Plasmon-induced electrical conduction in molecular devices.
Metal nanoparticles (NPs) respond to electromagnetic waves by creating surface plasmons (SPs), which are localized, collective oscillations of conduction electrons on the NP surface. When interparticle distances are small, SPs generated in neighboring NPs can couple to one another, creating intense fields. The coupled particles can then act as optical antennae capturing and refocusing light between them. Furthermore, a molecule linking such NPs can be affected by these interactions as well. Here, we show that by using an appropriate, highly conjugated multiporphyrin chromophoric wire to couple gold NP arrays, plasmons can be used to control electrical properties. In particular, we demonstrate that the magnitude of the observed photoconductivity of covalently interconnected plasmon-coupled NPs can be tuned independently of the optical characteristics of the molecule-a result that has significant implications for future nanoscale optoelectronic devices.


Evolution of gamma-butyrolactone synthases and receptors in Streptomyces.
The gamma-butyrolactone regulatory system triggers secondary metabolism and/or morphological development in the Gram-positive, soil-dwelling, filamentous bacterial genus Streptomyces. The representative of the gamma-butyrolactones is A-factor in Streptomyces griseus. AfsA is an enzyme for A-factor biosynthesis and ArpA is the A-factor receptor protein that serves as a transcriptional factor by using A-factor as the ligand. Analysis of evolutional relations between AfsA including its homologues and ArpA including its homologues, all of which are widely distributed in Streptomyces, revealed great differences in the topologies of their phylogenetic trees. Therefore, the combinations of AfsA homologues and ArpA homologues in a given Streptomyces strain appear to have changed during the evolution. Even if an afsA homologue and an arpA homologue locate adjacently on the chromosome, the evolutional history of the individuals was found to be different in some Streptomyces strains. In addition, the phylogenetic analyses suggested that the ancestral ArpA protein had existed and functioned as a DNA-binding protein, not as a gamma-butyrolactone receptor, before the appearance of a gamma-butyrolactone receptor protein in the course of the bacterial evolution. Some Streptomyces strains have plasmids encoding AfsA/ArpA homologues, which suggests that plasmids have played an important role in the distribution of afsA/arpA homologues. During the evolution, once a Streptomyces strain acquired different afsA/arpA homologues, it may have developed a new gamma-butyrolactone regulatory system reconstructing the regulatory systems for secondary metabolism and/or morphogenesis. This idea is consistent with the diverged combination of AfsA homologues and ArpA homologues in a Streptomyces strain.


The Potential for QT Interval Prolongation with Chronic Azithromycin Therapy in Adult Cystic Fibrosis Patients.
Oral azithromycin (AZM) has been shown to reduce airway inflammation and disrupt biofilm formation. However, chronic AZM therapy may result in QT interval (QTc) prolongation. The goals of this study were twofold: (i) to characterize the risk of QTc prolongation in adult patients with cystic fibrosis (CF) receiving AZM and other potential QTc-prolonging agents, and (ii) to describe and capture the number of potential QTc-prolonging agents patients with CF are prescribed. A retrospective study was conducted over a 3-year period in an adult CF center. QTc values were recorded from electrocardiograms. Univariate and multivariate analyses were conducted. Standard QTc prolongation definitions (males ≥ 450 msec, females ≥ 470 msec) were used. A total of 89 adult CF patient's records were reviewed. Sixty-eight patients received chronic AZM therapy. Two male patients had prolonged QTc, but only 1 received chronic AZM therapy. The median QTc interval between patients receiving and not receiving AZM was not significantly different (405 [interquartile range, IQR: 388-425] vs 394 [IQR: 384-413] msec, respectively, p=0.14). Also, the QTc interval for patients taking chronic AZM 500 mg Monday/Wednesday/Friday or 250 mg daily was not significantly different (401 [IQR: 383-419] vs 409 [IQR: 394-427] msec, respectively, p=0.48). When stratified by the number of QTc-prolonging medications (AZM vs no AZM), there was no significant difference in median QTc values between patients receiving zero to ≥ 5 QTc-prolonging medications. An association between chronic AZM therapy and longer QTc intervals or significant QTc prolongation was not shown.


Cultivar and nitrogen splitting effects on Amaranth forage yield and weed community.
A 2 year field study was carried out at Agricultural Faculty of Shahid Chamran University of Ahvaz (Iran), in order to evaluate the response of Amaranth cultivars and weed dynamic to N splitting methods. Three Amaranth cultivars (i.e., Amont, Trigin and Plainsman) were grown in three N splitting methods (i.e., Commonly, Equal and Semi-equal) that being applied at planting, 12th leaf appearance and stem elongation. A split plot design replicated three times was used which Amaranth cultivars and N splitting methods were arranged in main and sub plots, respectively. Results showed that the highest forage yield was obtained for Trigin with Equal N splitting (i.e., 31.2 t ha(-1)) and Plainsman with Semi-equal N distribution (i.e., 3.8 t ha(-1)) the lowest. Also, the maximum and minimum protein content (%) were obtained for Trigin with Equal N splitting (16%) and Amont with commonly N splitting (11.9%), respectively. It was found that just Trigin with Equal N splitting treatment was the best treatment for both forage quality and quantity yield. Moreover, the weed communities and dominant species changed in response to various N splitting methods and Amaranth cultivars traits. Plainsman with Semi-equal N splitting treatment was the unfavorable treatment for both crop yield and weed infestation. Based on these results it is recommend that N splitting method be applied mainly as an Equal form in Trigin amaranth cultivar, to enhance crop forage yield and reduce weed infestation.


Incomplete screening flexible sigmoidoscopy associated with female sex, age, and increased risk of colorectal cancer.
Several previous studies have found that females and older individuals are at greater risk of having incomplete flexible sigmoidoscopy. However, no prior study has reported the subsequent risk of colorectal cancer (CRC) following incomplete sigmoidoscopy. Using data from 55 791 individuals screened as part of the Colon Cancer Prevention (CoCaP) programme of Kaiser Permanente of Northern California, we evaluated the likelihood of having an inadequate (<40 cm) examination by age and sex, and estimated the risk of distal CRC according to depth of sigmoidoscope insertion at the baseline screening examination. Multivariate estimation of risks was performed using Poisson regression. Older individuals were at a much greater risk of having an inadequate examination (relative risk (RR) for age 80+ years compared with 50-59 years 2.6 (95% confidence interval (CI) 2.3-3.0)), as were females (RR 2.3 (95% CI 2.2-2.5)); these associations were attenuated but remained strong if Poisson models were further adjusted for examination limitations (pain, stool, and angulation). There was an approximate threefold increase in the risk of distal CRC if the baseline sigmoidoscopy did not reach a depth of at least 40 cm; a smaller increase in risk was observed for examinations that reached 40-59 cm. Older individuals and women are at an increased risk of having inadequate sigmoidoscopy. Because inadequate sigmoidoscopy results in an increased risk of subsequent CRC, physicians should consider steps to maximise the depth of insertion of the sigmoidoscope or, failing this, should consider an alternative screening test.


Assessing the impact of non-pharmaceutical interventions (NPI) on the dynamics of COVID-19: A mathematical modelling study of the case of Ethiopia.
The World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020 and by November 14, 2020 there were 53.3M confirmed cases and 1.3M reported deaths in the world. In the same period, Ethiopia reported 102K cases and 1.5K deaths. Effective public health preparedness and response to COVID-19 requires timely projections of the time and size of the peak of the outbreak. Currently, Ethiopia under the COVAX facility has begun vaccinating high risk populations but due to vaccine supply shortages and the absence of an effective treatment, the implementation of NPIs (non-pharmaceutical interventions), like hand washing, wearing face coverings or social distancing, still remain the most effective methods of controlling the pandemic as recommended by WHO. This study proposes a modified Susceptible Exposed Infected and Recovered (SEIR) model to predict the number of COVID-19 cases at different stages of the disease under the implementation of NPIs at different adherence levels in both urban and rural settings of Ethiopia. To estimate the number of cases and their peak time, 30 different scenarios were simulated. The results indicated that the peak time of the pandemic is different in urban and rural populations of Ethiopia. In the urban population, under moderate implementation of three NPIs the pandemic will be expected to reach its peak in December, 2020 with 147,972 cases, of which 18,100 are symptomatic and 957 will require admission to an Intensive Care Unit (ICU). Among the implemented NPIs, increasing the coverage of wearing masks by 10% could reduce the number of new cases on average by one-fifth in urban-populations. Varying the coverage of wearing masks in rural populations minimally reduces the number of cases. In conclusion, the models indicate that the projected number of hospital cases during the peak time is higher than the Ethiopian health system capacity. To contain symptomatic and ICU cases within the health system capacity, the government should pay attention to the strict implementation of the existing NPIs or impose additional public health measures.


Oxidized dimeric Scapharca inaequivalvis. Co-driven perturbation of the redox equilibrium.
The dimeric hemoglobin isolated from Scapharca inaequivalvis, HbI, is notable for its highly cooperative oxygen binding and for the unusual proximity of its heme groups. We now report that the oxidized protein, an equilibrium mixture of a dimeric high spin aquomet form and a monomeric low spin hemichrome, binds ferrocyanide tightly which allows for internal electron transfer with the heme iron. Surprisingly, when ferricyanide-oxidized HbI is exposed to CO, its spectrum shifts to that of the ferrous CO derivative. Gasometric removal of CO leads to the oxidized species rather than to ferrous deoxy-HbI. At equilibrium, CO binds with an apparent affinity (p50) of about 10-25 mm of Hg and no cooperativity (20 degrees C, 10-50 mM buffers at pH 6.1). The kinetics of CO binding under pseudo-first order conditions are biphasic (t1/2 of 15-50 s at pH 6.1). The rates depend on protein, but not on CO concentration. The nitrite-oxidized protein is not reduced readily in the presence of CO unless one equivalent of ferrocyanide, but not of ferricyanide, is added. We infer that ferrocyanide, produced in the oxidation reaction, is tightly bound to the protein forming a redox couple with the heme iron. CO shifts the redox equilibrium by acting as a trap for the reduced heme. The equilibrium and kinetic aspects of the process have been accounted for in a reaction scheme where the internal electron transfer reaction is the rate-limiting step.


