionuclides, metals, organic matter, sediment grain size, mineral composition, and sediment sources were studied in marine sediment of Kaštela Bay up to a depth of 0.5 m. Deposition of man-modified material into the sea was evidenced in sediment mineral composition. Presence of pyrite and hematite in this sediment may pose an environmental concern. Metals, radionuclides, and organic matter were grouped in three groups: (i) variables under no anthropogenic influence and preferentially associated with carbonates (Ca, Sr); (ii) variables under no or weak anthropogenic influence and preferentially associated with aluminosilicates (Al, K, Ti, V, Cr, Mn, Fe, Co, Ni, Ga, Rb, Y, 40K, 232Th); (iii) variables under notable anthropogenic influence and/or natural processes of separation (Cu, Zn, Pb, As, 226Ra, 238U, 137Cs, organic matter). Predominant influencing parameters change with sediment depth for some variables. Anthropogenic influence was the most emphasised for Cu, Zn, and Pb, followed by 137Cs.


Elements of Trust in Digital Health Systems: Scoping Review.
Information and communication technologies have long become prominent components of health systems. Rapid advances in digital technologies and data science over the last few years are predicted to have a vast impact on health care services, configuring a paradigm shift into what is now commonly referred to as digital health. Forecasted to curb rising health costs as well as to improve health system efficiency and safety, digital health success heavily relies on trust from professional end users, administrators, and patients. Yet, what counts as the building blocks of trust in digital health systems has so far remained underexplored. The objective of this study was to analyze what relevant stakeholders consider as enablers and impediments of trust in digital health. We performed a scoping review to map out trust in digital health. To identify relevant digital health studies, we searched 5 electronic databases. Using keywords and Medical Subject Headings, we targeted all relevant studies and set no boundaries for publication year to allow a broad range of studies to be identified. The studies were screened by 2 reviewers after which a predefined data extraction strategy was employed and relevant themes documented. Overall, 278 qualitative, quantitative, mixed-methods, and intervention studies in English, published between 1998 and 2017 and conducted in 40 countries were included in this review. Patients and health care professionals were the two most prominent stakeholders of trust in digital health; a third-health administrators-was substantially less prominent. Our analysis identified cross-cutting personal, institutional, and technological elements of trust that broadly cluster into 16 enablers (altruism, fair data access, ease of use, self-efficacy, sociodemographic factors, recommendation by other users, usefulness, customizable design features, interoperability, privacy, initial face-to-face contact, guidelines for standardized use, stakeholder engagement, improved communication, decreased workloads, and service provider reputation) and 10 impediments (excessive costs, limited accessibility, sociodemographic factors, fear of data exploitation, insufficient training, defective technology, poor information quality, inadequate publicity, time-consuming, and service provider reputation) to trust in digital health. Trust in digital health technologies and services depends on the interplay of a complex set of enablers and impediments. This study is a contribution to ongoing efforts to understand what determines trust in digital health according to different stakeholders. Therefore, it offers valuable points of reference for the implementation of innovative digital health services. Building on insights from this study, actionable metrics can be developed to assess the trustworthiness of digital technologies in health care.


Exploring Psychophysical and Neurophysiological Responses to Intra-Epidermal Electrical Stimuli in Patients With Persistent Spinal Pain Syndrome Type 2 with a Spinal Cord Stimulator.
There is a lack of measures that provide insights into how spinal cord stimulation (SCS) modulates nociceptive function in patients with persistent spinal pain syndrome type 2 (PSPS-T2). Recently, we observed altered nociceptive detection thresholds (NDTs) in response to intra-epidermal electrical stimulation (IES) on the feet of PSPS-T2 patients when dorsal root ganglion stimulation was turned on. Furthermore, we observed altered NDTs and evoked potentials (EPs) in response to IES on the hands of PSPS-T2 patients. To explore whether EPs were obstructed by SCS artifacts, we applied IES twice to the hands of patients with SCS turned on (SCS-ON/ON group). To explore possible confounding effects of SCS outside the stimulated area, we repeated IES on the hands of these patients, once with SCS turned off and subsequently once with SCS turned on (SCS-OFF/ON group). The results demonstrated that EPs were not obstructed by SCS artifacts. Additionally, NDTs and EPs did not significantly change between measurements in the SCS-ON/ON and the SCS-OFF/ON groups. Therefore, the results suggested that possible confounding effects of SCS outside the nociceptive system did not interfere with the detection task performance. This work warrants further exploration of NDT-EP phenomena in response to IES at the painful feet of patients.Clinical Relevance-This work contributes to developing a clinical tool to explore psychophysical and neurophysiological biomarkers for observing modulating effects of SCS in patients with PSPS-T2.


Assessment of the hepatic tumor extracellular matrix using elastin-specific molecular magnetic resonance imaging in an experimental rabbit cancer model.
To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14-28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.


Early change detection in humans as revealed by auditory brainstem and middle-latency evoked potentials.
The ability to detect unexpected novel stimuli is crucial for survival, as it might urge a prompt adaptive response. Human auditory novelty detection has been associated to the mismatch negativity long-latency auditory-evoked potential, peaking at 100-200 ms. Yet, recent animal studies showing novelty responses at a very short latency (about 20-30 ms) in individual neurons already at the level of the midbrain and thalamus suggest that novelty detection might be a basic principle of the functional organization of the auditory system, expanding from lower levels in the brainstem along the auditory pathway up to higher-order areas of the cerebral cortex. To test this suggestion, we here measured auditory brainstem and middle latency response (MLR) to frequency novel stimuli embedded in an oddball sequence. To oversee refractoriness confounds a 'control block' was used. The results showed that occasional changes in auditory frequency information were detected as early as 30 ms (Pa waveform of the MLR) after stimulus onset. The control block precluded these effects as resulting merely from refractoriness, altogether supporting the notion of 'true' early auditory change detection in humans, matching the latency range of auditory novelty responses described in individual neurons of subhuman species. Our results suggest that auditory change detection of frequency information is a multistage process that occurs at the primary auditory cortex and is transmitted to the higher levels of the auditory pathway.