A structural and functional study of Gln147 deamidation in αA-crystallin, a site of modification in human cataract.
Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering. The effect of Glu147 deamidation on αA-crystallin in vitro chaperone ability was determined for a variety of aggregating proteins. Compared to the wild type protein, Q147E αA-crystallin generally exhibited slightly reduced chaperone ability and a small loss of overall structure in its central α-crystallin domain while also showing significantly enhanced thermal stability and a tendency to form slightly larger oligomers. As αA-crystallin is the major lens protein, even a small loss of function could combine with other sources of age-related damage to the crystallins to contribute to lens opacification.


Lhx1 is required for specification of the renal progenitor cell field.
In the vertebrate embryo, the kidney is derived from the intermediate mesoderm. The LIM-class homeobox transcription factor lhx1 is expressed early in the intermediate mesoderm and is one of the first genes to be expressed in the nephric mesenchyme. In this study, we investigated the role of Lhx1 in specification of the kidney field by either overexpressing or depleting lhx1 in Xenopus embryos or depleting lhx1 in an explant culture system. By overexpressing a constitutively-active form of Lhx1, we established its capacity to expand the kidney field during the specification stage of kidney organogenesis. In addition, the ability of Lhx1 to expand the kidney field diminishes as kidney organogenesis transitions to the morphogenesis stage. In a complimentary set of experiments, we determined that embryos depleted of lhx1, show an almost complete loss of the kidney field. Using an explant culture system to induce kidney tissue, we confirmed that expression of genes from both proximal and distal kidney structures is affected by the absence of lhx1. Taken together our results demonstrate an essential role for Lhx1 in driving specification of the entire kidney field from the intermediate mesoderm.


Junior doctors, burnout and wellbeing: Understanding the experience of burnout in general practice registrars and hospital equivalents.
Australian junior doctors are stressed and report high rates of burnout. The aim of this study was to understand the experience of burnout in general practice registrars and hospital equivalents. Qualitative, semi-structured interviews were completed until saturation and thematically analysed. Stress was common among the interviewees, and the causes of stress were multifactorial. The junior doctors were aware of burnout prevention strategies but were not always effectively undertaking them. They were more likely to be feeling stressed when their expectations regarding workplace support were not met and when they believed they were practising beyond the level of their own abilities. On the basis of our findings, we propose a multifactorial model of junior doctor burnout. This model warrants further investigation to inform policies to reduce burnout in junior doctors and ensure a research-based solution is found to the progressive concerns regarding junior doctor burnout and suicides.


An Integrated District Mapping Strategy for Loiasis to Enable Safe Mass Treatment for Onchocerciasis in Gabon.
The lack of a WHO-recommended strategy for onchocerciasis treatment with ivermectin in hypo-endemic areas co-endemic with loiasis is an impediment to global onchocerciasis elimination. New loiasis diagnostics (LoaScope; Loa antibody rapid test) and risk prediction tools may enable safe mass treatment decisions in co-endemic areas. In 2017-2018, an integrated mapping strategy for onchocerciasis, lymphatic filariasis (LF), and loiasis, aimed at enabling safe ivermectin treatment decisions, was piloted in Gabon. Three ivermectin-naïve departments suspected to be hypo-endemic were selected and up to 100 adults per village across 30 villages in each of the three departments underwent testing for indicators of onchocerciasis, LF, and loiasis. An additional 67 communities in five adjoining departments were tested for loiasis to extend the prevalence and intensity predictions and possibly expand the boundaries of areas deemed safe for ivermectin treatment. Integrated testing in the three departments revealed within-department heterogeneity for all the three diseases, highlighting the value of a mapping approach that relies on cluster-based sampling rather than sentinel sites. These results suggest that safe mass treatment of onchocerciasis may be possible at the subdepartment level, even in departments where loiasis is present. Beyond valuable epidemiologic data, the study generated insight into the performance of various diagnostics and the feasibility of an integrated mapping approach utilizing new diagnostic and modeling tools. Further research should explore how programs can combine these diagnostic and risk prediction tools into a feasible programmatic strategy to enable safe treatment decisions where loiasis and onchocerciasis are co-endemic.


Molecular understanding of peripheral T-cell lymphomas, not otherwise specified (PTCL, NOS): A complex disease category.
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) includes various diseases. Attempts have been made to identify distinct properties of disease within the PTCL, NOS classification and evaluate their significance to prognosis. Comprehensive gene expression analysis and evaluation of genomic abnormalities have successfully identified specific diseases from heterogeneous PTCL, NOS cases. For example, cases with properties of T follicular helper cells have been identified and classified as an entity resembling angioimmunoblastic T-cell lymphoma (AITL), based on both immunohistochemistry and genomic features. Here, we focus on the molecular pathology of PTCL, NOS and discuss recent changes relevant to its classification.


The impact of intravenous fluid administration on complication rates in bowel surgery within an enhanced recovery protocol: a randomized controlled trial.
A randomized controlled trial was conducted to test the hypothesis that there is no difference in complications in patients receiving intravenous (iv) water and electrolyte, based on either stroke volume or clinical indicators at bowel surgery. Eligible patients were randomized either to intra-operative iv administration of fluid boluses based on stroke volume measured by oesophageal Doppler (probe arm) or to iv fluid based on clinical indicators (no-probe arm). The end-point was the complication rate, defined as deviation from an uneventful postoperative course. Surgery was defined as elective bowel resection with primary anastomosis. All patients were on an enhanced recovery protocol. A randomized controlled trial suggested a sample size of 91 patients. Ninety-one patients were randomized. Seventeen were excluded because of withdrawal of consent, failure of the procedure or cancellation of surgery. Patients were comparable for age (P = 0.89), gender (P = 0.14), body mass index (BMI) (P = 0.7), American Society of Anesthesiology (ASA) score (P > 0.9), race (P = 0.55), colorectal POSSUM score (P = 0.11), comorbidity (P = 0.4), previous operations (P = 0.45) and diagnosis (P = 0.50). Physiological and Operative Severity Score for the Enumeration of Morbidity and Mortality (POSSUM)-predicted mortality was higher in the test (probe) arm (P = 0.011). No differences were observed in epidural analgesia (P = 0.16), type of resection (P = 0.43), incision length (P = 0.40), type of incision (P = 0.47), operation time (P = 0.92), estimated blood loss (EBL) (P = 0.56), time to ambulation (P = 0.95), flatus (P = 0.37), diet (P = 0.17), removal of the epidural anaesthesia (P = 0.26) and length of hospital stay (LOS) (P = 0.575). Intra-operative fluids administered were 3.1 (0.7-77) vs 4 (0.9-6.2) liters (P = 0.53). Postoperative fluids administered were 12.5 (5.5-84.6) vs 11.3 (3.4-49.8) (P = 0.42). Overall and septic complication rates were significantly decreased in the test arm (7/32 (22%) vs 19/40 (49%) (P = 0.022) and 2/32 (6.2%) vs 12/40 (30%) (P = 0.05), respectively). Intra-operative administration of iv water and electrolyte during bowel surgery, based on stroke volume measured using oesophageal Doppler, was associated with decreased complication rates.


A survey of the mycobiota associated with larvae of the black soldier fly (Hermetia illucens) reared for feed production.
Feed security, feed quality and issues surrounding the safety of raw materials are always of interest to all livestock farmers, feed manufacturers and competent authorities. These concerns are even more important when alternative feed ingredients, new product developments and innovative feeding trends, like insect-meals, are considered. The black soldier fly (Hermetia illucens) is considered a good candidate to be used as feed ingredient for aquaculture and other farm animals, mainly as an alternative protein source. Data on transfer of contaminants from different substrates to the insects, as well as the possible occurrence of toxin-producing fungi in the gut of non-processed insects are very limited. Accordingly, we investigated the impact of the substrate/diet on the intestinal mycobiota of H. illucens larvae using culture-dependent approaches (microbiological analyses, molecular identification through the typing of isolates and the sequencing of the 26S rRNA D1/D2 domain) and amplicon-based next-generation sequencing (454 pyrosequencing). We fed five groups of H. illucens larvae at the third growing stage on two substrates: chicken feed and/or vegetable waste, provided at different timings. The obtained results indicated that Pichia was the most abundant genus associated with the larvae fed on vegetable waste, whereas Trichosporon, Rhodotorula and Geotrichum were the most abundant genera in the larvae fed on chicken feed only. Differences in the fungal communities were highlighted, suggesting that the type of substrate selects diverse yeast and mold genera, in particular vegetable waste is associated with a greater diversity of fungal species compared to chicken feed only. A further confirmation of the significant influence of diet on the mycobiota is the fact that no operational taxonomic unit common to all groups of larvae was detected. Finally, the killer phenotype of isolated yeasts was tested, showing the inhibitory activity of just one species against sensitive strains, out of the 11 tested species.


Single shot intraoperative excretory urography for the immediate evaluation of renal trauma.
We reviewed the quality and usefulness of single shot intraoperative excretory urography (IVP) for evaluating suspected upper urinary tract trauma at our trauma center. Between 1990 and 1997 single shot intraoperative IVP for staging renal injuries was performed in 50 patients in whom clinical instability and/or major associated injuries mandated an intraoperative study. Contrast material (2 ml/kg) was injected intravenously and images were obtained after 10 minutes. The quality and usefulness of each study were scored by a single attending urologist on a scale of 1-worst to 5-best. Intraoperative study quality was generally good (average score 3.84). The information obtained was generally considered useful for determining urological treatment (average score 3.96). In 16 patients (32%) intraoperative IVP findings safely obviated renal exploration. No contrast medium reactions were noted and no complications developed that were attributable to intraoperative IVP. Intraoperative single shot, high dose IVP is safe, efficient and of high quality in the majority of cases when performed as recommended. This study often provides important information that facilitates rapid and accurate decision-making. Intraoperative IVP is a useful tool for guiding the exploration of penetrating renal injuries and confirming blunt renal injuries that may be safely observed.


Occurrence, Fate, Effects, and Risks of Dexamethasone: Ecological Implications Post-COVID-19.
The recent outbreak of respiratory syndrome-coronavirus-2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has led to the widespread use of therapeutics, including dexamethasone (DEXA). DEXA, a synthetic glucocorticoid, is among the widely administered drugs used to treat hospitalized COVID-19 patients. The global COVID-19 surge in infections, consequent increasing hospitalizations, and other DEXA applications have raised concerns on eminent adverse ecological implications to aquatic ecosystems. Here, we aim to summarize published studies on DEXA occurrence, fate, and effects on organisms in natural and engineered systems as, pre-COVID, the drug has been identified as an emerging environmental contaminant. The results demonstrated a significant reduction of DEXA in wastewater treatment plants, with a small portion, including its transformation products (TPs), being released into downstream waters. Fish and crustaceans are the most susceptible species to DEXA exposure in the parts-per-billion range, suggesting potential deleterious ecological effects. However, there are data deficits on the implications of DEXA to marine and estuarine systems and wildlife. To improve DEXA management, toxicological outcomes of DEXA and formed TPs should entail long-term studies from whole organisms to molecular effects in actual environmental matrices and at realistic exposure concentrations. This can aid in striking a fine balance of saving human lives and protecting ecological integrity.


[Metastasis in the glans of prostatic adenocarcinoma. Apropos of a case].
Case of an 83 year-old male with metastatic penis cancer located at the glans, secondary to moderately differentiated prostatic adenocarcinoma. There was early metastasis clinically expressed as several painful and ulcerous nodes at the glans corona and paraphimosis. The clinical rareness of metastasis in a porous body (glans) as opposed to the more frequent cavernous ones is outlined. Diagnosis was made through biopsy. Treatment is complex since neither radiotherapy, chemotherapy or hormonal-therapy appear to be effective. Occasionally, in the event of solitary nodes partial penectomy should be indicated. Usually, the only feasible treatment is palliative. Presence of such type of metastasis should always be considered as a sign of poor prognosis.


Macrophage-derived chemokine is localized to thymic medullary epithelial cells and is a chemoattractant for CD3(+), CD4(+), CD8(low) thymocytes.
Macrophage-derived chemokine (MDC) is a recently identified CC chemokine that is a potent chemoattractant for dendritic cells, natural killer (NK) cells, and the Th2 subset of peripheral blood T cells. In normal tissues, MDC mRNA is expressed principally in the thymus. Immunohistochemical analysis performed on 5 human postnatal thymuses showed high MDC immunoreactivity, which was selectively localized to epithelial cells within the medulla. To examine the effects of MDC on immature T cells, we have identified cDNA clones for mouse and rat MDC. Expression of MDC in murine tissues is also highly restricted, with significant levels of mRNA found only in the thymus. Thymocytes express high-affinity binding sites for MDC (kd = 0.7 nmol/L), and, in vitro, MDC is a chemoattractant for these cells. MDC-responsive murine thymocytes express mRNA for CCR4, a recently identified receptor for MDC. Phenotypic analysis of MDC-responsive cells shows that they are enriched for a subset of double-positive cells that express high levels of CD3 and CD4 and that have reduced levels of CD8. This subset of MDC-responsive cells is consistent with the observed expression of MDC within the medulla, because more mature cells are found there. MDC may therefore play a role in the migration of T-cell subsets during development within the thymus.


Extracellular matrix metalloproteinases inducer gene polymorphism and reduced serum matrix metalloprotease-2 activity in preeclampsia patients.
Preeclampsia increases the risk of pregnancy-related complications, nevertheless a successful spiral vessel remodeling, and trophoblast invasion reduces disorders of pregnancy. Matrix metalloproteinase-2 (MMP-2) clears the path for trophoblast invasion, and activation of MMP-2 largely depends on extracellular matrix metalloproteinases inducer (EMMPRIN) protein. This study aimed to investigate EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia patients. Archival whole blood and serum samples of 74 preeclampsia and 66 normotensive pregnant women age-matched were used in this case-control study. Genomic DNA was extracted from the whole blood samples and EMMPRIN gene amplified with specific primers following fragments sequence mutation analysis. Serum MMP-2 activity was determined using enzyme-linked immunosorbent assay (ELISA) and socio-demographic data of participants retrieved from the database. Age of preeclampsia patients (32.78 ± 6.39) years and body mass index (BMI) (33.09 ± 7.27) kg/m2 compared with the normotensive counterparts (32.33 ± 5.56) years and (32.33 ± 5.56) kg/m2,respectively, were not statistically significant (P > 0.05). Serum matrix metalloprotease-2 (MMP-2) activity was significantly reduced in preeclampsia group (16.34 ± 7.07) compared with the normotensives (25.63 ± 4.56) (P < 0.001), and rs424243T/G variant (55.6%) was overrepresented among the cases compared with the normotensives (16.7%). The single-nucleotide polymorphism T/G was found to be associated with preeclampsia (odds ratio [OR] = 7.63; 95% confidence interval [CI] = 3.95-14.75; P < 0.0001). Decreased activity of MMP-2 and rs424243T/G SNP of EMMPRIN gene was reported in preeclampsia. These preliminary data warrant a further investigation into the relationship between EMMPRIN gene polymorphism and MMP-2 activity in preeclampsia.


Nutrition-sensitive lockdowns: conceptual framework and empirical insights from Africa during COVID-19.
Countries facing challenges of nutrition security confront a trade-off when dealing with pandemics such as COVID-19. Implementing lockdown measures, widely used worldwide, can help "flatten the curve" (of disease), but such measures may worsen nutrition security. We aim to identify and justify nutrition-sensitive lockdown measures to reduce trade-offs with nutrition security. We propose a conceptual framework which distinguishes eight lockdown measures and six pathways to nutrition security. To demonstrate the relevance of the pathways, we reviewed emerging literature on COVID-19 and nutrition security. We analysed the content of 1,188 newspaper articles on lockdown effects in five African countries - Benin, Ghana, Kenya, Uganda and Zambia. Some lockdown measures, such as closing workplaces and restricting movement, potentially worsen nutrition far more than others - banning events and public gatherings have far lesser impacts on nutrition. This can be seen from the framework, literature, and is supported by the analysis of newspaper reports in the five countries. It is better when possible to test and trace disease than to lockdown. But when lockdowns are needed, then first recourse should be to measures that have few nutritional consequences, such as banning public events. When more drastic measures are necessary, look to mitigate nutritional harm by, for example, exempting farm labour from restrictions on movement, by replacing school meals with take-home rations, and, above all, providing income support to households most affected and most vulnerable.


BAFF selectively enhances the survival of plasmablasts generated from human memory B cells.
The generation of Ig-secreting cells (ISCs) from memory B cells requires interactions between antigen-specific (Ag-specific) B cells, T cells, and dendritic cells. This process must be strictly regulated to ensure sufficient humoral immunity while avoiding production of pathogenic autoantibodies. BAFF, a member of the TNF family, is a key regulator of B cell homeostasis. BAFF exerts its effect by binding to three receptors - transmembrane activator of and CAML interactor (TACI), B cell maturation antigen (BCMA), and BAFF receptor (BAFF-R). To elucidate the contribution of BAFF to the differentiation of B cells into ISCs, we tracked the fate of human memory B cells stimulated with BAFF or CD40L. BAFF and CD40L significantly increased the overall number of surviving B cells. This was achieved via distinct mechanisms. CD40L induced proliferation of nondifferentiated blasts, while BAFF prevented apoptosis of ISCs without enhancing proliferation. The altered responsiveness of activated memory B cells to CD40L and BAFF correlated with changes in surface phenotype such that expression of CD40 and BAFF-R were reduced on ISCs while BCMA was induced. These results suggest BAFF may enhance humoral immunity in vivo by promoting survival of ISCs via a BCMA-dependent mechanism. These findings have wide-ranging implications for the treatment of human immunodeficiencies as well as autoimmune diseases.


Integration of active and passive polymer optics.
We demonstrate a wafer scale fabrication process for integration of active and passive polymer optics: Polymer DFB lasers and waveguides. Polymer dye DFB lasers are fabricated by combined nanoimprint and photolithography (CNP). The CNP fabrication relies on an UV transparent stamp with nm sized protrusions and an integrated metal shadow mask. In the CNP process, a combined UV mask and nanoimprint stamp is embossed into the resist, which is softened by heating, and UV exposed. Hereby the mm to microm sized features are defined by the UV exposure through the metal mask, while nm-scale features are formed by mechanical deformation (nanoimprinting). The lasers are integrated with undoped SU-8 polymer waveguides. The waferscale fabrication process has a yield above 90% and the emission wavelengths are reproduced within 2 nm. Confinement of the light on the chip is demonstrated, and the influence on the laser wavelength from temperature and refractive index changes in the surroundings is investigated, pointing towards the use of the described fabrication method for on-chip polymer sensor systems.


Influence of 90-day simulated microgravity on human tendon mechanical properties and the effect of resistive countermeasures.
While microgravity exposure is known to cause deterioration of skeletal muscle performance, little is known regarding its effect on tendon structure and function. Hence, the aims of this study were to investigate the effects of simulated microgravity on the mechanical properties of human tendon and to assess the effectiveness of resistive countermeasures in preventing any detrimental effects. Eighteen men (aged 25-45 yr) underwent 90 days of bed rest: nine performed resistive exercise during this period (BREx group), and nine underwent bed rest only (BR group). Calf-raise and leg-press exercises were performed every third day using a gravity-independent flywheel device. Isometric plantar flexion contractions were performed by using a custom-built dynamometer, and ultrasound imaging was used to determine the tensile deformation of the gastrocnemius tendon during contraction. In the BR group, tendon stiffness estimated from the gradient of the tendon force-deformation relation decreased by 58% (preintervention: 124 +/- 67 N/mm; postintervention: 52 +/- 28 N/mm; P < 0.01), and the tendon Young's modulus decreased by 57% postintervention (P < 0.01). In the BREx group, tendon stiffness decreased by 37% (preintervention: 136 +/- 66 N/mm; postintervention: 86 +/- 47 N/mm; P < 0.01), and the tendon Young's modulus decreased by 38% postintervention (P < 0.01). The relative decline in tendon stiffness and Young's modulus was significantly (P < 0.01) greater in the BR group compared with the BREx group. Unloading decreased gastrocnemius tendon stiffness due to a change in tendon material properties, and, although the exercise countermeasures did attenuate these effects, they did not completely prevent them. It is suggested that the total loading volume was not sufficient to completely prevent alterations in tendon mechanical properties.


Sensitivity to reward is associated with snack and sugar-sweetened beverage consumption in adolescents.
High intake of palatable foods, such as energy-dense snacks and sugar-sweetened beverages (SSBs), is common among adolescents. An individual's sensitivity to reward (SR) may influence these intakes. The main objective of this study was to investigate the association between SR and both snack and SSB intake among adolescents. A representative cross-sectional survey was conducted among 1104 14- to 16-year-olds (mean age = 14.7 ± 0.8 years; 50.9 % boys; 18.0 % overweight) in Flanders. Daily intakes were measured by a food frequency questionnaire. SR was assessed using the behavioral activation system (BAS) scales. Multilevel regression analyses (two level: adolescent school) were conducted using STATA version 13. BAS drive was positively associated with daily intakes of SSBs (13.79 %, p < 0.01), unhealthy snacks (5.42 %, p < 0.001), and energy and nutrients derived from SSBs (p < 0.001) and snacks (p < 0.01). BAS reward responsiveness (RR) was only positively associated with intake of unhealthy snacks (3.85 %, p < 0.05), healthy snacks (6.41 %, p < 0.05), and fat (4.05 %, p < 0.01) and Na (3.89 %, p < 0.05) from snacks. Interaction effects of gender and BAS RR (p < 0.05) were found. Significant positive associations between BAS RR and daily intakes of energy from snacks (6.48 %, p < 0.01) and fat from snacks (7.22 %, p < 0.001) were found only for girls. SR was associated with snack and SSB consumption in adolescents, especially in girls. These findings suggest that SR should be taken into account when designing interventions to improve the snack and SSB intake of adolescents.


New riches in carbaporphyrin chemistry: silver and gold organometallic complexes of benzocarbaporphyrins.
The NH-N-NH-N core of the porphyrin system represents one of the best studied and most versatile platforms for coordination chemistry. However, the replacement of one or more of the interior nitrogens with carbon atoms would be expected to diminish the ability of these systems to form metallo derivatives considerably. Despite this expectation, carbaporphyrinoid systems have been shown to form stable organometallic derivatives. Although azuliporphyrins and benziporphyrins act as dianionic ligands, benzocarbaporphyrins are trianionic ligands. Treatment of five different meso unsubstituted benzocarbaporphyrins and two different meso tetraarylbenzocarbaporphyrins with excess silver(I) acetate afforded 65-97% yields of the corresponding silver(III) organometallic derivatives. The insertion of silver metal was confirmed by mass spectrometry and X-ray crystallography. The UV-vis spectra showed a strong Soret band at wavelengths between 437 and 451 nm, together with a series of Q-type bands at longer wavelengths. The new metallo carbaporphyrins demonstrate the presence of a strong diatropic ring current in their proton NMR spectra, and carbon-13 NMR spectroscopy indicates that the derivatives retain a plane of symmetry. The reaction of meso tetraaryl carbaporphyrins with gold(III) acetate afforded the related gold(III) complexes, and these also showed strongly porphyrin-like aromatic characteristics. The UV-vis spectra for the gold complexes again showed a strong Soret band between 437-439 nm, but a secondary band near 400 nm is somewhat intensified for the gold species compared to the spectra for the related silver(III) meso tetrasubstituted carbaporphyrins. The ring currents observed for the gold(III) complexes by proton NMR spectroscopy were comparable to those of the silver(III) derivatives, implying that both series have similar macrocyclic conformations. Cyclic voltammetry was performed on two different carbaporphyrins, their silver(III) derivatives, and a gold(III) complex. The silver complexes display a reversible cathodic wave that is assigned to the Ag(III/II) couple. However, the gold porphyrinoid gave a value for the reductive wave that could be due to a gold(III/II) couple or a ligand-based process.


Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle.
Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species (ROS). Recent evidence suggests that radicals and other ROS are an underlying aetiology in exercise-induced disturbances in muscle redox status. These exercise-induced redox disturbances in skeletal muscle are postulated to contribute to both muscle fatigue and/or exercise-induced muscle injury. To defend against ROS, muscle cells contain complex cellular defence mechanisms to reduce the risk of oxidative injury. Two major classes (enzymic and non-enzymic) of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell. Primary antioxidant enzymes include superoxide dismutase (EC 126.96.36.199; SOD), GSH peroxidase (EC 22.214.171.124; GPX), and catalase (EC 220.127.116.11); these enzymes are responsible for removing superoxide radicals, H2O2 and organic hydroperoxides, and H2O2 respectively. Important non-enzymic antioxidants include vitamins E and C, beta-carotene, GSH and ubiquinones. Vitamin E, beta-carotene and ubiquinone are located in lipid regions of the cell, whereas GSH and vitamin C are in aqueous compartments of the cell. Regular endurance training promotes an increase in both total SOD and GPX activity in actively-recruited skeletal muscles. High-intensity exercise training has been shown to be generally superior to low-intensity exercise in the upregulation of muscle SOD and GPX activities. Also, training-induced upregulation of antioxidant enzymes is limited to highly-oxidative skeletal muscles. The effects of endurance training on non-enzymic antioxidants remain a relatively uninvestigated area.


Vasodilator therapy in acute myocardial infarction. A comparison of sodium nitroprusside and nitroglycerin.
Twenty-six patients with complicated acute myocardial infarction were studied in order to compare the hemodynamic effects of sodium nitroprusside (NP) and nitroglycerin (GTN). All patients received NP and 18 of the 26 also received GTN to evaluate both drugs in the same individuals. Both agents produced significant declines in mean arterial pressure, total peripheral resistance (TPR), and heart rate systolic blood pressure product. However, in the 18 patients who received both drugs GTN produced a greater fall (P less than 0.05) in pulmonary capillary wedge pressure (PCW) (25 to 15 mm Hg) than did NP (24 to 17 mm Hg) and a greater increment (P less than 0.01) in (see article) (0.98 to 1.43) than NP (0.98 to 1.16). These data confirm the potent vasodilatory effects of NP and GTN and suggest that NP has a relatively balanced effect on the arterial and venous circulation, and GTN seems to produce more potent venodilatation than arterial dilatation. These observations provide a basis for a more rational choice of vasodilator agents based on initial hemodynamic measurements in complicated acute myocardial infarction.


Vestibular-ocular accommodation reflex in man.
Stimulation of the vestibular system by angular acceleration produces widespread sensory and motor effects. The present study was designed to study a motor effect which has not been reported in the literature, i.e., the influence of rotary acceleration of the body on ocular accommodation. The accommodation of 10 young men was recorded before and after a high-level deceleration to zero velocity following 30 s of rotation. Accommodation was recorded continuously on an infrared optometer for 110 s under two conditions; while the subjects observed a target set at the far point, and while they viewed the same target through a 0.3-mm pinhole. Stimulation by high-level rotary deceleration produced positive accommodation or a pseudomyopia under both conditions, but the positive accommodation was substantially greater and lasted much longer during fixation through the pinhole. It is hypothesized that this increase in accommodation is a result of a vestibular-ocular accommodation reflex.


The role of T and B antigen-binding cells in the immune response to sheep erythrocytes in the lizard, Calotes versicolor.
Our previous studies in the lizard, Calotes versicolor showed that low doses of sheep erythrocytes (SRBC) induced bimodal rosette-forming cell (RFC) response, the first RFC peak appearing on the 2nd day and the second on the 10th day after immunization. In the present study, the type of lymphocytes involved in rosette formation has been analysed with reference to their role in the immune response to sheep erythrocytes. One month after adult thymectomy the formation of the early but not the late rosettes was suppressed. The early RFC were sensitive to the in vitro blocking and cytotoxic activity of rabbit anti-lizard thymocyte globulin (ATG), but not the late rosettes. The interrelationship between these two populations has been studied using cyclophosphamide (Cy) and anti-SRBC antiserum. The development of the early RFC was suppressed when Cy was injected with antigen. However, late RFC (B-RFC) were not detected when the drug treatment was postponed to the 7th day of immunization. The absence of any one RFC peak resulted in the inhibition of plaque-forming cell (PFC) response. Thus, the development of early RFC and late RFC occurs independently, although both are required for effective antibody production. The anti-SRBC antiserum inhibited the formation of RFC and PFC responses, when injected along with low doses of SRBC. When antiserum was given 3 days after immunization, both RFC responses occurred to the normal level, even though PFC response was suppressed, however, when the treatment was delayed up to 6 days normal PFC response occurred. Thus, the presence of antigen in the system for up to 6 days is needed for antibody response. The results indicate the sequential appearance to T and B antigen-binding cells in the spleen of the lizard and their interrelationship in antibody production to sheep erythrocytes.


Diagnosis of small intestinal bacterial overgrowth in the clinical practice.
Gut microbiota plays several beneficial effects on the human host. Its qualitative and/or quantitative unbalance may facilitate the occurrence of small intestinal bacterial overgrowth (SIBO). To review the available data in order to propose a practical approach to SIBO diagnosis in the clinical setting. Full papers from 1990 to present available on the Pubmed database concerning the topic of SIBO diagnosis were critically reviewed. SIBO is common in the presence of one or more predisposing conditions. The clinical picture of SIBO patients is extremely variable, depending of underlying disorders, and both patients and microbiota characteristics. SIBO could be asymptomatic, or leading to aspecific gastrointestinal IBS-like symptoms. In worst cases it may configure a real malabsorption syndrome. Culture of intestinal aspirates remains at present the gold standard for SIBO diagnosis. However a lot of limitations including high costs and invasivity prevent from using this test in the clinical practice. Hydrogen lactulose and especially glucose breath tests are at present the most utilized to reach SIBO diagnosis in the clinical setting, due to their low costs, non invasivity, sufficient accuracy and reproducibility. SIBO should be suspected in the presence of IBS-like symptoms and/or malabsorption syndrome occurring in the presence of disorders predisposing to SIBO development. The most common diagnostic tool is represented at present by hydrogen breath tests.


Accuracy of high b-value diffusion-weighted MRI for prostate cancer detection: a meta-analysis.
Background The diagnostic accuracy of diffusion-weighted imaging (DWI) to detect prostate cancer is well-established. DWI provides visual as well as quantitative means of detecting tumor, the apparent diffusion coefficient (ADC). Recently higher b-values have been used to improve DWI's diagnostic performance. Purpose To determine the diagnostic performance of high b-value DWI at detecting prostate cancer and whether quantifying ADC improves accuracy. Material and Methods A comprehensive literature search of published and unpublished databases was performed. Eligible studies had histopathologically proven prostate cancer, DWI sequences using b-values ≥ 1000 s/mm2, less than ten patients, and data for creating a 2 × 2 table. Study quality was assessed with QUADAS-2 (Quality Assessment of diagnostic Accuracy Studies). Sensitivity and specificity were calculated and tests for statistical heterogeneity and threshold effect performed. Results were plotted on a summary receiver operating characteristic curve (sROC) and the area under the curve (AUC) determined the diagnostic performance of high b-value DWI. Results Ten studies met eligibility criteria with 13 subsets of data available for analysis, including 522 patients. Pooled sensitivity and specificity were 0.59 (95% confidence interval [CI], 0.57-0.61) and 0.92 (95% CI, 0.91-0.92), respectively, and the sROC AUC was 0.92. Subgroup analysis showed a statistically significant ( P = 0.03) improvement in accuracy when using tumor visual assessment rather than ADC. Conclusion High b-value DWI gives good diagnostic performance for prostate cancer detection and visual assessment of tumor diffusion is significantly more accurate than ROI measurements of ADC.


Performance-based clinical tests of balance and muscle strength used in young seniors: a systematic literature review.
Many balance and strength tests exist that have been designed for older seniors, often aged ≥70 years. To guide strategies for preventing functional decline, valid and reliable tests are needed to detect early signs of functional decline in young seniors. Currently, little is known about which tests are being used in young seniors and their methodological quality. This two-step review aims to 1) identify commonly used tests of balance and strength, and 2) evaluate their measurement properties in young seniors. First, a systematic literature search was conducted in MEDLINE to identify primary studies that employed performance-based tests of balance and muscle strength, and which aspects of balance and strength these tests assess in young seniors aged 60-70. Subsequently, for tests used in ≥3 studies, a second search was performed to identify method studies evaluating their measurement properties. The quality of included method studies was evaluated using the Consensus-based Standards for selection of health Measurement Instruments (COSMIN) checklist. Of 3454 articles identified, 295 met the inclusion criteria. For the first objective, 69 balance and 51 muscle strength tests were identified, with variations in administration mode and outcome reporting. Twenty-six balance tests and 15 muscle strength tests were used in ≥3 studies, with proactive balance tests and functional muscle power tests used most often. For the second objective, the search revealed 1880 method studies, of which nine studies (using 5 balance tests and 1 strength test) were included for quality assessment. The Timed Up and Go test was evaluated the most (4 studies), while the Community Balance and Mobility (CBM) scale was the second most assessed test (3 studies). For strength, one study assessed the reliability of the Five times sit-to-stand. Commonly used balance and muscle strength tests in young seniors vary greatly with regards to administration mode and outcome reporting. Few studies have evaluated measurement properties of these tests when used in young seniors. There is a need for standardisation of existing tests to improve their informative value and comparability. For measuring balance, the CBM is a new and promising tool to detect even small balance deficits in balance in young seniors.


The many faces of hypertrophic cardiomyopathy: from developmental biology to clinical practice.
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterized by complex pathophysiology, heterogeneous morphology, and variable clinical manifestations over time. Besides cardiac hypertrophy, the HCM phenotype is characterized by a host of manifestations, including mitral valve and subvalvar abnormalities, subaortic and mid-ventricular left ventricular (LV) obstruction, microvascular dysfunction, myocardial fibrosis, disarray, atrial remodeling, myocardial bridging of epicardial coronary arteries, LV apical aneurysms, and autonomic nervous system abnormalities. Such heterogeneous phenotype still lacks a comprehensive explanation, which cannot be accounted solely by genetic heterogeneity, despite the large number of genes and mutations involved. It is likely that pre-natal and acquired features deriving from the primary genetic defect interact with the environment to produce the final result evident in each patient. Based on novel insights provided by cardiac developmental biology, a common lineage ancestry of several HCM manifestations might be traced back to the pluripotent epicardium-derived cells, which early during heart development differentiate into interstitial fibroblasts, coronary smooth muscle cells, and atrio-ventricular endocardial cushions as mesenchymal cells. To date, the different faces of HCM have not been sufficiently liked or explained. We here attempt to address these issues by describing the various components of the disease, their origin, interaction, and clinical significance.


The Influence of Modified Experimental Dental Resin Composites on the Initial In Situ Biofilm-A Triple-Blinded, Randomized, Controlled Split-Mouth Trial.
The purpose of the study was to investigate the bacterial viability of the initial biofilm on the surface of experimental modified dental resin composites. Twenty-five healthy individuals with good oral hygiene were included in this study. In a split-mouth design, they received acrylic splints with five experimental composite resin specimens. Four of them were modified with either a novel polymeric hollow-bead delivery system or methacrylated polymerizable Irgasan (Antibacterial B), while one specimen served as an unmodified control (ST). A delivery system based on Poly-Pore® was loaded with one of the active agents: Tego® Protect 5000 (Antiadhesive A), Dimethicone (Antiadhesive B), or Irgasan (Antibacterial A). All study subjects refrained from toothbrushing during the study period. Specimens were detached from the splints after 8 h and given a live/dead staining before fluorescence microscopy. A Friedman test and a post hoc Nemenyi test were applied with a significance level at p < 0.05. In summary, all materials but Antibacterial B showed a significant antibacterial effect compared to ST. The results suggested the role of the materials' chemistry in the dominance of cell adhesion. In conclusion, dental resin composites with Poly-Pore-loaded active agents showed antibacterial effectiveness in situ.


The complex genetics of hypoplastic left heart syndrome.
Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS. Mutations in Sap130 and Pcdha9, genes not previously associated with CHD, were validated by CRISPR-Cas9 genome editing in mice as being digenic causes of HLHS. We also identified one subject with HLHS with SAP130 and PCDHA13 mutations. Mouse and zebrafish modeling showed that Sap130 mediates left ventricular hypoplasia, whereas Pcdha9 increases penetrance of aortic valve abnormalities, both signature HLHS defects. These findings show that HLHS can arise genetically in a combinatorial fashion, thus providing a new paradigm for the complex genetics of CHD.


Escherichia coli β-clamp slows down DNA polymerase I dependent nick translation while accelerating ligation.
The nick translation property of DNA polymerase I (Pol I) ensures the maturation of Okazaki fragments by removing primer RNAs and facilitating ligation. However, prolonged nick translation traversing downstream DNA is an energy wasting futile process, as Pol I simultaneously polymerizes and depolymerizes at the nick sites utilizing energy-rich dNTPs. Using an in vitro assay system, we demonstrate that the β-clamp of the Escherichia coli replisome strongly inhibits nick translation on the DNA substrate. To do so, β-clamp inhibits the strand displacement activity of Pol I by interfering with the interaction between the finger subdomain of Pol I and the downstream primer-template junction. Conversely, β-clamp stimulates the 5' exonuclease property of Pol I to cleave single nucleotides or shorter oligonucleotide flaps. This single nucleotide flap removal at high frequency increases the probability of ligation between the upstream and downstream DNA strands at an early phase, terminating nick translation. Besides β-clamp-mediated ligation helps DNA ligase to seal the nick promptly during the maturation of Okazaki fragments.


Warning times for species extinctions due to climate change.
Climate change is likely to become an increasingly major obstacle to slowing the rate of species extinctions. Several new assessment approaches have been proposed for identifying climate-vulnerable species, based on the assumption that established systems such as the IUCN Red List need revising or replacing because they were not developed to explicitly consider climate change. However, no assessment approach has been tested to determine its ability to provide advanced warning time for conservation action for species that might go extinct due to climate change. To test the performance of the Red List system in this capacity, we used linked niche-demographic models with habitat dynamics driven by a 'business-as-usual' climate change scenario. We generated replicate 100-year trajectories for range-restricted reptiles and amphibians endemic to the United States. For each replicate, we categorized the simulated species according to IUCN Red List criteria at annual, 5-year, and 10-year intervals (the latter representing current practice). For replicates that went extinct, we calculated warning time as the number of years the simulated species was continuously listed in a threatened category prior to extinction. To simulate data limitations, we repeated the analysis using a single criterion at a time (disregarding other listing criteria). Results show that when all criteria can be used, the Red List system would provide several decades of warning time (median = 62 years; >20 years for 99% of replicates), but suggest that conservation actions should begin as soon as a species is listed as Vulnerable, because 50% of replicates went extinct within 20 years of becoming uplisted to Critically Endangered. When only one criterion was used, warning times were substantially shorter, but more frequent assessments increased the warning time by about a decade. Overall, we found that the Red List criteria reliably provide a sensitive and precautionary way to assess extinction risk under climate change.


Hepatic collagenolytic activity in rats after carbon tetrachloride poisoning.
1. Collagenolytic activity towards acid-soluble collagen labelled with [(14)C]-proline was assayed in rat liver with and without carbon tetrachloride poisoning. The products of enzymic digestion were found to be free amino acids and peptides. 2. The hepatic collagenolytic activity increased under conditions of single-dose and subacute carbon tetrachloride poisoning, and correlated with hydroxyproline content. The highest activity was found during recovery from subacute poisoning. 3. Under the same experimental conditions, hepatic acid-proteinase activity changed independently of the collagenolytic activity and also of hepatic hydroxyproline content. 4. The increased collagenolytic activity during carbon tetrachloride poisoning was found mainly in the supernatant fraction. 5. The ratio of the collagenolytic activity to hepatic hydroxyproline content increased during recovery from single-dose and subacute poisoning, and decreased during subacute poisoning.


Evaluation of Chemically-Cleavable Linkers for Quantitative Mapping of Small Molecule-Cysteinome Reactivity.
Numerous reagents have been developed to enable chemical proteomic analysis of small molecule-protein interactomes. However, the performance of these reagents has not been systematically evaluated and compared. Herein, we report our efforts to conduct a parallel assessment of two widely used chemically cleavable linkers equipped with dialkoxydiphenylsilane (DADPS linker) and azobenzene (AZO linker) moieties. Profiling a cellular cysteinome using the iodoacetamide alkyne probe demonstrated a significant discrepancy between the experimental results obtained through the application of each of the reagents. To better understand the source of observed discrepancy, we evaluated the key sample preparation steps. We also performed a mass tolerant database search strategy using MSFragger software. This resulted in identifying a previously unreported artifactual modification on the residual mass of the azobenzene linker. Furthermore, we conducted a comparative analysis of enrichment modes using both cleavable linkers. This effort determined that enrichment of proteolytic digests yielded a far greater number of identified cysteine residues than the enrichment conducted prior to protein digest. Inspired by recent studies where multiplexed quantitative labeling strategies were applied to cleavable biotin linkers, we combined this further optimized protocol using the DADPS cleavable linker with tandem mass tag (TMT) labeling to profile the FDA-approved covalent EGFR kinase inhibitor dacomitinib against the cysteinome of an epidermoid cancer cell line. Our analysis resulted in the detection and quantification of over 10,000 unique cysteine residues, a nearly 3-fold increase over previous studies that used cleavable biotin linkers for enrichment. Critically, cysteine residues corresponding to proteins directly as well as indirectly modulated by dacomitinib treatment were identified. Overall, our study suggests that the dialkoxydiphenylsilane linker could be broadly applied wherever chemically cleavable linkers are required for chemical proteomic characterization of cellular proteomes.


Relationship Between Coping Strategies, Religious Attitude, and Optimism of Mothers of Children With Cancer.
The purpose of this study was to examine the relationship between coping strategies, religious attitude, and optimism of mothers of children with cancer. The sample was 97 mothers of children with cancer. To collect data, the Coping Strategy Questionnaire, Religious Attitude Scale, and Life Orientation were used. There were positive correlations between the total score of Coping Strategy Questionnaire and emotional scores of Religious Attitude Scale ( r = 0.170, p = .04). The correlation relationship between mothers' coping, religious tendencies, and optimism tendencies was not significant ( p > .05). There were also positive correlations between Coping Strategy Questionnaire Social Support Seeking subscale and the total scores of Religious Attitude Scale ( r = 0.189, p = .03) and Life Orientation Test ( r = 0.183, p = .03). Mothers with a higher religious attitude had bettter social support and were more optimistic. These results will contribute to understanding the influence of religion in different cultures.


The significance of the micropores at the stem-cement interface in total hip replacement.
Cemented total hip replacement has been performed worldwide to treat patients with osteoarthritis and osteonecrosis, with aseptic loosening as its primary reason for revision. It has been indicated that the stem-cement interfacial porosity may contribute to the early loosening of cemented hip prosthesis. In addition, it is generally accepted that the micropores in bone cement surface and in the bulk material are detrimental to the mechanical integrity of bone cement and act as stress concentrators, resulting in generation of fatigue cracks in the cement mantle. Furthermore, it was demonstrated that the micropores also play an important part in initiation and propagation of fretting wear on polished femoral stems. Taking this into consideration, a detailed review of the potential significance of the micropores in bone cement and the methods that could be employed to reduce porosity is given in this article. It was considered that modern cementing techniques are clinically beneficial and should be applied in surgery to further improve the survivorship of cemented total hip replacement.


Highly enantioselective cross-aldol reactions of acetaldehyde mediated by a dual catalytic system operating under site isolation.
Polystyrene-supported (PS) diarylprolinol catalysts 1 a (Ar = phenyl) and 1 b (Ar = 3,5-bis(trifluoromethyl)phenyl) have been developed. Operating under site-isolation conditions, PS-1 a/1 b worked compatibly with PS-bound sulfonic acid catalyst 2 to promote deoligomerization of paraldehyde and subsequent cross-aldol reactions of the resulting acetaldehyde in one pot, affording aldol products in high yields with excellent enantioselectivities. The effect of water on the performance of the catalytic system has been studied and its optimal amount (0.5 equiv) has been determined. The dual catalytic system (1/2) allows repeated recycling and reuse (10 cycles). The potential of this methodology is demonstrated by a two-step synthesis of a phenoperidine analogue (68% overall yield; 98% ee) and by the preparation of highly enantioenriched 1,3-diols 4 and 3-methylamino-1-arylpropanols 5, key intermediates in the synthesis of a variety of druglike structures.


Pain among the elderly: an action plan.
Pain is the most frequently communicated nursing-sensitive patient outcome among the elderly. An effective action plan to decrease pain among the elderly should encompass both medically based interventions and psychosocial techniques. Nurses who are familiar with the latest information about pain and who are cognizant of and comfortable with their own views about pain are likely to bring about a positive patient outcome. Further research will add to the current knowledge base while laying the groundwork for new interventions.


Probing the Salt Concentration Dependent Nucelobase Distribution in a Single-Stranded DNA-Single-Walled Carbon Nanotube Hybrid with Molecular Dynamics.
The hybrids of single-walled carbon nanotube (SWCNT) and single stranded DNA (ssDNA) are novel nanoscale materials having remarkable applications in nanotechnology. The absorption of nucleobases on the surface of a SWCNT depends strongly on the ionic strength of the medium. In this paper, using atomistic molecular dynamics we have shown that at low salt concentration ssDNA wraps on the surface of SWCNT through hydrophobic π-π stacking between the DNA bases and the sp(2)-hybridized carbon atoms of the carbon nanotube. At high salt concentration, however, the DNA molecule adopts a partially folded structure and the ssDNA-SWCNT wrapping gets weakened significantly due to the self-stacking of the DNA bases. Our study can find relevance in CNT mediated gene delivery processes where subsequent unwrapping of the gene from its carrier is anticipated across the cell membrane regulated by an existing salt concentration gradient.


Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro.
One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.


Immunohistochemical detection of COX-2 in feline and canine actinic keratoses and cutaneous squamous cell carcinoma.
Cyclooxygenase-2 (COX-2) overexpression and its causal role in epidermal carcinogenesis have been demonstrated in human actinic keratoses (AK) and cutaneous squamous cell carcinoma (SCC). The aim of this study was to determine immunohistochemically the level of expression of COX-2 in feline and canine AK (n=18), SCC (n=36) and inflammatory dermatoses (n=24). COX-2 immunoreactivity was detected in all feline and canine SCC. In all specimens, labelled basal and suprabasal neoplastic keratinocytes were localized within and below areas of superficial erosion or ulceration and only scattered deeper tumour cells were positively labelled. In most cases, positive immunoreactivity of keratinocytes was associated with the presence of granulocytes. COX-2 expression was detected in 3/9 canine and 4/9 feline cases of AK and in only one case was associated with inflammation. Inflammatory dermatoses were characterized by positively labelled epidermal and follicular basal and suprabasal keratinocytes that were always associated with granulocyte exocytosis. These results indicate that further study of the effect of using COX-2 inhibitors in the management and prevention of feline and canine cutaneous SCC is warranted. The association between inflammatory cells and COX-2 expressing epidermal cells opens a new line of research regarding the role of COX-2 in SCC oncogenesis. Moreover, further studies should investigate the role of COX-2 in the pathogenesis and management of AK in animals.


How to be at the right place at the right time: the importance of spindle positioning in embryos.
Spindle positioning is an imperative cellular process that regulates a number of different developmental events throughout embryogenesis. The spindle must be properly positioned in embryos not only for the segregation of chromosomes, but also to segregate developmental determinants into different daughter blastomeres. In this review, the role of spindle positioning is explored in several different developmental model systems, which have revealed the diversity of factors that regulate spindle positioning. The C. elegans embryo, the Drosophila neuroblast, and ascidian embryos have all been utilized for the study of polarity-dependent spindle positioning, and exploration of the proteins that are required for asymmetric cell division. Work in the sea urchin embryo has examined the influence of cell shape and factors that affect secondary furrow formation. The issue of size scaling in extremely large cells, as well as the requirement for spindle positioning in developmental fate decisions in vertebrates, has been addressed by work in the Xenopus embryo. Further work in mouse oocytes has examined the roles of actin and myosin in spindle positioning. The data generated from these model organisms have made unique contributions to our knowledge of spindle positioning. Future work will address how all of these different factors work together to regulate the position of the spindle.


Correlation between late gadolinium enhancement and diastolic function in hypertrophic cardiomyopathy assessed by magnetic resonance imaging.
Diastolic dysfunction is common in patients with overt hypertrophic cardiomyopathy (HCM). Steady-state cine magnetic resonance imaging (MRI) enables measurement of the diastolic function of the left ventricle (LV), and late gadolinium enhanced MRI can delineate the presence and extent of fibrosis in HCM. The purpose of this study was to determine the relationship between the extent of myocardial fibrosis demonstrated by late gadolinium-enhanced MRI and diastolic dysfunction. Seventeen patients (13 men, mean age 57.7+/-9.8 years) with HCM were studied. The severity index of late gadolinium enhancement was determined by scoring the extent of enhanced tissue in 30 myocardial segments. The peak filling rate (PFR), LV ejection fraction and LV mass were determined by cine MRI. Contrast-enhanced MRI demonstrated late gadolinium enhancement in 97 of 510 segments (19%) and 13 of the 17 patients (77%). The severity index of late gadolinium enhancement demonstrated a significant negative correlation with PFR (r= -0.86, p<0.01) and with the LV ejection fraction (r= -0.59, p<0.05). No significant correlation was observed between the severity index of late gadolinium enhancement and LV mass (r=0.23, p=0.30). The extent of myocardial fibrosis revealed by late gadolinium-enhanced MRI has a strong relationship to diastolic dysfunction in patients with HCM.


Transmembrane electron transfer in diabetic nephropathy.
Erythrocytes (red blood cells [RBCs]) reduce extracellular ferricyanide by transmembrane transfer of reducing equivalents involving ascorbate recycling. Because ascorbate regeneration is glutathione (GSH) dependent and cells may be depleted of GSH in diabetes, we measured RBC GSH, plasma sulfhydryl (SH) groups, and RBC-mediated ferricyanide reduction in 30 type 1 diabetic patients (age 34 +/- 10 years, disease duration 20 +/- 8 years; no complications, n = 10; retinopathy, n = 10; nephropathy, n = 10), their 36 siblings (age 39 +/- 13 years), and matched healthy volunteers. Fasting plasma glucose was 15 +/- 7 mmol/l (vs. 5 +/- 1 in control subjects, P < 0.001), HbA1c 8.4 +/- 1.5% (vs. 5.4 +/- 0.3, P < 0.001), GSH 0.76 +/- 0.12 mg/ml packed RBCs (vs. 0.88 +/- 0.18, P < 0.01), SH groups 401 +/- 72 micromol/l (vs. 444 +/- 56, P < 0.05), and ferrocyanide generation 15 +/- 5 micromol/ml RBC per h (vs. 13 +/- 5, NS). In comparison with 10 normoalbuminuric diabetic subjects with retinopathy, 10 patients with diabetic nephropathy had similar fasting plasma glucose, HbA1c, and SH groups; lower RBC GSH (0.73 +/- 0.08 vs. 0.85 +/- 0.11, P < 0.05); and higher ferrocyanide generation (18 +/- 4 vs. 14 +/- 5, P < 0.05). The 10 patients without complications differed from the 10 healthy volunteers in glycemic control and RBC GSH. RBC electron transfer correlated with plasma lactate (r = 0.8, P = 0.01) only in the uncomplicated group. No difference was detected between siblings and healthy control subjects or between siblings of subjects in the nephropathy and retinopathy groups. Among diabetic patients, the rate of ferrocyanide generation was associated with urinary albumin excretion, plasma creatinine, and SH groups (multiple r = 0.6, P < 0.01). Transmembrane electron transfer is selectively increased in diabetic nephropathy, where RBC GSH is also depleted. The abnormality is peculiar to the nephropathy group and not contributed by familial or hereditary components because the electron flow was normal in siblings. The close relationship between cytosolic NADH and RBC electron transfer observed in diabetic patients without complications seems to be lost in the microangiopathic patients. Whereas patients with retinopathy alone still had normal activity of the RBC-reducing system, patients with nephropathy showed significantly increased activity, unrelated to metabolic parameters or plasma lactate concentration and correlated with renal function parameters and plasma thiols.


A single-dose mass balance and metabolite-profiling study of vemurafenib in patients with metastatic melanoma.
Vemurafenib, a selective inhibitor of oncogenic BRAF kinase carrying the V600 mutation, is approved for treatment of advanced BRAF mutation-positive melanoma. This study characterized mass balance, metabolism, rates/routes of elimination, and disposition of (14)C-labeled vemurafenib in patients with metastatic melanoma. Seven patients with metastatic BRAF-mutated melanoma received unlabeled vemurafenib 960 mg twice daily for 14 days. On the morning of day 15, patients received (14)C-labeled vemurafenib 960 mg (maximum 2.56 MBq [69.2 μCi]). Thereafter, patients resumed unlabeled vemurafenib (960 mg twice daily). Blood, urine, and feces were collected for metabolism, pharmacokinetic, and dose recovery analysis. Within 18 days after dose, ∽95% of (14)C-vemurafenib-related material was recovered from feces (94.1%) and urine (<1%). The parent compound was the predominant component (95%) in plasma. The mean plasma elimination half-life of (14)C-vemurafenib-related material was 71.1 h. Each metabolite accounted for <0.5% and ≤6% of the total administered dose in urine and feces, respectively (0-96 h postdose). No new metabolites were detected. Vemurafenib was well-tolerated. Excretion of vemurafenib via bile into feces is considered the predominant elimination route from plasma with minor renal elimination (<1%). e00113.


Citation counts and journal impact factors do not capture some indicators of research quality in the behavioural and brain sciences.
Citation data and journal impact factors are important components of faculty dossiers and figure prominently in both promotion decisions and assessments of a researcher's broader societal impact. Although these metrics play a large role in high-stakes decisions, the evidence is mixed about whether they are strongly correlated with indicators of research quality. We use data from a large-scale dataset comprising 45 144 journal articles with 667 208 statistical tests and data from 190 replication attempts to assess whether citation counts and impact factors predict three indicators of research quality: (i) the accuracy of statistical reporting, (ii) the evidential value of the reported data and (iii) the replicability of a given experimental result. Both citation counts and impact factors were weak and inconsistent predictors of research quality, so defined, and sometimes negatively related to quality. Our findings raise the possibility that citation data and impact factors may be of limited utility in evaluating scientists and their research. We discuss the implications of these findings in light of current incentive structures and discuss alternative approaches to evaluating research.


Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.
The novel coronavirus SARS-CoV-2 (Covid-19), spreading from Wuhan, China, is one of the causes of respiratory infections that can spread to other people through respiratory particles, and can cause symptoms such as fever, dry cough, shortness of breath, anorexia, fatigue and sore throat in infected patients. This review summarizes current strategies on the diagnosis. Additionally, treatments, infection prevention and control of the SARS-CoV-2 are addressed. In addition to the respiratory system, this virus can infect the digestive system, the urinary system and the haematological system, which causes to observe the virus in the stool, urine and blood samples in addition to throat sample. The SARS-CoV-2 causes changes in blood cells and factors and makes lung abnormalities in patients, which can be detected by serological, molecular, and radiological techniques by detecting these changes and injuries. Radiological and serological methods are the most preferred among the other methods and the radiological method is the most preferred one which can diagnose the infection quickly and accurately with fewer false-negatives, that can be effective in protecting the patient's life by initiating treatment and preventing the transmission of infection to other people.


Background parenchymal uptake on molecular breast imaging as a breast cancer risk factor: a case-control study.
Molecular breast imaging (MBI) is a functional test used for supplemental screening of women with mammographically dense breasts. Additionally, MBI depicts variable levels of background parenchymal uptake (BPU) within nonmalignant, dense fibroglandular tissue. We investigated whether BPU is a risk factor for breast cancer. We conducted a retrospective case-control study of 3027 eligible women who had undergone MBI between February 2004 and February 2014. Sixty-two incident breast cancer cases were identified. A total of 179 controls were matched on age, menopausal status, and MBI year. Two radiologists blinded to case status independently assessed BPU as one of four categories: photopenic, minimal to mild, moderate, or marked. Conditional logistic regression analysis was performed to estimate the associations (OR) of BPU categories (moderate or marked vs. minimal to mild or photopenic) and breast cancer risk, adjusted for other risk factors. The median age was 60.2 years (range 38-86 years) for cases vs. 60.2 years (range 38-88 years) for controls (p = 0.88). Women with moderate or marked BPU had a 3.4-fold (95 % CI 1.6-7.3) and 4.8-fold (95 % CI 2.1-10.8) increased risk of breast cancer, respectively, compared with women with photopenic or minimal to mild BPU, for two radiologists. The results were similar after adjustment for BI-RADS density (OR 3.3 [95 % CI 1.6-7.2] and OR 4.6 [95 % CI 2.1-10.5]) or postmenopausal hormone use (OR 3.6 [95 % CI 1.7-7.7] and OR 5.0 [95 % CI 2.2-11.4]). The association of BPU with breast cancer remained in analyses limited to postmenopausal women only (OR 3.8 [95 % CI 1.5-9.3] and OR 4.1 [95 % CI 1.6-10.2]) and invasive breast cancer cases only (OR 3.6 [95 % CI 1.5-8.8] and OR 4.4 [95 % CI 1.7-11.1]). Variable BPU was observed among women with similar mammographic density; the distribution of BPU categories differed across density categories (p < 0.0001). This study provides the first evidence for BPU as a risk factor for breast cancer. Among women with dense breasts, who comprise >40 % of the screening population, BPU may serve as a functional imaging biomarker to identify the subset at greatest risk.


[Growth assessment of children with neonatal short bowel syndrome (SBS)].
SBS is a complex entity with high morbimortality. Survival following extent intestinal resection during the neonatal period is higher than 90%. Nutritional support is paramount during the periods of high growth. To assess growth of children with neonatal SBS neonatal having received during the first two years of life. A retrospective study was done on patients assisted at the Nutrition Department of the Children's Hospital of La Plata. The following parameters were gathered: gestational age (GA), diagnosis, length of the remnant bowel, liver impairment, duration of PN and EN, and socio-economical profile of the patients. Growth assessment was done by: weight (W), height (H) at two years (Control I), and at the last follow-up visit done at the Department (Control II), using the NCHS tables. Weight and height were expressed as the Z score (Z) and the percentage of W/H, and were related to need of long-term NS. Patients were categorized into three groups according to NS requirement at the time of Control II: PN-dependent, EN-dependent, and those not requiring nutritional support (WOS). Eighteen patients were included. Length of the remnant bowel was: 45 cm. (r 10-80 cm.), length was < 40 cm in 11 pts. (61%) (massive resection). The ileocecal valve was resected in 9 pts. (50%) and 3 pts. (16 %) required partial colon resection and 2 pts. (11%) total resection. Mean Z scores for W/A, H/A, %W/H, Z W/H yielded values < -2 SD, and the percentage of W/H appropriateness was > 90% in both controls. Twenty seven percent of the patients at two years of age, and 33% at the last control showed height < -2 SD. Two patients (11%) died while on PN from liver failure, both with 10 cm of remnant bowel and without VIC. At Control II, 4 patients (22%) remained PN-dependent. Mean length of the remnant bowel in this group was 33 cm (r: 17-50) and mean follow-up duration with PN was 2176 days (r: 750-4380). Six patients (33%) remained EN-dependent at Control II, with a mean intestinal length of 41 cm (r: 20-75) and 2 out of 6 pts. did not have VIC. This group of patients required PN as the initial therapy with a mean duration of 629 days. Follow-up time while on EN was 627 days (r: 210-3010). Six patients (33%) achieved nutritional support independence (WOS) with a mean intestinal length of 60 cm (r: 27-80) after a mean duration of NS of 791 days, being assisted with dietary recommendations and vitamins and minerals supplementation. The group showing the greatest growth impairment was the EN-dependent group since we consider that early withdrawal of PN was decided based on inappropriate socio-environmental conditions. According to the present study, we conclude that is may be possible to achieve a normal growth in children with neonatal SBS under nutritional support and that complications related to this nutritional therapy or difficulties for adequately implementing it at home may affect the final height.


Dansylarginine N-(3-ethyl-1.5-pentanediyl)amide. A potent and selective fluorescent inhibitor of butyrylcholinesterase.
Interactions between dansylarginine N-(3-ethyl-1,5-pentanediyl)amide (DAPA) and the cholinesterases were examined by the techniques of enzyme kinetics and fluorescence spectroscopy. When tested with partially purified enzyme preparations, DAPA was a potent inhibitor of butyrylcholinesterase (IC50 = 2 x 10(-7) M) but not of acetylcholinesterase (IC50 = 4 x 10(-4) M). For a detailed study of the effects of DAPA on butyrylcholinesterase (BuChE), the enzyme was purified to homogeneity from horse serum, with the aid of affinity chromatography on N-methyl acridinium. The kinetics of the inhibition of purified BuChE by DAPA were complex, having both competitive and non-competitive features, and it was not possible to estimate Ki unambiguously. Spectroscopic measurements showed that the fluorescence of the dansyl moiety was strongly affected by the binding to BuChE. With excitation at 330 nm, total fluorescence emission from bound DAPA (at 450 nm and above) was 21-fold greater than from free DAPA. In a titration experiment, this enhancement of fluorescence intensity was used to calculate that each monomer of BuChE has two apparently independent DAPA-binding sites with a Kd of 4.5 x 10(-7) M. Further measurements showed that the fluorescence emission of bound DAPA was markedly blue-shifted (to 502 nm from 570 nm in free solution) and that the fluorescence lifetime of this form was greatly prolonged (to 24 nsec from 2.7 nsec). These observations indicate that the high affinity binding sites on BuChE lock DAPA in a highly non-polar environment.


[Is there an association between psychological stress and request for caesarian section?].
Caesarean section rates have increased in Norway, as in the rest of the western world since the beginning of the 1970s, and further explanations are needed to understand this development. The study aimed to examine whether demographic or psychological burdens differed among women who feared childbirth, according to whether or not they requested caesarean section. In the period 2000-02, 164 pregnant women who feared childbirth were referred for counselling with two midwives (specialized in mental health) at the antenatal clinic at the University Hospital of North Norway. Data were retrieved from counselling sessions, referral letters, antenatal and intrapartum care records. The group that wished to have caesarean sections (n = 86) was compared with the one that did not (n = 78). 80% of the women had previously experienced anxiety and/or depression, 32% had eating disturbances and 72% reported having been abused. In the group requesting caesarean section the women had more severe fear of childbirth, previous traumatic birth experiences, previous anxiety and depression, lack of confidence in the professional staff and fewer had been treated for their psychological problems. At the onset of labour, 86% who initially requested a caesarean delivery were prepared for a vaginal birth. The overall caesarean rate for both groups was 32%. The women who feared childbirth generally had a larger burden of psychosocial and psychiatric problems than others, and those who requested a caesarean delivery had most. Charting and processing these burdens is presumably of significance for the birth outcome.


HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread.
HIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, we developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. We discovered HIV-1-induced activation of signaling networks during viral spread encompassing over 200 cellular proteins. Strikingly, pathways downstream of the T cell receptor were the most significantly activated, despite the absence of canonical antigen-dependent stimulation. The importance of this pathway was demonstrated by the depletion of proteins, and we show that HIV-1 Env-mediated cell-cell contact, the T cell receptor, and the Src kinase Lck were essential for signaling-dependent enhancement of viral dissemination. This study demonstrates that manipulation of signaling at immune cell contacts by HIV-1 is essential for promoting virus replication and defines a paradigm for antigen-independent T cell signaling.


Addressing challenges to human health in the Anthropocene epoch-an overview of the findings of the Rockefeller/Lancet Commission on Planetary Health.
The report of the Rockefeller Foundation/Lancet Commission on Planetary Health described how human health directly depends upon the environment. It takes a broad perspective not only acknowledging climate change as the most important global environmental threat to health but also recognizing other impacts, including dramatic loss of tropical forests, land degradation, loss of biodiversity, declining freshwater resources, ocean acidification, and over-exploitation of fisheries. All pose challenges to human health gains, leading to the concept of planetary health-that the human condition is tied to natural systems. The Planetary Health Commission report highlights several major concerns arising from environmental change including impacts on food availability and quality, increases in natural disasters and population displacement, and newly emerging diseases, e.g. from zoonotic infections. Three challenges emerge from the report: the first is imagination, or conceptual challenges-better metrics are needed to assess human progress within the context of environmental change; the second is a lack of relevant knowledge, requiring more research on the inter-linkages between environmental change and health and on the effectiveness of potential solutions; and the third is implementation of solutions, ensuring that the science is translated into policy and practice. There are many opportunities to promote planetary health including developing sustainable and healthy cities, encouraging more resilient health systems and disaster preparedness, reducing food waste, preserving ecosystems, and redirecting harmful subsidies in food, agriculture, fishery and energy sectors. Many current trends are driven by inequitable, inefficient, and unsustainable patterns of resource consumption and technological development, coupled with population growth, but solutions lie within reach. Prosperity must be redefined as an enhancement of the quality of life and the delivery of improved health for all, together with respect for natural systems.


Expression pattern of androgen receptors, AR-V7 and AR-567es, in circulating tumor cells and paired plasma-derived extracellular vesicles in metastatic castration resistant prostate cancer.
Androgen-receptor splice variant 7 (AR-V7) is a highly promising liquid biopsy predictive biomarker showing primary or acquired resistance to novel androgen receptor signaling inhibitors in metastatic castration resistant prostate cancer (mCRPC). We present for the first time the expression pattern of AR-FL, AR-V7, and AR-567es at a quantitative level in circulating tumor cells (CTCs) and paired plasma-derived extracellular vesicles in mCRPC. We first developed and analytically validated a novel multiplex RT-qPCR assay for AR full length (AR-FL), AR-V7, AR-567es and AR-total. We then quantified the expression levels of AR-splice variants, CK-19 (epithelial marker) and B2M (reference gene) in EpCAM+ CTCs, and paired plasma-derived extracellular vesicles isolated from peripheral blood (20 mL) of 62 mCRPC patients and 10 healthy donors. CTCs were enumerated using the FDA-cleared CellSearch® system. In CTCs AR-FL was detected in 64/69 (92.3%), AR-V7 in 34/69 (49.3%), AR-567es in 16/69 (23.2%) and AR-total in 62/69 (89.9%). In 52 out of 69 samples, paired plasma-derived extracellular vesicles were analyzed. AR-FL was detected in 40/52 (76.9%), AR-V7 in 4/52 (7.7%), AR-567 in 2/52 (3.8%) and AR total in 39/52 (75.0%). In all cases AR splice variants were expressed in higher levels in CTCs than in paired extracellular vesicles, while AR-V7 was detected in higher percentages than in AR-567es. Using CellSearch®, CTCs were detected in 52/69 (75.4%) mCRPC patient samples; 27/52 (51.9%) of these samples were CTC+/AR-V7+ and 14/52 (26.9%) were CTC+/AR-567es+, while 7/17 (41.2%) were CTC-/AR-V7+ and 2/17 (11.8%) were CTC-/AR-567es+. Our results reveal for the first time a remarkable heterogeneity in the expression levels of AR-FL, AR-V7 and AR-567es in EpCAM+ CTCs and paired extracellular vesicles between individual mCRPC patients. The clinical significance of this finding will be further investigated in a large patient cohort with respect to therapy response.


Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications.
The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0-87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI.


Tenascin-R is a functional modulator of sodium channel beta subunits.
Voltage-gated sodium channels isolated from mammalian brain are composed of alpha, beta1, and beta2 subunits. The alpha subunit forms the ion conducting pore of the channel, whereas the beta1 and beta2 subunits modulate channel function, as well as channel plasma membrane expression levels. beta1 and beta2 each contain a single, extracellular Ig-like domain with structural similarity to the neural cell adhesion molecule (CAM), myelin Po. beta2 contains strong amino acid homology to the third Ig domain and to the juxtamembrane region of F3/contactin. Many CAMs of the Ig superfamily have been shown to interact with extracellular matrix molecules. We hypothesized that beta2 may interact with tenascin-R (TN-R), an extracellular matrix molecule that is secreted by oligodendrocytes during myelination and that binds F3-contactin. We show here that cells expressing sodium channel beta1 or beta2 subunits are functionally modulated by TN-R. Transfected cells stably expressing beta1 or beta2 subunits initially recognized and then were repelled from TN-R substrates. The cysteine-rich amino-terminal domain of TN-R expressed as a recombinant peptide, termed EGF-L, appears to be responsible for the repellent effect on beta subunit-expressing cells. The epidermal growth factor-like repeats and fibronectin-like repeats 6-8 are most effective in the initial adhesion of beta subunit-expressing cells. Application of EGF-L to alphaIIAbeta1beta2 channels expressed in Xenopus oocytes potentiated expressed sodium currents without significantly altering current time course or the voltage dependence of current activation or inactivation. Thus, sodium channel beta subunits appear to function as CAMs, and TN-R may be an important regulator of sodium channel localization and function in neurons.